PHARMACOTHERAPY SELF-ASSESSMENT PROGRAM

2025 ▪ BOOK 1

Cardiology

SERIES EDITORS

Cynthia A. Sanoski, Pharm.D., FCCP, BCPS

Daniel M. Witt, Pharm.D., FCCP, BCPS ®
 PHARMACOTHERAPY SELF-ASSESSMENT PROGRAM

PSAP Series Editors

Cynthia A. Sanoski, Pharm.D., FCCP, BCPS, Associate Dean of Student Affairs and Professor
of Instruction, University of Iowa College of Pharmacy, Iowa City, Iowa

Daniel M. Witt, Pharm.D., FCCP, BCPS, Professor and Chair, Department of

Pharmacotherapy, Assistant Dean of Clinical Affairs, University of Utah College of Pharmacy,
Salt Lake City, Utah

The PSAP Series Editors design each year’s releases by drawing from the domains, tasks, and knowledge statements in the BPS
Pharmacotherapy Specialist Certification Content Outline/Classification System. Working with a Faculty Panel Chair (guest editor), the
Series Editors refine the list of chapters and features so that only the most relevant topics are updated in each release. Members of the
faculty panel collaborate on the content outline for each chapter and feature, ensuring a complete review of published evidence on
that clinical topic. Generalist BCPS reviewers join the editorial process to enhance the material’s appropriateness for the recertifying
audience. The result is an evidence-based update that can be used to self-assess clinical skills and improve patient outcomes.

New for 2025!

• Second-Chance Posttest Option Visit the ACCP Store at
• Complete single chapters/features for credit [Link]/store

Recertification ACPE Minimum

PSAP Release Content Planned Release Date
Deadline Deadline Hours
PSAP 2025 Book 1 Cardiology Jan. 15, 2025 Jul. 15, 2025 Jan. 15, 2028 12.0

PSAP 2025 Book 2 Geriatrics May 15, 2025 Nov. 14, 2025 May 15, 2028 12.0

Behavioral Health and

PSAP 2025 Book 3 Sep. 15, 2025 Mar. 13, 2026 Sep. 15, 2028 12.0
Pediatrics

Endocrinology and
PSAP 2026 Book 1 Jan. 15, 2026 Jul. 15, 2026 Jan. 15, 2029 12.0
Nephrology

Critical Care/
PSAP 2026 Book 2 May 15, 2026 Nov. 13, 2026 May 15, 2029 12.0
Emergency Medicine

Pulmonary and
PSAP 2026 Book 3 Sep. 15, 2026 Mar. 15, 2027 Sep. 15, 2029 12.0
Gastrointestinal

PSAP 2027 Book 1 Infectious Diseases Jan. 15, 2027 Jul. 15, 2027 Jan. 15, 2030 12.0

Hematology and
PSAP 2027 Book 2 May 17, 2027 Nov. 17, 2027 May 17, 2030 12.0
Oncology

Neurology and
PSAP 2027 Book 3 Sep. 15, 2027 Mar. 15, 2028 Sep. 15, 2030 12.0
Chronic Diseases

ACCP’s Self-Assessment Programs are home study series that provide clinical
pharmacists with pertinent therapeutic updates to enhance their practice skills
and improve patient outcomes.
The American College of Clinical Pharmacy is approved by BPS as a provider for the
recertification of BCPS. ®
IMPORTANT INFORMATION ON THE RELEASE
OF PSAP 2025 Book 1 (Cardiology)

Book Formats and Content

Online book: All purchasers of this PSAP release have access to the online book (interactive PDFs). To access, go to [Link].
com and sign into your My Account page using your e-mail address and password (technical assistance is available). Scroll down
to find your book and the required posttests under My Products. The online book can be saved to the desktop or printed. The lat-
est version of Adobe Acrobat Reader (available free) offers functionality such as highlighting or adding “sticky notes” to the text.

E-Media book: All purchasers also have access to the e-media version. Follow these instructions to load the text and
self-assessment questions in this book onto your e-reader, tablet, or Android phone.

PSAP Audio Companion: All purchasers also have access to the PSAP Audio Companion. Follow these instructions to load these
files onto an MP3 player.

Print books: If you have purchased a print version of this book, it will be delivered on or near the release date to the address of
record on your ACCP account. If you have not received the print book within 1 week of the release date, contact customer service
by e-mailing accp@[Link]. NOTE: The online book may be updated after the print book goes to press. Before submitting a
posttest, please check the online errata ([Link] for the presence of updates.

Hyperlinks: To facilitate further learning and research, this publication incorporates hyperlinks to websites administered by other
organizations. Internal and external hypertext links are visible as underlined text in the print book and are active in the Online and
e-Media versions of the book. NOTE: ACCP assumes no liability for material downloaded from or accessed on these websites.

Abbreviations, Laboratory Values: At the start of each chapter/feature are hyperlinks to tables with selected medical abbrevi-
ations and reference ranges for common laboratory tests. These tables can be used as a resource in reading the material and
completing the self-assessment questions.

NOTE: The editors and publisher of PSAP recognize that the development of this volume of material offers many opportunities for
error. Despite our best efforts, some errors may persist into publication. Drug dosage schedules are, we believe, accurate and in
accordance with current standards. Readers are advised, however, to check package inserts for the recommended dosages and
contraindications. This is especially important for new, infrequently used, and highly toxic drugs.
Director, Professional Development and Marketing: Joanna Gillette, B.A.
Director, ACCP Career Development Programs: Keri A. Sims, Pharm.D., BCPS
Senior Managing Editor: Edward Alderman, B.S., B.A.
Managing Editor: Peter Burns, B.A.
Senior Medical Editor: Kimma Sheldon-Old, Ph.D.
Director, Information Technology: Brent Paloutzian, A.A.S.

For ordering information or questions, e-mail: accp@[Link]

PSAP 2025 Book 1 (Cardiology)

Library of Congress Control Number: 2025930128
ISBN-13s: 978-1-964074-14-6 (print); 978-1-964074-15-3 (eBook)

Print versions are produced in the United States of America.

To cite PSAP properly:

Chapter authors. Chapter name. In: Sanoski CA, Witt DM, eds. Pharmacotherapy Self-Assessment Program, 2025 Book 1.
Cardiology. Lenexa, KS: American College of Clinical Pharmacy, 2025:page range.

PSAP™ is a registered trademark of the American College of Clinical Pharmacy.

Pharmacotherapy
Self-Assessment
Program

Copyright ©2025 by the American College of Clinical Pharmacy. All rights reserved. This book is protected by copyright. No part of
this publication may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic or mechan-
ical, including photocopy, without prior written permission of the American College of Clinical Pharmacy. NOTE: Purchasers of this
ACCP product may have one copy of the PDF printed for their personal educational use.
Continuing Pharmacy Education
and Recertification Instructions
TESTING

Book Release Date: January 15, 2025

BCPS test deadline: 11:59 p.m. (Central) on July 15, 2025
ACPE test deadline: 11:59 p.m. (Central) on January 14, 2028

Before submitting a posttest: Check the online errata for any changes or updates to this Pharmacotherapy Self-Assessment
Program release. You may complete one or all available elements for credit. Submitting a required posttest for BCPS recertifica-
tion attests that you have completed the test as an individual effort and not in collaboration with any other individual or group.
Failure to complete this test as an individual effort may jeopardize your ability to use PSAP for BCPS recertification.

PSAP Target Audience: The target audience for PSAP 2025 Book 1 (Cardiology) is pharmacotherapy specialists and advanced-
level clinical pharmacists whose practice involves treating patients with cardiovascular conditions commonly seen in outpatient
and inpatient settings as well a preventive health and patient monitoring.

Available CPE credits: Purchasers who successfully complete all posttests for PSAP 2025 Book 1 (Cardiology) can earn 18.5
contact hours of CPE credit. The universal activity numbers are as follows:

Learning Activity ACPE Activity Number CPE Hrs

Chapter: Hypertension 0217-0000-25-010-H01-P 2.0

Chapter: Complex Lipid Management 0217-0000-25-011-H01-P 2.0

Recorded Webcast: Behavioral Approaches to Optimize Patient Engagement 0217-0000-25-012-H01-P 1.5

in a Healthy Lifestyle

Chapter: Heart Failure with Preserved Ejection Fraction 0217-0000-25-013-H01-P 2.0

Chapter: Transitions of Care After Acute Coronary Syndrome 0217-0000-25-014-H01-P 2.0

Case Series: Orthostatic Hypotension 0217-0000-25-015-H01-P 2.0

Chapter: Venous Thromboembolism: Primary Prevention 0217-0000-25-016-H01-P 2.5

Chapter: Antithrombotic Therapy for Valvular Heart Disease 0217-0000-25-017-H01-P 2.5

Chapter: ECG Interpretation and Management of QT Prolongation 0217-0000-25-018-H01-P 2.0

TO EARN CPE CREDITS FROM THIS PSAP BOOK

Posttest access: Go to [Link] and sign in with your e-mail address and password. Technical support is available from
8 a.m. to 5 p.m. (Central) weekdays by calling (913) 492-3311. PSAP products are listed under My Products on your My Account
page.

BCPS Recertification Credit: To receive BCPS recertification credit, a PSAP posttest must be submitted within the
6-month period after the book’s release (see above). Only completed tests are eligible for credit; no partial or incom-
plete tests will be processed. You may complete one or all available learning activities for credit.

The passing point to earn BCPS recertification credit is based on an expert analysis of the assessment items in each posttest
module. Any posttest submitted before the BCPS test deadline that meets this passing point will earn BCPS recertification credits.
These credits will be assigned as of the date of test submission and reported within 48 hours to BPS. For statements of recertifica-
tion credit, visit [Link].

Remediation: In accordance with BPS guidelines concerning remediation for products launched in 2024 and after, posttests that
do not reach the passing point for recertification credit will generate a second-chance test option. This test will automatically
appear in the learner’s My Account page and will have assessment items presented in a different order. To qualify for recertifica-
tion credit, the second-chance test must be submitted before the recertification posttest deadline stated above.

BCPS Recertification: The ACCP Recertification Dashboard is a free online tool that can track recertification credits as they are
earned through ACCP and schedule new opportunities for credits from upcoming ACCP professional development programs.
Questions regarding the number of hours required for BCPS recertification should be directed to BPS at [Link].

ACPE CPE Credit: To receive ACPE CPE credit for a PSAP module, a posttest must be submitted within 3 years after the book’s
release (see above). Only completed tests are eligible for credit; no partial or incomplete tests will be processed. You may complete
one or all available learning activities for credit. Any posttest submitted before the ACPE deadline that scores 50% or greater will be
awarded the appropriate CPE. These credits will be assigned as of the date of test submission and reported within 48 hours. For
statements of CPE credit, visit [Link].

Posttest answers: The explained answers for each learning activity – with rationale and supporting references – will be posted
2 weeks after the recertification posttest deadline and will be available on the My Account page to anyone who has either (1)
submitted a posttest or (2) waived the right to receive credit from a posttest. Go to [Link] and sign in with your e-mail
address and password. By completing the waiver form, you waive the opportunity to receive CPE credit for that module.

Continuing Pharmacy Education (CPE) Credit: The American College of Clinical Pharmacy is accredited by the
Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education.

The American College of Clinical Pharmacy is approved by BPS as a provider for the
recertification of BCPS.

BPS is an autonomous division of the American Pharmacists Association. To maintain its strict, inde-
pendent standards for certification, BPS does NOT endorse or provide review information, preparatory
courses, or study guides for board certification examinations. BPS, through its specialty councils, is
responsible for specialty examination content, administration, scoring, and all other aspects of its
certification programs. BPS is totally separate and distinct from ACCP. For information about BPS spe-
cialty recertification the BPS recertification process, go to: [Link]
PSAP 2025 Book 1 (Cardiology) Faculty Panel
Series Editors: Faculty Panel Chair:
Cynthia A. Sanoski, Pharm.D., FCCP, BCPS Nicholas W. Carris, Pharm.D., FCCP, BCPS
Associate Dean of Student Affairs Associate Professor
Professor of Instruction Department of Pharmacotherapeutics and Clinical Research
University of Iowa College of Pharmacy University of South Florida
Iowa City, Iowa Taneja College of Pharmacy
Daniel M. Witt, Pharm.D., FCCP, BCPS Tampa, Florida

Professor and Chair

Department of Pharmacotherapy
Assistant Dean of Clinical Affairs
University of Utah College of Pharmacy
Salt Lake City, Utah

Disclosures: ACCP Staff/Series Leaders

Consultancies: Daniel Witt (Roche Diagnostics)
Grants: Daniel Witt (Agency for Health Research and Quality, Roche Diagnostics)
Nothing to disclose: Ed Alderman, Peter Burns, Joanna Gillette, Brent Paloutzian, Cynthia Sanoski, Kimma Sheldon-Old, Keri Sims

Note: All relevant financial relationships listed for these individuals have been mitigated.

Note: Any views, thoughts, or opinions expressed by authors and reviewers in this publication do not necessarily reflect
the faculty member’s employer, organization, committee, or other group or individual.

Learning Activity Authors Reviewers Disclosures

Chapter: Hypertension Andrew Y. Hwang, Pharm.D., Rachel W. Khan, Pharm.D., BCPS Andrew Y. Hwang: Nothing to
BCPS Associate Professor disclose
Associate Professor Department of Pharmacotherapy Christina Helms Sherrill:
Department of Pharmacy & Outcomes Science Nothing to disclose
Practice Virginia Commonwealth Rachel W. Khan: Nothing to
Massachusetts College of University School of Pharmacy disclose
Pharmacy and Health Sciences Richmond, Virginia Samira Zantout: Nothing to
Boston, Massachusetts disclose
Samira Zantout, Pharm.D., Jessica Reno: Nothing to
Christina H. Sherrill, Pharm.D., BCPS, BCIDP, AAHIVP disclose
BCACP, BC-ADM Antimicrobial Stewardship/
Teaching Associate Professor Infectious Diseases Pharmacist
Division of Practice Department of Pharmacy
Advancement and Clinical Avera McKennan Hospital &
Education University Health Center
University of North Carolina Sioux Falls, South Dakota
Eshelman School of Pharmacy
Asheville, North Carolina Jessica Reno, BSN, Pharm.D.,
RN-BC, BCPS
Cardiology Clinical Pharmacy
Specialist
Heart, Vascular, and Thoracic
Institute
Cleveland Clinic
Cleveland, Ohio
Learning Activity Authors Reviewers Disclosures

Chapter: Complex Lipid Maria C. Coyle, Pharm.D., FCCP, Michael S. Kelly, Pharm.D., Maria C. Coyle: Consultancies
Management BCPS, BCACP, CLS FNLA, BCACP (Ohio Pharmacists Association,
Associate Clinical Professor Associate Professor FDA Non-Prescription
College of Pharmacy Department of Pharmacy Drug Advisory Committee):
The Ohio State University Practice Honoraria (Pharmacy Times
Specialty Practice Pharmacist Jefferson College of Pharmacy CE, ACCP/ASHP)
Ambulatory Care Philadelphia, Pennsylvania Erica Davidson: Nothing to
The Ohio State University disclose
Wexner Medical Center Rebecca Tran, Pharm.D., BCPS, Michael S. Kelly: Nothing to
Columbus Ohio BCACP, BCCP, CLS disclose
Associate Professor Rebecca Cheung Tran: Nothing
Erica Davidson, Pharm.D., Department of Pharmacy to disclose
BCACP, CLS, ACE Practice and Administration Kellie J. Goodlet: Honoraria
Specialty Practice Pharm Lead, Western University of Health (Merck)
Ambulatory Care Sciences College of Pharmacy
Department of Pharmacy Pomona, California
The Ohio State University
Wexner Medical Center Kellie J. Goodlet, Pharm.D.,
Columbus, Ohio BCIDP, BCPS, BCTXP
Associate Professor
Department of Pharmacy
Midwestern University College
of Pharmacy
Glendale, Arizona
Recorded Webcast: Lauren M. Hynicka, Pharm.D., Jason Isch, Pharm.D., BCACP Lauren M. Hynicka:
Behavioral Approaches BCPS Associate Professor of Pharmacy Consultancies (LexiComp);
to Optimize Patient Associate Professor Practice Grants (University of Maryland
Engagement in a University of Maryland School of Ambulatory Care Baltimore, Department of
Healthy Lifestyle Pharmacy Manchester University Health and Mental Hygiene);
Baltimore, Maryland South Bend, Indiana Honoraria (PharmCon/Free CE,
AZO)
Richard J. Rovelli, Pharm.D., Janet M. Bramell, Pharm.D., Richard J. Rovelli: Nothing to
BCCP BCPS, BCOP disclose
Cardiology Clinical Pharmacy Clinical Pharmacy Practitioner, Jason Isch: Nothing to disclose
Specialist Hematology/Oncology Janet Bramell: Nothing to
Department of Pharmacy Department of Pharmacy disclose
University of Maryland Medical VA Tennessee Valley Healthcare Richard Chan: Nothing to
Center System disclose
Baltimore, Maryland Nashville, Tennessee

Richard Chan, Pharm.D., BCPS

Assistant Professor, Pharmacy
Practice
Northeast Ohio Medical
University
Rootstown, Ohio
Internal Medicine Clinical
Pharmacy Specialist
University Hospitals Portage
Medical Center
Ravenna, Ohio
Learning Activity Authors Reviewers Disclosures

Chapter: Heart Failure Aimon C. Miranda, Pharm.D., Sandeep Devabhakthuni, Aimon C. Miranda: Grants (USF
with Preserved BCPS Pharm.D., BCCP Center of Innovative Teaching
Ejection Fraction Associate Professor Safety Evaluator and Learning, University of
Coordinator of Clinical Informatics Center for Drug Evaluation and South Florida)
Department of Research Office of Surveillance Cyrille K. Cornelio: Grants
Pharmacotherapeutic and and Epidemiology Division of (ACCP Ambulatory Care PRN)
Clinical Research Pharmacovigilance I Sandeep Devabhakthuni:
University of South Florida US Food and Drug Nothing to disclose
Taneja College of Pharmacy Administration Patrick Roland: Nothing to
Tampa, Florida Silver Springs, Maryland disclose
Jennifer Polyniak: Nothing to
Cyrille K. Cornelio, Pharm.D., Patrick D. Roland, Pharm.D., disclose
BCCP BCPS
Assistant Professor Clinical Pharmacist
Department of Inpatient Pharmacy
Pharmacotherapeutics and Baptist Health Hardin
Clinical research Elizabethtown, Kentucky
University of South Florida
Health Taneja College of Jennifer L. Polyniak, Pharm.D.,
Pharmacy BCPS, BCCCP
Tampa, Florida Pharmacist II
Department of Pharmacy
Sharp Memorial Hospital
San Diego, California
Chapter: Transitions Joel C. Marrs, Pharm.D., MPH, Eric A. Dietrich, Pharm.D., Joel C. Marrs: Consultancies
of Care After Acute FAHA, FASHP, FCCP, FNLA, BCACP, CPC, CPB, CEMC (Board of Pharmacy
Coronary Syndrome BCACP, BCCP, BCPS Specialties), American
Professor Paul M. Boylan, Pharm.D., BCPS Association of Clinical
Department of Clinical Associate Professor Endocrinology [two
Pharmacy & Translational Department of Pharmacy: consultancies])
Science Clinical and Administrative Eric A. Dietrich: Nothing to
University of Tennessee Health Sciences disclose
Science Center College of University of Oklahoma Health Paul Boylan: Consultancies
Pharmacy Sciences College of Pharmacy (National Transitions of Care
Nashville, Tennessee Oklahoma City, Oklahoma Coalition); Stock Ownership
(Lilly); Grants (Pfizer);
Shereen Ahmad Dasuqi, MSc. Honoraria (iCare Pharmacy
Pharm., BCPS, BCCCP Services Inc.)
Critical Care Clinical Pharmacist Shereen Dasuqi: Nothing to
Pharmacy Department disclose
King Saud University Medical
City
Riyadh, Saudi Arabia
Learning Activity Authors Reviewers Disclosures

Case Series: Elizabeth Pogge, Pharm.D., Anthony Ishak, Pharm.D., BCPS Elizabeth Pogge: Consultancies
Orthostatic MPH, FASCP, FAzPA, BCPS, Clinical Pharmacist (Sanofi)
Hypotension BCGP Department of Pharmacy Anthony Ishak: Nothing to
Professor Massachusetts General Hospital disclose
Department of Pharmacy Boston, Massachusetts Arlene Thomas: Nothing to
Practice disclose
Midwestern University College Arlene Thomas, Pharm.D., BCPS Olga Hilas: Consultancies
of Pharmacy - Glendale Campus Transitions of Care Pharmacist (Fidelis Care NY/Centene)
Glendale, Arizona Pharmacy Department
Memorial Hermann Greater
Heights Hospital
Houston, Texas

Olga Hilas, Pharm.D., MPH,

FASCP, BCPS, BCGP
Professor
Department of Pharmacy
Practice
St. John’s University
College of Pharmacy and Health
Sciences
Queens, New York
Chapter: Venous Allison E. Burnett, Pharm.D., Gabriel V. Fontaine, Pharm.D., Allison E. Burnett:
Thromboembolism: CACP MBA, FNCS, FCCM, BCPS, (Anticoagulation Forum,
Primary Prevention Antithrombosis Stewardship BCCCP National Certification Board
Pharmacist Clinical Pharmacy Manager for Anticoagulation Providers);
Inpatient Pharmacy Clinical Pharmacist Royalties (Up to Date)
University of New Mexico Associate Professor of Kathryn E. Dane: Consultancies
Hospital Neurosciences, Critical Care, and (Wolters Kluwer)
Albuquerque, New Mexico Emergency Medicine Gabriel Fontaine: Consultancies
Departments of Pharmacy and (AstraZeneca, Chiesi,
Kathryn E. Dane, Pharm.D., Neurosciences Anticoagulation Forum); Grants
BCPS Intermountain Medical Center, (Anticoagulation Forum);
Clinical Pharmacy Specialist, Intermountain Health Honoraria (AstraZeneca,
Benign Hematology and Salt Lake City, Utah Chiesi, Anticoagulation Forum)
Cardiology Grace Barr: Nothing to disclose
Co-Director, Hemostatic and Grace Barr, Pharm.D., BCPS Abby Gallagher: Nothing to
Antithrombotic Stewardship Assistant Professor of Pharmacy disclose
Program Practice
Department of Pharmacy Campbell University College of
The Johns Hopkins Hospital Pharmacy & Health Sciences
Baltimore, Maryland Buies Creek, North Carolina

Abby Gallagher, Pharm.D., BCPS

Drug Information Clinical
Pharmacist
Cleveland Clinic
Cleveland, Ohio
Learning Activity Authors Reviewers Disclosures

Chapter: Antithrombotic Kelly M. Rudd, Pharm.D., FCCP, Toby Trujillo, Pharm.D., FCCP, Kelly M. Rudd: Consultancies
Therapy for Valvular BCPS, CACP FAHA, BCPS (Wolters Kluwer)
Heart Disease Clinical Associate Professor of Professor Amanda Winans: Consultancies
Medicine Department of Clinical (Bristol Myers Squibb)
Department of Medical Pharmacy Toby C. Trujillo: Nothing to
Education University of Colorado Skaggs disclose
Oklahoma State University School of Pharmacy and Ahmed A Shible: Nothing to
Center for Health Sciences Pharmaceutical Sciences disclose
College of Osteopathic Medicine Aurora, Colorado Jenna Januszka: Nothing to
Tulsa, Oklahoma disclose
Ahmed A Shible, Pharm.D.,
Amanda R. McFee Winans, BCPS, BCCCP
Pharm.D., BCPS, CACP Clinical Pharmacy Coordinator
Clinical Pharmacy Specialist – Cardiology, Critical Care, and
Clinical Pharmacy Supervisor Neurology
Department of Pharmaceutical Department of Pharmacy
Care Services UNC Health Rex
Bassett Medical Center Raleigh, North Carolina
Cooperstown, New York
Jenna Januszka, Pharm.D., CPP,
BCPS, AAHIVP
Clinical Pharmacist
Practitioner– HIV/OPAT
Duke University Hospital
Durham, North Carolina
Chapter: ECG Zachary R. Noel, Pharm.D., Jessica Carey, Pharm.D. Zachary Noel: Nothing to
Interpretation and Ph.D., BCCP Assistant Clinical Professor disclose
Management of QT Associate Professor College of Pharmacy Joseph Van Tuyl: Nothing to
Prolongation Department of Practice University of Utah disclose
Advancement and Clinical Salt Lake City, Utah Jessica Carey: Nothing to
Education disclose
UNC Eshelman School of Cathryn C. McIntosh, Pharm.D., Cathryn McIntosh: Nothing to
Pharmacy BCPS, BCCP disclose
Chapel Hill, North Carolina Clinical Pharmacist Emily Kostelic: Nothing to
Department of Pharmacy disclose
Joseph S. Van Tuyl, Pharm.D., VA St. Louis Health Care
BCCP System- John Cochran Division
Associate Professor St. Louis, Missouri
Department of Pharmacy
Practice Emily Moose Kostelic, Pharm.D.,
St. Louis College of Pharmacy BCPS
at UHSP Internal Medicine Clinical
St. Louis, Missouri Pharmacist
Department of Pharmacy
Atrium Health Wake Forest
Baptist
Winston-Salem, North Carolina
TABLE OF CONTENTS
Hypertension Emerging Therapies ������������������������������������������������������������������������� 72

By Andrew Y. Hwang, Pharm.D., BCPS; and Christina H. Sherrill, Medications with No Added Benefit in HFpEF ����������������������������� 73
Pharm.D., BCACP, BC-ADM Management of Comorbidities ������������������������������������������������������� 74
Introduction������������������������������������������������������������������������������������������� 1 Nonpharmacologic Management and Preventive Care ��������������� 78
Evaluation of Hypertension ��������������������������������������������������������������� 2 Remote Monitoring in HFpEF ��������������������������������������������������������� 79
Clinical Guideline Update ������������������������������������������������������������������� 4 Referral to Cardiology or HF Specialist ����������������������������������������� 79
Treatment Goals ��������������������������������������������������������������������������������� 5 Conclusion ����������������������������������������������������������������������������������������� 80
Hypertension Management ��������������������������������������������������������������� 7 References ����������������������������������������������������������������������������������������� 80
Hypertensive Crisis ��������������������������������������������������������������������������� 15 Self-Assessment Questions������������������������������������������������������������� 86
Resistant and Refractory Hypertension ��������������������������������������� 16
Conclusion ����������������������������������������������������������������������������������������� 17 Transitions of Care After Acute Coronary
Syndrome
References ����������������������������������������������������������������������������������������� 18
By Joel C. Marrs, Pharm.D., MPH, FAHA, FASHP, FCCP, FNLA, BCACP,
Self-Assessment Questions������������������������������������������������������������� 23
BCCP, BCPS

Introduction ��������������������������������������������������������������������������������������� 91
Complex Lipid Management
General Approach to Treatment Decisions ����������������������������������� 92
By Maria C. Coyle, Pharm.D., FCCP, BCPS, BCACP, CLS; and Erica
Davidson, Pharm.D., BCACP, CLS, ACE Key Guideline Recommendations for Reducing Risk Factors for
Chronic Diseases After an ACS Event ������������������������������������������� 93
Introduction ��������������������������������������������������������������������������������������� 27
Guideline-Directed Management and Therapy (GDMT) After ACS
Challenges in Optimizing Care ������������������������������������������������������� 27 and Transition to Ambulatory Care ������������������������������������������������� 94
Current Approach to Risk Assessment and Treatment Targets � 33 Special Patient Populations After ACS ����������������������������������������� 97
Complex Lipid Management ����������������������������������������������������������� 39 TOC and Pharmacist Care of Patients After ACS ����������������������� 100
Pharmacist Care of Patients with Complex Dyslipidemia ����������� 44 Conclusion ��������������������������������������������������������������������������������������� 102
Conclusion ����������������������������������������������������������������������������������������� 49 References ��������������������������������������������������������������������������������������� 102
References ����������������������������������������������������������������������������������������� 49 Self-Assessment Questions����������������������������������������������������������� 107
Self-Assessment Questions������������������������������������������������������������� 53
Case Series: Orthostatic Hypotension
Recorded Webcast: Behavioral Approaches By Elizabeth Pogge, Pharm.D., MPH, FASCP, FAzPA, BCPS, BCGP
to Optimize Patient Engagement in a
Healthy Lifestyle Introduction ��������������������������������������������������������������������������������������112

By Lauren M. Hynicka, Pharm.D., BCPS; and Richard J. Rovelli, Pharm.D., Treatment of OH ������������������������������������������������������������������������������115
BCCP Consideration of Comorbid Conditions ��������������������������������������� 122

Recorded Webcast: Behavioral Approaches to Optimize Patient Clinical Practice Guidelines ����������������������������������������������������������� 124
Engagement in a Healthy Lifestyle ������������������������������������������������� 58
Conclusion ��������������������������������������������������������������������������������������� 126
References ����������������������������������������������������������������������������������������� 58
References ��������������������������������������������������������������������������������������� 126
Self-Assessment Questions������������������������������������������������������������� 60
Self-Assessment Questions����������������������������������������������������������� 129

Heart Failure with Preserved Ejection

Venous Thromboembolism: Primary
Fraction
Prevention
By Aimon C. Miranda, Pharm.D., BCPS; and Cyrille K. Cornelio, Pharm.D.,
By Allison E. Burnett, Pharm.D., CACP; and Kathryn E. Dane, Pharm.D.,
BCCP
BCPS
Introduction and Epidemiology ������������������������������������������������������� 65
Introduction to Venous Thromboembolism ������������������������������� 133
Pathophysiology ������������������������������������������������������������������������������� 66
Evolution of VTE Prevention Practices ��������������������������������������� 134
Clinical Evaluation and Diagnosis ������������������������������������������������� 67
VTE Risk Assessment Models ����������������������������������������������������� 135
Updates in Drug Therapy Management for HFpEF ��������������������� 69
Modalities of Thromboprophylaxis ��������������������������������������������� 140
Treatment of HFpEF ������������������������������������������������������������������������� 69
Clinical Evidence and Guideline Recommendations ��������������� 147

PSAP 2025 Book 1 • Cardiology xi Table of Contents

 Antithrombosis Stewardship Opportunities and Strategies����� 155 ECG Interpretation and Management
Conclusion ������������������������������������������������������������������������������������� 160 of QT Prolongation
References ������������������������������������������������������������������������������������� 160 By Zachary R. Noel, Pharm.D., Ph.D., BCCP; and Joseph S. Van Tuyl,
Pharm.D., BCCP
Self-Assessment Questions����������������������������������������������������������� 167
Introduction �������������������������������������������������������������������������������������203

Antithrombotic Therapy for Valvular Heart Basic Principles of the ECG �����������������������������������������������������������204
Disease Basic ECG Interpretation ���������������������������������������������������������������208
By Kelly M. Rudd, Pharm.D., FCCP, BCPS, CACP; and Amanda R. McFee Clinical Significance of the QT/QTc����������������������������������������������� 210
Winans, Pharm.D., BCPS, CACP
Measuring, Calculating, and Interpreting the QT/QTc ��������������� 212
Valvular Heart Disease ������������������������������������������������������������������� 171
Treatment of QT Prolongation and Patients at Risk ������������������� 215
Clinical Presentations �������������������������������������������������������������������� 172
Conclusion ��������������������������������������������������������������������������������������� 219
Surgical Valve Replacement ��������������������������������������������������������� 174
References ��������������������������������������������������������������������������������������� 221
Minimally Invasive Repair and Replacement ����������������������������� 181
Self-Assessment Questions�����������������������������������������������������������225
Chronic Care Considerations��������������������������������������������������������� 187
Anticoagulation Stewardship in Special Situations ������������������� 188
Conclusion ��������������������������������������������������������������������������������������� 194
References ��������������������������������������������������������������������������������������� 194
Self-Assessment Questions����������������������������������������������������������� 198

PSAP 2025 Book 1 • Cardiology xii Table of Contents

Hypertension
By Andrew Y. Hwang, Pharm.D., BCPS; and Christina H. Sherrill, Pharm.D., BCACP, BC-ADM

Reviewed by Rachel W. Khan, Pharm.D., BCPS; Samira Zantout, Pharm.D., BCPS, BCIDP, AAHIVP; and Jessica Reno, BSN,
Pharm.D., RN-BC, BCPS

LEARNING OBJECTIVES

1. Evaluate patient-specific factors related to the diagnosis of hypertension.

2. Analyze clinical practice guidelines and primary literature that affect current hypertension management strategies.
3. Develop an individualized hypertension treatment plan using a comprehensive approach.
4. Apply treatment strategies for patients with critical or difficult-to-treat hypertension.

INTRODUCTION
ABBREVIATIONS IN THIS CHAPTER
Hypertension Overview
ABPM Ambulatory blood pressure
monitoring Hypertension is defined as a sustained elevation in blood pressure
ACC American College of Cardiology above a certain threshold. The American Heart Association (AHA)
ACE Angiotensin-converting enzyme and American College of Cardiology (ACC) define this as systolic
AHA American Heart Association blood pressure (SBP) above 130 mm Hg and/or diastolic blood pres-
AOBP Automatic office blood pressure sure (DBP) above 80 mm Hg, whereas the European Society of Hyper-
ARB Angiotensin receptor blocker tension (ESH) uses the thresholds of SBP 140 mm Hg and DBP 90
ASCVD Atherosclerotic cardiovascular mm Hg (Mancia 2023; Whelton 2018). Appropriate hypertension treat-
disease ment is crucial, with one study showing mortality risk from stroke,
CCB Calcium channel blocker heart, or vascular disease doubling with increases in SBP of 20 mm
CKD Chronic kidney disease Hg and DBP of 10 mm Hg from a baseline of 115/75 mm Hg (Lewing-
DBP Diastolic blood pressure ton 2002), and another study showing a 53% increase in atheroscle-
eGFR Estimated glomerular filtration rate rotic cardiovascular disease (ASCVD) for every 10-mm Hg increase in
ESH European Society of Hypertension SBP above 90 mm Hg (Whelton 2020). Moreover, increased CVD risk
HBPM Home blood pressure monitoring related to elevated blood pressure spans patient populations from 30
HF Heart failure years to older than 80 years (Lewington 2002). Pharmacists play an
HFrEF Heart failure with reduced ejection important role in hypertension management, and studies have shown
fraction they can have a significant effect on helping to reduce both SBP and
ISH International Society of DBP (Dixon 2021; Wagner 2020).
Hypertension This chapter provides an update on the management of hyper-
MI Myocardial infarction tension with a focus on pharmacologic therapy. Nuances of treating
MRA Mineralocorticoid receptor specific populations and applying recent guidelines and primary liter-
antagonist
ature are also included.
NSAID Nonsteroidal anti-inflammatory
drug
Hypertension Epidemiology
PRA Plasma renin activity
Almost 120 million American adults (48.1%) have hypertension,
RAS Renin-angiotensin system
more than three-fourths of whom have uncontrolled hypertension
SBP Systolic blood pressure
(CDC 2023). Hypertension is more common in men than in women
T2D Type 2 diabetes
(51.0% vs 39.7%, respectively), and prevalence increases with age.
Table of other common abbreviations. Hypertension is more common in the non-Hispanic Black population
(57.1%) than in the Hispanic (43.7%) and non-Hispanic White (43.6%)

PSAP 2025 Book 1 • Cardiology 1 Hypertension

populations (Ostchega 2020). Costs related to hypertension the guidelines, they are not repeated in this chapter. However,
are around $131 billion per year in the United States (Kirkland clinicians should be reminded to allow the seated patient to
2018). rest for at least 5 minutes before blood pressure measurement
Globally, where hypertension is defined according to higher without talking, choose the appropriate cuff size, and assess
thresholds than in the United States, more than 1 billion peo- blood pressure on the basis of the average of at least two vis-
ple have hypertension (WHO 2023). Several risk factors con- its for hypertension diagnosis and at least two readings during
tribute to hypertension, including tobacco use, poor diet and a given visit for hypertension assessment and management
exercise habits, and comorbidities of diabetes, dyslipidemia, (Whelton 2018).
and obesity. Family history, advanced age, male sex, and low Manual or automatic office blood pressure (AOBP) can be
socioeconomic status have also been linked to hypertension used, though AOBP, when used properly, has been shown to
(Whelton 2018). A systematic analysis investigating 87 risk be more accurate. Automatic office blood pressure involves
factors across 204 countries and territories found that high the recording of multiple blood pressure readings with a fully
SBP led to more than 10 million avoidable deaths each year automated device, and proper use requires the patient to be
and was associated with more premature deaths than any alone in a quiet place. Potential benefits of AOBP include
other risk factor (GBD 2020). reducing measurement errors, automatically calculating aver-
ages from multiple readings, and allowing the clinician to
EVALUATION OF HYPERTENSION leave the room during measurement, which has been shown
to reduce the effects of white-coat hypertension (Roerecke
Blood Pressure Measurement
2019).
Office Measurement Technique
Proper technique for blood pressure measurement continues Out-of-Office Measurement
to be emphasized in the clinical guidelines (Mancia 2023; Whel- In addition to measurement of blood pressure in the clinical
ton 2018). Because specific steps are described extensively in setting, out-of-office measurements can be used to confirm
hypertension and monitor response to interventions. Out-of-
office measurements consist of home blood pressure mon-
itoring (HBPM) and ambulatory blood pressure monitoring
BASELINE KNOWLEDGE STATEMENTS (ABPM). Home blood pressure monitoring is performed by
individuals using their own blood pressure monitor, whereas
Readers of this chapter are presumed to be familiar
with the following: ABPM measures blood pressure every 15 minutes to 1 hour
using office-owned equipment. When choosing between
• Hypertension pathophysiology
these methods, it is important to consider the patient/care-
• Consequences of untreated or inadequately treated
giver preferences and needs. Although ABPM is usually pre-
hypertension
ferred to HBPM, it requires more office visits and may not be
• Appropriate blood pressure measurement
technique practical for all patients (Whelton 2018). Home blood pres-
sure monitoring requires choosing an appropriate device and
• Antihypertensive pharmacology
using it correctly. As telehealth has become more widespread,
Table of common laboratory reference values patient education on proper HBPM has become critical. Phar-
macists can help patients/caregivers choose a validated
device by using the “[Link]” website and provide
ADDITIONAL READINGS
counseling on use. Although some wrist monitors and smart-
The following free resources have additional back- watches are included on the website (American Medical Asso-
ground information on this topic: ciation 2023), upper arm monitors are preferred (American
• Whelton PK, Carey RM, Aronow WS, et al. ACC/ Medical Association 2024). Proper fit and validation in spe-
AHA/AAPA/ABC/ACPM/AGS/ APhA/ASH/ASPC/ cial populations (eg, older adults or pregnant patients) should
NMA/PCNA guideline for the prevention, detection,
also be considered (American Medical Association 2024).
evaluation, and management of high blood pres-
sure in adults. Hypertension. 2017;71. When in doubt, patients can bring their HBPM device to the
office to compare with office readings when making therapeu-
• Mancia G, Kreutz R, Brunstrom M, et al. 2023 ESH
tic decisions.
guidelines for the management of arterial hyperten-
sion. J Hypertens. 2023;41:1874-2071. Although time in therapeutic range (TTR) is not widely
• Munter P, Shimbo D, Carey RM, et al. Measurement used for blood pressure management, evidence supports the
of blood pressure in humans: a scientific statement association of TTR from ABPM with reduced CV risk (Fatani
from the American Heart Association. Hypertension. 2021). Specifically, the Japan Morning Surge-Home Blood
2019;73:e35-e66. Pressure (J-HOP) extended study, which defined TTR as an
SBP of 100 to 135 mm Hg, found that CV event risk decreased

PSAP 2025 Book 1 • Cardiology 2 Hypertension

by 4% and stroke risk decreased by 9% with a 10% increase in should be used periodically for patients with white-coat hyper-
TTR (Kario 2024). Therefore, when ABPM is used, TTR should tension to identify progression to sustained hypertension.
be evaluated and weighed in decision-making.
Of note, interpretations of clinic blood pressure readings, Secondary Hypertension
HBPM, and ABPM vary slightly. For example, HBPM of 135/85 In addition to screening for masked and white-coat hyperten-
mm Hg and daytime ABPM of 145/90 mm Hg correspond to sion, evaluation for and management of secondary causes
clinic values of 140/90 mm Hg and 160/100 mm Hg, respec- of hypertension can significantly improve or ameliorate ele-
tively. Nighttime ABPM runs an average of 20 mm Hg lower vated blood pressure as well as reduce CV risk. In particular, if
than clinic measurements for SBP (Whelton 2018). a patient presents with an abrupt elevation in blood pressure
(either without preexisting hypertension or with previously
Masked and White-Coat Hypertension
controlled hypertension) or hypertension onset at younger
Hypertension can be categorized as “sustained” (hyper- than 30 years, it is pertinent to screen for secondary causes
tension in-office and out-of-office settings), “masked” (out- of hypertension (Whelton 2018). Table 1 includes specific
of-office hypertension only), and “white coat” (in-office indications for screening for secondary causes of hyperten-
hypertension only). A person with in-office SBP consistently sion. Medical history, physical examination, and laboratory
120 to 129 mm Hg or DBP 75 to 79 mm Hg should be screened measurements can help identify specific causes of elevated
for masked hypertension using HBPM or ABPM. If daytime blood pressure in about 10% of adults with hypertension (Cal-
ABPM or HBPM exceeds 130/80 mm Hg, antihypertensive houn 2008). Obstructive sleep apnea, renovascular disease,
therapy should be initiated (Whelton 2018). Prevalence of and primary aldosteronism are among the most common
masked hypertension can be as high as 30% in normotensive causes of secondary hypertension that can be identified and
clinic populations (Gorostidi 2015). It is pertinent to assess for treated independently from blood pressure elevations (Whel-
masked hypertension and treat appropriately because CVD ton 2018). Of note, although appropriate treatment of reno-
and all-cause mortality risk in these individuals is twice that vascular disease and primary aldosteronism can improve
of persons without hypertension (Stergiou 2014). blood pressure control, evidence is lacking for the use of con-
It is reasonable to screen for white-coat hypertension using tinuous positive airway pressure for obstructive sleep apnea
HBPM or ABPM in individuals with in-office SBP 130 to 160 to improve blood pressure (Whelton 2018; Muxfeldt 2015).
mm Hg or DBP 80 to 100 mm Hg. In certain populations, the In the 2017 ACC/AHA guidelines, table 13 provides compre-
prevalence of white-coat hypertension can be up to 35%, and hensive information regarding screening for these as well as
identifying white-coat hypertension can reduce unnecessary other causes of secondary hypertension (Whelton 2018).
medications as well as associated costs and adverse effects Certain prescription and OTC medications, herbal and
(Piper 2015). Home blood pressure monitoring or ABPM dietary products, and illicit drugs can affect blood pressure.

Table 1. Screening for Common Causes of Secondary Hypertension

Potential Cause of Secondary

Specific Indication to Screen for Secondary Hypertension and Estimated
Hypertension Prevalencea Screening Components
Snoring; daytime sleepiness; resistant hypertension Obstructive sleep apnea, Weight; Epworth Sleepiness Scale
25%-50% score; nocturnal oximetry
Sudden or early (especially in women) hypertension Renovascular disease, 5%-34% Renal Duplex Doppler ultrasound;
onset; sudden worsening of hypertension; resistant abdominal CT
hypertension
Hypertension with presence of hypokalemia, muscle Primary aldosteronism, 8%-20% Plasma aldosterone/renin ratio;
cramps or weakness, adrenal mass, and/or obstructive arrhythmia (especially atrial
sleep apnea; resistant hypertension fibrillation)
Use of illicit drugs (cocaine, amphetamines), nicotine, Drug- or alcohol-induced, 2%-4% Tachycardia; sweating; acute
NSAIDs, caffeine, decongestants, sodium-containing abdominal pain (cocaine);
antacids, alcohol, oral contraceptives, cyclosporine or response after discontinuation
tacrolimus, neuropsychiatric agents, herbal products
(ephedra, ma huang), and others

CT = computed tomography; NSAID = nonsteroidal anti-inflammatory drug.

a
Prevalence may vary depending on patient-specific factors such as comorbidities and severity of hypertension.
Information from: Whelton 2018.

PSAP 2025 Book 1 • Cardiology 3 Hypertension

When possible, offending agents should be discontinued or shared decision-making with the patient. Risk-benefit of med-
their use reduced to avoid prescribing cascades. Short-term ication use should be weighed, and the best course of action
use of OTC decongestants or NSAIDs can cause transient may be to continue a medication known to increase hyperten-
increases in blood pressure. Chronic use of amphetamines, sion and treat the hypertension with additional non pharma-
certain antidepressants or atypical antipsychotics, systemic cotherapeutic and/or pharmacotherapeutic interventions.
corticosteroids, and oral contraceptives can be important
contributors to hypertension. In addition to discontinuing or CLINICAL GUIDELINE UPDATE
decreasing doses or durations of therapy, mitigation strate- The existence of numerous guidelines has led to differences
gies include forgoing systemic agents when possible, consid- in recommendations that reflect the diverse health care sys-
ering selective serotonin reuptake inhibitors in place of other tems, patient populations, and interpretations of the available
antidepressants, avoiding clozapine and olanzapine, and evidence. Table 2 provides a summary of the varying defini-
choosing low-dose or progestin-only contraceptives (Whelton tions in blood pressure classification and blood pressure tar-
2018). However, of importance, these adjustments are not gets within the most recently published guidelines by each
always possible, and care should be individualized using major national and international organization.

Table 2. Comparison of BP Classifications and Targets Between the Different Guidelines

Systolic Blood Diastolic Blood

BP Classification Pressure (mm Hg) Pressure (mm Hg) BP Targets
2017 ACC/AHA Normal < 120 < 80 < 130/80 mm Hg
Elevated 120-129 < 80
Stage 1 130-139 80-89 Assess risk-benefit among patients ≥ 65 yr
Stage 2 ≥ 140 ≥ 90 with high comorbidity burden
2023 ESH Optimal < 120 < 80 Primary objective:
Normal 120-129 80-84 < 140/80 mm Hg for most patients 18-79 yr
High-normal 130-139 85-89
Grade 1 140-159 90-99 If tolerated:
Grade 2 160-179 100-109 < 130/80 mm Hg recommended for
Grade 3 ≥ 180 ≥ 110 patients 18-64 yr
< 130/80 mm Hg considered for patients
Isolated systolic ≥ 140 < 90 65-79 yr
hypertension
SBP 140-150 mm Hg for patients ≥ 80 yr
Isolated diastolic < 140 ≥ 90 (SBP 130-139 mm Hg can be considered if
hypertension tolerated)

Avoid targeting < 120/70 mm Hg

2020 ISH Normal < 130 < 85 Essential:
High-normal BP 130-139 85-89 BP reduction by 20/10 mm Hg to
Grade 1 140-159 90-99 < 140/90 mm Hg
Grade 2 ≥ 160 ≥ 100
Optimal:
< 130/80 mm Hg (but > 120/70 mm Hg) for
patients < 65 yr
< 140/90 mm Hg for patients ≥ 65 yr
(if tolerated)
2022 NICE Stage 1 140-159 90-99 < 140/90 mm Hg for patients < 80 yr
Stage 2 160-179 100-119
Stage 3 ≥ 180 ≥ 120 < 150/90 mm Hg for patients ≥ 80 yr

Information from Mancia 2023; National Institute for Health and Care Excellence 2023; Unger 2020; Whelton 2018.
Abbreviations: ACC, American College of Cardiology; AHA, American Heart Association; BP, blood pressure; DBP, diastolic blood
pressure; ESH, European Society of Hypertension; ISH, International Society of Hypertension; NICE, National Institute for Health and
Care Excellence; SBP, systolic blood pressure.

PSAP 2025 Book 1 • Cardiology 4 Hypertension

2017 ACC/AHA Hypertension Guidelines pressure treatment targets on the basis of age, usually target-
The 2017 ACC/AHA guidelines lowered the diagnostic cut- ing a lenient blood pressure goal for patients 80 and older.
off of hypertension from 140/90 mm Hg to 130/80 mm
Hg, thereby shifting the classification of stage 1 and stage Other Hypertension Guidelines
2 hypertension to lower blood pressure thresholds. This The International Society of Hypertension (ISH) published
change expanded the number of individuals meeting the its own set of hypertension guidelines in 2020 (Unger 2020).
diagnostic criteria for hypertension, leading to an increased The guidelines were developed to be concise, easy to under-
prevalence of hypertension in the United States by about stand, and universally applicable, regardless of the resource
14% (Muntner 2018). The guidelines also lowered the recom- settings. To meet these goals, ISH opted to classify standards
mended blood pressure treatment target to 130/80 mm Hg for of care as “optimal” and “essential.” Optimal standards were
all patients with hypertension, which largely stemmed from based on the highest available evidence and usually aligned
randomized controlled trials that evaluated optimal blood with evidence-based recommendations outlined by other
pressure goals to reduce CV outcomes. The guidelines also hypertension guidelines at the time. For example, optimal
recommend initiation of antihypertensive medications in standards of care for blood pressure goals were consistent
patients with blood pressure of 130/80 mm Hg or greater with with the 2018 European Society of Cardiology/ESH guidelines
an elevated 10-year ASCVD risk. Other updates from the 2017 to target less than 130/80 mm Hg, but not less than 120/70
ACC/AHA guidelines include an emphasis on appropriate mm Hg, in patients younger than 65. Essential standards of
blood pressure measurement techniques and guidance on care were recommendations when optimal standards might
screening for white-coat hypertension and masked hyperten- not be feasibly implemented, such as in low-resource settings.
sion. Although the ACC/AHA guidelines pose the lowest blood The National Institute for Health and Care Excellence
pressure goal for the largest number of patients, they recom- (NICE) published guidelines on the diagnosis and man-
mend lifestyle intervention to reach that goal for patients at agement of hypertension in adults in 2019, which served to
low CV risk (less than 10%). provide updated guidance according to the new evidence pub-
lished after 2011 (National Institute for Health and Care Excel-
2023 ESH Hypertension Guidelines lence 2023). These updates included using an estimated CV
Compared with the 2018 ESH hypertension guidelines, the risk score to determine antihypertensive treatment and guid-
2023 iteration placed greater emphasis on using out-of-of- ance on patients with type 2 diabetes (T2D) (Boffa 2019).
fice blood pressure measurements in evaluating hyperten- Unlike other hypertension guidelines, the NICE guidelines did
sion, recommended an increase in potassium intake through not lower blood pressure targets to less than 130/80 mm Hg,
dietary modification to assist with lowering blood pressure, and instead added a relaxed goal of less than 150/90 mm Hg
and provided more specific guidance on the use of β-block- for patients older than 80. Minor updates were made in 2022
ers with selected comorbidities, such as chronic coronary and 2023, which included new recommendations for anti-
syndromes, heart failure (HF), and atrial fibrillation. In addi- hypertensive drug treatment and blood pressure targets for
tion, these guidelines were the first to address the concerns of patients with CVD and the management of postural hypoten-
hypertension management in the setting of COVID-19 (Man- sion (National Institute for Health and Care Excellence 2023).
cia 2023).
Both the 2023 ESH and the 2017 ACC/AHA guidelines rec- TREATMENT GOALS
ommend targeting a blood pressure of less than 130/80 mm The 2017 ACC/AHA guidelines tightened the blood pres-
Hg in patients at high CV risk, emphasize CV risk assessment sure goals to recommend targeting blood pressure less than
to guide initiation of antihypertensive medications, and sup- 130/80 mm Hg in most patients, including the older population
port the use of single-pill combination therapy to reduce pill without diabetes or kidney disease. The American Academy
burden. However, there are notable differences in a few key of Family Physicians and American College of Physicians dis-
recommendations. The 2023 ESH guidelines outline eight agreed with the stricter blood pressure targets and released
classifications of blood pressure, including five categories individual statements voicing their concerns (American Acad-
of hypertension. The guidelines provide further guidance for emy of Family Physicians 2024; Wilt 2018). Internationally,
managing isolated systolic hypertension, with an accompa- the 2023 ESH guidelines recommend a primary goal to tar-
nying caveat to avoid treating DBP to below 70 mm Hg. Initi- get blood pressure to less than 140/80 mm Hg because the
ation of antihypertensive treatment is recommended in most greatest protection from CVD arises at this range. If tolerated,
patients with blood pressure of 140/90 mm Hg or greater. a lower SBP target of 130 mm Hg is recommended, particu-
However, the presence of CVD is required if initiating drug larly among patients 18 to 64 years of age. In patients 65 and
therapy at blood pressure 130/80 mm Hg or greater, which is older, it is recommended to target more lenient SBP goals and
a higher risk threshold than in the 2017 ACC/AHA guidelines. only to lower SBP to stricter goals if treatment is well tolerated
The 2023 ESH guidelines also provide individualized blood (Mancia 2023). The variations in recommended blood pres-
sure targets during treatment across different hypertension

PSAP 2025 Book 1 • Cardiology 5 Hypertension

guidelines arise from inconsistencies within the available lit- events were similar between the groups (38.3% vs 37.1%; P
erature and differing interpretations of evidence. A review of = .25). However, the intensive-treatment group had a signifi-
the literature is provided in the text that follows. cantly higher incidence of hypotension, electrolyte abnormal-
ity, and acute kidney injury. Furthermore, intensive treatment
ACCORD-BP Trial was not associated with a statistically significant reduction
The Action to Control Cardiovascular Risk in Diabetes in the incidence of probable dementia, though mild cogni-
(ACCORD) study was a large randomized controlled trial inves- tive impairment was significantly reduced (Williamson 2019).
tigating whether intensive treatment of glycemia, lipids, and Although the results of the SPRINT study provided strong evi-
blood pressure would reduce CVD events in patients with T2D dence in support of an intensive blood pressure target, the
(Cushman 2010). The trial was conducted in 10,521 patients standardized blood pressure measurement and the exclusion
who were first randomized to receive intensive glycemic con- of patients with diabetes and stroke may limit the generaliz-
trol or standard glycemic control. The study participants were ability of the results in routine clinical practice.
then randomly assigned in a 2 × 2 factorial design into either
the lipid arm or the blood pressure arm. The blood pressure ACCORD-BP vs SPRINT
arm of ACCORD included 4733 patients who were randomized Both the ACCORD-BP and SPRINT studies investigated the
to receive intensive therapy targeting SBP less than 120 mm benefits of intensive antihypertensive treatment targeting an
Hg or standard of care (at the time) targeting SBP less than SBP less than 120 mm Hg. Despite achieving a similar mean
140 mm Hg. Blood pressure was measured by AOBP with a SBP, the studies came to disparate results. Several possible
clinician present (Kjeldsen 2016). After 1 year of therapy, the explanations have been proposed for why the ACCORD-BP
mean SBP was 119.3 mm Hg in the intensive group and 133.5 study did not find a statistically significant difference, whereas
mm Hg in the standard group. Despite these significant differ- the SPRINT study did. The sample size differences between
ences in blood pressure reduction between groups, the trial the trials indicate that the ACCORD-BP trial may have been
found no significant difference in the rate of the primary com- underpowered (Perkovic 2015). The 2 × 2 factorial design of
posite outcome of nonfatal myocardial infarction (MI), non- ACCORD-BP may have also attenuated the effect of intensive
fatal stroke, or death from CV causes. In addition, all-cause blood pressure treatment through interaction with the glyce-
mortality was similar between the 2 groups; however, signifi- mic treatment arms (Margolis 2014). Nonetheless, several
cantly lower annual rates of stroke were observed in the inten- studies pooling the ACCORD-BP and SPRINT trial populations
sive group. Serious adverse events, such as hypotension, have found that intensive blood pressure control may be ben-
bradycardia, and hyperkalemia, were significantly more com- eficial in groups at high CV risk, even in patients with diabetes
mon in the intensive group. at the highest CV risk (Brouwer 2018; Buckley 2017).

SPRINT Study STEP Trial

The Systolic Blood Pressure Intervention Trial (SPRINT) study The Strategy of Blood Pressure Intervention in the Elderly
was an open-label, randomized controlled trial conducted Hypertensive Patients (STEP) study is the latest trial since
across 102 clinical sites in the United States and Puerto Rico SPRINT to evaluate the efficacy and safety of intensive blood
(SPRINT Research Group 2021; Wright 2015). The trial was pressure treatment (Zhang 2021). The study was a multi-
conducted in 9361 patients without diabetes or prior stroke. center, randomized controlled trial of 8511 patients from
Enrolled patients were randomly assigned to receive intensive 42 clinical centers in China. Patients were eligible for the trial
treatment targeting an SBP less than 120 mm Hg or standard if they were 60 to 80 years of age with SBP between 140 and
treatment targeting an SBP less than 140 mm Hg. Standard- 190 mm Hg or taking antihypertensive medications. History
ized blood pressure measurement was implemented in which of ischemic or hemorrhagic stroke was an exclusion criterion.
participants’ blood pressure was measured using an AOBP Eligible patients were randomly assigned to receive intensive
device in a quiet room, unobserved by a clinician (Kjeldsen treatment targeting SBP between 110 and 129 mm Hg or stan-
2016). The trial was terminated early because the primary dard treatment targeting SBP between 130 and 149 mm Hg.
analysis results exceeded the monitoring boundary at 2 con- Antihypertensive medications used in the trial included olme-
secutive time points. The median follow-up was 3.26 years. sartan, amlodipine, and hydrochlorothiazide. The median fol-
At the end of the study, the mean SBP was 121.5 mm Hg in low-up was 3.34 years. After 1 year of follow-up, the mean SBP
the intensive-treatment group and 134.6 mm Hg in the stan- was 127.5 mm Hg in the intensive-treatment group and 135.3
dard-treatment group. Significant reduction in the primary mm Hg in the standard-treatment group, which remained con-
composite outcome of MI, acute coronary syndrome, stroke, sistent throughout the study at 126.7 mm Hg and 135.9 mm
acute decompensated HF, or death from CV causes occurred Hg, respectively. The incidence of the primary composite out-
in the intensive-treatment group compared with the stan- come of stroke, acute coronary syndrome, acute decompen-
dard-treatment group (5.2% vs 6.8%; hazard ratio [HR] 0.75; sated HF, coronary revascularization, atrial fibrillation, or CV
95% CI, 0.64-0.89; P < .001). Rates of overall serious adverse death was significantly lower in the intensive-treatment group

PSAP 2025 Book 1 • Cardiology 6 Hypertension

than in the standard-treatment group (3.5% vs 4.6%; HR 0.74; specifically mention the use of lower doses of a combination
95% CI, 0.60-0.92; P = .007), which appeared to be driven of antihypertensives rather than titrating to maximum doses
by reduction in stroke, acute coronary syndrome, and acute before adding on additional therapy as a strategy to mitigate
decompensated HF. Serious adverse events, such as syncope the adverse effects seen at high doses of antihypertensives
and fracture, did not significantly differ between the groups. (Mancia 2023).
However, hypotension occurred at a higher incidence in the
Assessment of CV Risk and Comorbidities
intensive-treatment group than in the standard treatment
group (3.4% vs 2.6%; P = .03). Although various methods to assess CV risk exist, there is no
The results of the STEP trial provide additional confirma- universal calculator that can be applied to all patients with
tion of the benefits of targeting a lower blood pressure goal hypertension. Although the 2017 ACC/AHA guidelines recom-
among older adults with hypertension. The trial highlights the mend the ACC/AHA Pooled Cohort Equations, which estimate
additional CV protection afforded at the lower blood pressure 10-year ASCVD risk, these equations have been validated spe-
target, without increasing the risk of serious adverse events. cifically in Americans 40 to 79 years of age not treated with
The results are similar to the prespecified subgroup analy- statin therapy. As such, caution should be used when inter-
sis of adults 75 and older from the SPRINT study. The inci- preting these results for persons not fitting this description.
dence rate of the primary composite outcome was 2.59% per Lifestyle Interventions
year among the 1317 participants assigned to intensive treat-
Nonpharmacologic interventions can help prevent and man-
ment compared with 3.85% per year among the 1319 partici-
age hypertension as well as reduce CV risk (Prabhakaran
pants assigned to standard treatment, for an HR of 0.67 (95%
2018). Specifically, weight loss and increased physical activ-
CI, 0.49-0.91) (Williamson 2016). In addition, like the SPRINT
ity, adhering to a heart-healthy diet (eg, Dietary Approaches
study, the results of the STEP trial may not be generalizable to
to Stop Hypertension [DASH] diet), limiting alcohol consump-
patient populations not included in the trial, such as patients
tion, restricting sodium, and potassium supplementation have
with a history of stroke.
been shown effective in preventing and treating hypertension
(Whelton 2018).
HYPERTENSION MANAGEMENT Individuals at risk of, or diagnosed with, hypertension
should aim for a goal of achieving a healthy body weight and
Principles Guiding Initial Therapy
composition with body mass index of 18.5 to less than 25
As noted earlier, there are several modifiable and nonmodi-
kg/m2 with sufficient muscle mass, with a 1-mm Hg decrease in
fiable risk factors for hypertension, as well as secondary
SBP expected for every 10-kg decrease in body weight (Whel-
causes of hypertension. Management of hypertension should
ton 2018). Aerobic exercise for 90 to 150 minutes per week
include associated screenings and interventions, as appropri-
is recommended, together with resistance exercises thrice
ate, to guide initial therapy and achieve optimal health care
weekly. Alcohol should be limited to no more than 2 drinks
goals.
per day for men or 1 drink per day for women, and alcohol use
Interventions for hypertension management should
should be further restricted or avoided in certain populations
include nonpharmacologic therapy and pharmacologic ther-
(eg, older adults with high fall risk, persons with interacting
apy, and emphasis should be placed on CV risk reduction.
medications, pregnant women). The goal for sodium restric-
Pharmacologic interventions for hypertension management
tion is to consume less than 1500 mg daily or at least 1000 mg
should be based on blood pressure target in conjunction with
less per day compared with baseline, and potassium should
CV risk assessment. Specifically, for a patient with stage 1
be consumed at 3500 to 5000 mg daily (Whelton 2018). Fur-
hypertension (ie, SBP 130 mm Hg or greater and/or DBP 80
thermore, the Salt Substitute and Stroke Study (SSaSS) found
mm Hg or greater), evidence is stronger for the use of pharma-
that in a population with increased CV risk and high salt and
cologic interventions for those with higher CV risk (ie, history
low potassium intake at baseline, individuals using a salt sub-
of coronary heart disease, HF, or stroke; 10-year ASCVD risk
stitute with 25% potassium chloride had a lower risk of stroke,
of 10% or higher), and agents with known CV benefit are pre-
death, and CV events than those using 100% sodium chloride
ferred (Whelton 2018).
(Neal 2021). Although potassium supplements can be used,
Furthermore, the number of medications to start as ini-
dietary intake is usually preferred because it is consistent
tial therapy varies depending on the extent of blood pressure
with a heart-healthy diet (Mancia 2023; Poorolajal 2017).
elevation, where patients presenting with stage 2 hyperten-
sion (ie, SBP 140 mm Hg or greater and/or DBP 90 mm Hg Plasma Renin Activity–Guided Therapy
or greater) may be initiated on combination antihypertensive Use of plasma renin activity (PRA) to guide therapy for hyper-
therapy. Of note, drugs from different classes should be used tension management consists of preferentially choosing
when combination therapy is warranted, and multiple medi- pharmacologic agents according to measured PRA concen-
cations acting on the renin-angiotensin system (RAS) should trations. For higher PRA concentrations (vasoconstriction-
not be used concurrently (Whelton 2018). The ESH guidelines mediated hypertension), agents that act directly on the RAS or

PSAP 2025 Book 1 • Cardiology 7 Hypertension

β-blockers that decrease renin release can be used, whereas include ACE inhibitors, ARBs, thiazide diuretics, and CCBs
diuretics and calcium channel blockers (CCBs) are favored in (Fretheim 2012). These first-line agents are described in the
those with lower PRA concentrations (ie, volume-mediated text that follows, as well as Table 3. Other classes, which are
hypertension). Although some studies have shown a benefit discussed later, lack similar evidence and/or pose additional
in this approach to therapy, specific thresholds used to define safety risks.
high versus low PRA concentrations have not been consis- An overview of antihypertensive classes is provided ini-
tent, and evidence is conflicting based on ethnicity. Further- tially, and individualization of therapy on the basis of comor-
more, the usefulness of PRA-guided therapy may be limited bidities and other patient-specific factors is discussed in the
by cost and ease of measurement. following.
A recent study in India showed a pre/post decrease in SBP
Renin-Angiotensin System
up to 19.5 mm Hg (in group taking three antihypertensives at
baseline) and reduction in the number of antihypertensives Medications in the RAS that are first-line agents for hyperten-
(26% taking 1 drug at baseline vs 76% after PRA-guided ther- sion management include ACE inhibitors (eg, enalapril, lisino-
apy) when participants’ PRA concentration was measured pril, ramipril) and ARBs (eg, losartan, olmesartan, valsartan).
after a 2-week antihypertensive washout (Murty 2022). Anti- Angiotensin-converting enzyme inhibitors and ARBs have
hypertensives were then reinitiated according to PRA concen- been available since the 1980s and 1990s, respectively, and
tration. Therapy for those with a PRA less than 0.51 ng/mL/h have been extensively studied. Many important benefits have
consisted of diuretics and/or CCBs, whereas therapy for those been seen in clinical trials, including reduction in the risk of MI,
with a PRA greater than 2.64 ng/mL/h included angioten- stroke, and CV death (Savarese 2013). These agents decrease
sin-converting enzyme (ACE) inhibitors, angiotensin receptor angiotensin II activity: ACE inhibitors prevent the conversion
blockers (ARBs), and/or β-blockers. Of note, measurement of of angiotensin I to angiotensin II, and ARBs block angiotensin
PRA required participants to be in the fasting state and to lie II from binding to receptors. This prevents vasoconstriction
in the supine position for 15 minutes before the 2-mL blood and decreases glomerular filtration pressure, thereby reducing
collection. blood pressure. Because of their overlapping mechanisms of
Another study showed that PRA correlated to blood pres- action, ACE inhibitors and ARBs should not be used in com-
sure response in the European American population, but not bination with one another or with a direct renin inhibitor (ie,
the African American population (Mehanna 2019). This study aliskiren).
used PRA concentrations of less than 0.65 ng/mL/h, which Because of their mechanism of action, ACE inhibitors and
favored chlorthalidone, versus 0.65 ng/mL/h or greater, which ARBs can cause hyperkalemia. With the increase in potassium
correlated to greater improvements with metoprolol. Other tri- that can occur with ACE inhibitors and ARBs, combining them
als have shown PRA-guided therapy to be cost-effective for with a thiazide diuretic can help normalize potassium concen-
certain populations (younger, higher CV risk) and better than trations. In addition, because of their mechanism of action,
care provided by a clinical hypertension specialist, whereas a there is an expected hemodynamic effect on the kidney and
study of the older adult population showed no benefit over a vasculature when ACE inhibitors and ARBs are initiated and
fixed-dose therapy model (Smith 2013; Weintraub 2012; Egan doses increased. When other etiologies of prerenal acute kid-
2009). ney injury are present, acute kidney injury may ensue; how-
According to this evidence, older adults and African Amer- ever, ACE inhibitors and ARBs are otherwise renoprotective
icans seem less likely to benefit from PRA-guided therapy, and should be continued if the increase in serum creatinine is
whereas PRA-guided therapy can be considered in individu- less than 30% from baseline (Bakris 2000).
als with untreated hypertension who are of Indian or European A dry cough, which is more common in women and peo-
American descent, younger age, higher CV risk, and/or have ple of Asian descent, can occur in up to 34% of people tak-
limited access to a hypertension specialist. Of importance, ing an ACE inhibitor (Tseng 2010). If a patient experiences a
PRA should be measured in the absence of antihyperten- dry cough with an ACE inhibitor, an ARB can be used instead.
sive use. If PRA-guided therapy is desired for a patient cur- If ACE inhibitor–associated angioedema occurs, an ARB can
rently using antihypertensives, caution should be exercised be tried at least 6 weeks after ACE inhibitor discontinuation.
when discontinuing therapy, and safety protocols should be Of note, angioedema is more common in African American
employed (Beeftink 2017). patients (Kostis 2018). Both ACE inhibitors and ARBs should
be avoided in pregnancy.
First-line Pharmacotherapy The direct renin inhibitor, aliskiren, also functions on the
Use of pharmacotherapy for hypertension is based not only RAS and is contraindicated in pregnancy. Unlike ACE inhibi-
on blood pressure level, but also CV risk. This is because of tors and ARBs, however, aliskiren lacks outcomes data, which
evidence that certain antihypertensives decrease the risk limits its use.
of CV and cerebrovascular events as well as death (Ettehad
2016). Antihypertensive classes that carry this added benefit

PSAP 2025 Book 1 • Cardiology 8 Hypertension

 Table 3. First-line Antihypertensives

Adverse
Class Examples Administration Effects Contraindications Monitoring Pearls
ACE inhibitors Enalapril, lisinopril, Once or twice Hyperkalemia, Pregnancy, K, SCr Hold if SCr
ramipril daily cough, previous increases
angioedema angioedema, > 30% from
K > 5.5 mEq/L, baseline
bilateral renal
artery stenosis
ARBs Losartan, Once or twice Hyperkalemia, Pregnancy, K > 5.5 K, SCr Hold if SCr
olmesartan, daily angioedema mEq/L, bilateral increases
valsartan renal artery > 30% from
stenosis baseline; can
use in patients
who are ACE
inhibitor
intolerant (if
ACE inhibitor–
induced
angioedema,
wait 6 wk to
initiate ARB)
Thiazide Hydrochlorothiazide, Once daily Hyponatremia, Sulfonamide K, Na, SCr, Chlorthalidone
diuretics chlorthalidone, hypokalemia allergy calcium, preferred; take
indapamide uric acid in the morning
because of
diuretic effect
Dihydropyridine Amlodipine, Once or twice Pedal edema Avoid in HFrEF
CCBs felodipine, daily (can use
nifedipine amlodipine
and felodipine
if necessary);
pedal edema
is dose related
and more
common in
females
Non- Diltiazem, verapamil Once, twice, or Constipation, Heart block, HF Pulse rate Avoid in HFrEF;
dihydropyridine thrice daily bradycardia do not use with
CCBs β-blockers;
watch for DDIs
by CYP3A4 or
P-glycoprotein

Information from Mancia 2023; Whelton 2018.

Abbreviations: ACE, angiotensin-converting enzyme; ARB, angiotensin receptor blocker; CCB, calcium channel blocker; DDI, drug-
drug interaction; HF, heart failure; HFrEF, heart failure with reduced ejection fraction; K, potassium; Na, sodium; SCr, serum
creatinine.

Thiazide Diuretics convoluted tubule, which causes excretion of sodium and

Thiazide diuretics include thiazide-type agents (eg, hydro- water. A portion of sodium is reabsorbed in the collecting duct
chlorothiazide) and thiazide-like agents (eg, chlorthalidone, and exchanged with potassium, which also causes excretion
indapamide). Thiazide diuretics exhibit their diuretic effect of potassium. In addition to diuretic effects, thiazide diuret-
by blocking the sodium-chloride cotransporter in the distal ics are thought to decrease vascular resistance when used

PSAP 2025 Book 1 • Cardiology 9 Hypertension

long term, which promotes sustained blood pressure reduc- (Thomopoulos 2015). However, amlodipine and felodipine are
tion (Ernst 2022). preferred if a CCB is needed. Concomitant use of non-dihydro-
Because of their mechanism of action, thiazide diuret- pyridine CCBs and β-blockers should be avoided because of
ics can cause hyponatremia and hypokalemia. Thiazide-re- bradycardia and heart block risk, and CYP3A4 drug interac-
lated hypokalemia is also associated with hyperglycemia, but tions should be assessed.
proper treatment of hypokalemia can diminish this effect. In
addition, thiazide diuretics compete with uric acid for renal Second-line Pharmacotherapy
tubular secretion and can thus cause hyperuricemia; how- In most patients with hypertension, the initial choice of anti-
ever, they can be used with comorbid gout if properly treated hypertensive drug regimens should consist of agents from
with a urate-lowering medication (eg, allopurinol) (Sica 2011). the following major classes: ACE inhibitors/ARBs, CCBs, and
Therefore, electrolytes and uric acid should be monitored in thiazide/thiazide-like diuretics. Combination therapy is com-
patients using thiazide diuretics. mon in most patients with hypertension, and regimens should
Because of its long half-life and the reduction in CVD seen prioritize combinations from these drug classes. If blood
in clinical trials, chlorthalidone is the preferred agent of this pressure reduction with one agent from a particular class is
class (Whelton 2018; Olde Engberink 2015). However, hydro- suboptimal, clinicians should consider changing or adding on
chlorothiazide is available in combination with other antihy- therapy from another drug class. With adequate adherence,
pertensives in a single pill and is widely used. The Diuretic most patients can achieve optimal blood pressure control
Comparison Project was a real-world, multicenter, open-label, through a combination of two or three agents from these first-
head-to-head study comparing continuation of hydrochloro- line drug classes.
thiazide with change to chlorthalidone in 13,523 older adults However, in certain situations, use of second-line agents
with hypertension being treated with hydrochlorothiazide ther- may be warranted. Some patients may present with intoler-
apy (Ishani 2022). Although office blood pressure, major CV ances or contraindications to one or more of the four first-line
events, and non–cancer-related deaths were similar between drug classes. In addition, other patients may have suboptimal
the groups over a median follow-up of 2.4 years, there was blood pressure control despite the appropriate combination
benefit in the chlorthalidone group in subjects with a previous use of the first-line drug classes. In these patient populations,
MI or stroke. Of note, the median doses of hydrochlorothia- second-line therapy, either as alternative agents or add-on
zide and chlorthalidone were 23 mg and 12.3 mg, respectively, therapy, may be appropriate to help attain blood pressure con-
which is lower than those in which CV benefit has been shown trol. Finally, these second-line drug classes often have dual
(ALLHAT 2002). Hypokalemia was more common in the chlor- indications, making them particularly beneficial for patients
thalidone group. with specific comorbidities (Table 4).
Because the earlier study does not confirm the superior-
ity of chlorthalidone, hydrochlorothiazide is still reasonable ß-Blockers
in patients who require combination antihypertensive therapy Several meta-analyses of studies comparing different classes
and wish to reduce their pill burden by choosing a combina- of antihypertensive medications have found that β-blockers
tion product that includes hydrochlorothiazide. may be associated with less protection against stroke than
the other first-line classes (Thomopoulos 2020; Wei 2020).
Calcium Channel Blockers Current US guidelines recommend that β-blockers only be
Calcium channel blockers can be categorized as dihydropyri- used as part of initial therapy if there is a compelling indica-
dine (eg, amlodipine, felodipine, nifedipine) or non-dihydropy- tion, such as HF or atrial fibrillation.
ridine (eg, diltiazem, verapamil). Dihydropyridine CCBs cause Third-generation β-blockers such as nebivolol and carve-
calcium-mediated coronary and peripheral arterial vasodi- dilol have garnered attention for their additional direct vaso-
lation. Because of peripheral vasodilation, dihydropyridine dilatory properties, making them particularly interesting in
CCBs are associated with pedal edema, flushing, headache, hypertension management. This added vasodilatory effect
and tachycardia/palpitations. However, non-dihydropyridine is believed to contribute to further reduction in blood pres-
CCBs decrease blood pressure through negative inotropic sure, potentially positioning these β-blockers as the preferred
and chronotropic effects. Bradycardia is a common adverse choice in patients with hypertension. However, despite these
effect of non-dihydropyridine CCBs because of the negative theoretical advantages, no clinical trial data show superior CV
chronotropic effects, and constipation can occur with high outcomes with third-generation β-blockers compared with
doses of verapamil. other β-blockers. Although large-scale observational studies
Ideally, all CCBs would be avoided for HF with reduced ejec- have yielded inconsistent findings, some research suggests
tion fraction (HFrEF) because of negative inotropic effects third-generation β-blockers have fewer side effects than other
and potential to cause reflex tachycardia and fluid retention, β-blockers (Huck 2022; Chan You 2021).
as well as evidence that they are inferior in preventing HF

PSAP 2025 Book 1 • Cardiology 10 Hypertension

 Table 4. Second-line Antihypertensives

Class Examples Specific Populations Precautions

β-Blockers Atenolol, metoprolol HFrEF, CCD, atrial fibrillation, Bradycardia
succinate, carvedilol migraine prophylaxis
Avoid abrupt discontinuation
because of risk of withdrawal
syndrome
MRAs Spironolactone, HFrEF, CKD Hyperkalemia, sex hormone–related
eplerenone side effects (spironolactone)

Avoid in advanced kidney disease

α-Blockers Doxazosin, prazosin BPH, ED Orthostatic hypotension
Central α-agonists and Clonidine, methyldopa Anxiety disorders (clonidine), Anticholinergic effects
centrally acting drugs pregnancy (methyldopa)
Avoid abrupt discontinuation
because of risk of rebound
hypertension
Vasodilators Hydralazine, minoxidil, HFrEF (isosorbide dinitrate and Reflex tachycardia and fluid retention
nitrates hydralazine combination) (often paired with β-blocker and
diuretic to mitigate effects)

Abbreviations: BPH, benign prostatic hyperplasia; CCD, chronic coronary disease; CKD, chronic kidney disease; ED, erectile dysfunc-
tion; HFrEF, heart failure with reduced ejection fraction; MRA, mineralocorticoid receptor antagonist.

Mineralocorticoid Receptor Antagonists Considerations in Comorbid Conditions

Although outcomes data regarding the use of mineralocor- Comorbidities, such as diabetes and CKD, often accompany
ticoid receptor antagonists (MRAs) as first-line therapy for hypertension, compounding the complexity of its manage-
hypertension are limited, recent evidence underscores their ment and amplifying the risk of adverse health outcomes. The
effectiveness as adjunctive agents in cases of resistant presence of comorbid conditions can complicate treatment
hypertension (Chen 2020). In the Prevention and Treatment of strategies, given that certain antihypertensives may interact
Hypertension with Algorithm-based Therapy 2 (PATHWAY-2) with concurrent therapies or exacerbate underlying condi-
trial, spironolactone was the most effective at lowering blood tions. Therefore, a comprehensive approach to hypertension
pressure when used as an add-on agent for the treatment of is necessary to control blood pressure appropriately and mit-
resistant hypertension (Williams 2015). Moreover, MRAs are igate the overall CV risk. Most contemporary hypertension
considered a cornerstone treatment in HF management. Fur- guidelines provide specific recommendations for managing
thermore, recent studies have shown the renal benefits of hypertension in the setting of certain comorbid conditions.
MRAs in patients with chronic kidney disease (CKD) (Currie Although management of these conditions is beyond this
2016). Among the steroidal MRAs available, spironolactone is chapter’s scope, the text that follows outlines key consider-
notable for its potential potency, although with an increased ations for managing hypertension in the presence of selected
risk of sex hormone–related side effects. Conversely, eplere- comorbidities.
none offers a similar pharmacologic profile with a potentially
Type 2 Diabetes
lower incidence of adverse effects. A novel nonsteroidal MRA,
finerenone, has shown promising antihypertensive effects, Both the 2017 ACC/AHA and the 2023 ESH hypertension
though it is not yet FDA approved for hypertension manage- guidelines recommend targeting a blood pressure goal of less
ment in the United States. Of note, clinical trials have shown than 130/80 mm Hg in patients with hypertension and T2D
that finerenone elicits a reduction in SBP of about 2.7 mm Hg (Mancia 2023; Whelton 2018). In the past, this stricter blood
compared with placebo in patients with diabetic kidney dis- pressure goal conflicted with recommendations from the
ease, suggesting its potential role in hypertension (Ruilope American Diabetes Association (ADA), which previously rec-
2022). ommended targeting blood pressure to less than 140/90 mm
Hg; however, the ADA guidelines have since aligned their rec-
ommendations to support targeting this lower blood pressure

PSAP 2025 Book 1 • Cardiology 11 Hypertension

threshold (American Diabetes Association 2024). Although Previous literature has shown the renoprotective bene-
the ACCORD trial failed to show significant reductions in the fits of ACE inhibitors and ARBs in patients with CKD, par-
primary outcome, it found a significant reduction in stroke ticularly in the presence of moderate to severe albuminuria
when patients were targeted to the lower blood pressure goal (Strippoli 2004). The 2017 ACC/AHA, 2021 KDIGO, and 2023
(Cushman 2010). In addition, recent evidence from meta-anal- ESH hypertension guidelines recommend the initiation of an
yses have shown a small added protection against stroke and ACE inhibitor or ARB as first-line therapy in patients with ele-
coronary heart disease among trials that achieved SBP to less vated blood pressure and CKD with albuminuria, particularly
than 130 mm Hg compared with higher values in patients with in patients with a 300 mg/g urine albumin-to-creatinine ratio
hypertension and T2D (Thomopoulos 2017; Emdin 2015). or greater. Suggested combination therapy should consist of
The 2017 ACC/AHA and 2023 ESH hypertension guide- an ACE inhibitor or ARB plus a CCB or diuretic. Thiazide diuret-
lines recommend initiating any of the first-line antihyperten- ics should be the initial choice if the eGFR is above 30 mL/
sive classes in patients with elevated blood pressure and T2D min/1.73 m2. If the eGFR decreases below this threshold (ie,
because all 4 classes have been shown effective in this pop- CKD stages 4 and 5), clinicians should consider transitioning
ulation. Often, combination therapy is needed to effectively to a loop diuretic because this may be more effective at lower
control blood pressure, and preference is made to select ACE eGFRs, particularly if the elevation in blood pressure is vol-
inhibitors or ARBs as one of the combination agents to provide ume related. However, newer evidence suggests that chlor-
renoprotection against diabetic kidney disease, particularly thalidone is effective at lowering blood pressure in patients
among patients with albuminuria. Recently, sodium-glucose with CKD stage 4 (Agarwal 2021). In addition, growing evi-
cotransporter-2 (SGLT2) inhibitors have gained interest in the dence with SGLT2 inhibitors and finerenone, a nonsteroidal
management of T2D for their CV benefits. Although SGLT2 MRA, indicates that these newer agents are effective at low-
inhibitors are not indicated for managing hypertension, they ering blood pressure and slowing CKD progression in specific
can produce a modest blood pressure–lowering effect rang- populations. The SGLT2 inhibitors can be used in patients
ing from 3 to 9 mm Hg, which can help some patients achieve with eGFR 20 mL/min/1.73 m2 or greater to manage diabetic
blood pressure control (Kario 2019). Nonetheless, close mon- or non-diabetic CKD. Finerenone is indicated in patients with
itoring of blood pressure is required during initiation or titra- diabetic kidney disease and albuminuria if the eGFR is 25 mL/
tion of SGLT2 inhibitors to avoid hypotension. min/1.73 m2 or greater and serum potassium is less than 5.0
mEq/L.
Chronic Kidney Disease
In 2021, Kidney Disease: Improving Global Outcomes (KDIGO) Heart Failure
released updated guidance on the management of blood Elevated blood pressure can contribute to the worsening of
pressure in patients with CKD (Cheung 2021). One of the key HF. Therefore, management of hypertension can help prevent
updates from the 2021 guideline was the lowering of the SBP an exacerbation of underlying HF. Many of the antihyperten-
target to less than 120 mm Hg, with the caveat that standard- sive agents are recommended as part of the guideline-directed
ized office blood pressure measurements should be used to medical therapy for treating HF, which include ACE inhibitors,
attain accurate blood pressure readings. Of note, the KDIGO ARBs, β-blockers (specifically, bisoprolol, carvedilol, and
guidelines acknowledge this recommendation may not apply metoprolol succinate), and MRAs (Heidenreich 2022). These
to certain subgroups, such as those with CKD stages 4 and medications not only lower blood pressure but also provide CV
5 (estimated glomerular filtration rate [eGFR] less than 30 benefits in HF. Diuretics are often recommended in patients
mL/min/1.73 m2), diabetes, and kidney transplants. This with HF to assist with fluid management and reduce conges-
lower threshold was based on the results of the subgroup of tion, with loop diuretics preferred for severe fluid retention
patients with CKD in the SPRINT trial, which showed that tar- or advanced CKD. The 2022 AHA/ACC/Heart Failure Society
geting an intensive SBP level had a relative reduction in the of America HF guidelines also recommend an angiotensin
rates of major CV events and all-cause mortality by 19% com- receptor-neprilysin inhibitor and SGLT2 inhibitor (Heidenreich
pared with a goal of less than 140 mm Hg (Cheung 2017). This 2022). Although angiotensin receptor-neprilysin inhibitor and
recommendation differs from the 2017 ACC/AHA and 2023 SGLT2 inhibitors are not currently indicated for the treatment
ESH hypertension guidelines, both of which advocate a tar- of hypertension, they have the added benefit of lowering blood
get of less than 130 mm Hg (Mancia 2023; Whelton 2018). pressure. Although dihydropyridine CCBs should generally
The 2017 ACC/AHA guidelines acknowledge that the rationale be avoided, amlodipine and felodipine can be safely used in
behind the more conservative goal stems from the potential patients with HF. Non-dihydropyridine CCBs should be avoided
impracticality of standardized blood pressure measurement because they can increase the risk of HF exacerbation. Goal
in all health care facilities; whereas the 2023 ESH guidelines blood pressure should be targeted to less than 130/80 mm Hg,
suggest that supporting data for adopting a lower SBP target though careful attention must also be paid to titrating medi-
of less than 120 mm Hg are limited. cations to avoid hypotension and worsening HF symptoms
(Whelton 2018).

PSAP 2025 Book 1 • Cardiology 12 Hypertension

Chronic Coronary Disease agents can vary in severity, ranging from nonspecific symp-
Blood pressure control is an important aspect in the manage- toms like dizziness to those specific to certain classes, such
ment of chronic coronary disease, which includes coronary as angioedema associated with ACE inhibitors.
artery disease, ischemic heart disease, and chronic angina,
to mitigate the risk of adverse CV events and progression of Electrolyte Abnormalities
atherosclerosis (Virani 2023). Data support targeting a blood Hyperkalemia is a common side effect of drugs that inhibit
pressure goal of less than 130/80 mm Hg, which has been the RAS, particularly in patients with CKD (Hundemer 2021;
shown to significantly reduce CV complications and mor- Weinberg 2009). Routine monitoring of serum potassium con-
tality (Bundy 2017). Guideline-directed medical therapy rec- centrations is imperative to identify and prevent hyperkale-
ommends the use of β-blockers, ACE inhibitors, and ARBs mia during treatment, with follow-up potassium and kidney
as initial therapy, given the abundance of data surrounding function laboratory tests within 2 to 4 weeks of initiation or
their use in this patient population (Virani 2023). Specifically, dose titration. Once the patient is being treated with a stable
β-blockers have antianginal properties, which may be helpful dose of the RAS inhibitor, follow-up laboratory values can be
in patients with a recent MI and persistent anginal symptoms. measured annually. Dose reduction or discontinuation of the
The β-blockers preferred by the guidelines include carvedilol, offending agent is an effective strategy to manage hyperka-
metoprolol tartrate, metoprolol succinate, bisoprolol, nado- lemia, albeit at the risk of blood pressure becoming uncon-
lol, propranolol, and timolol (Virani 2023). If additional blood trolled. Initiation of potassium-depleting diuretics, such as
pressure lowering is required, clinicians can consider adding thiazide and loop diuretics, can help mitigate the increase
other antihypertensives, such as thiazide diuretics, dihydropy- in blood pressure while also lowering potassium concentra-
ridine CCBs, and MRAs. Dihydropyridine CCBs can be partic- tions. Dietary modification to reduce potassium intake to less
ularly effective when used as add-on therapy to β-blockers in than 3 g per day can also be helpful to manage hyperkalemia,
patients with CCD and angina because these agents also have particularly in patients with CKD (Cheung 2021). However, this
antianginal properties (Whelton 2018). should be done cautiously because it could lead to a reduc-
tion in dietary fiber, antioxidants, and alkali intake. Other, less
Stroke common options include initiating drugs that increase fecal
Blood pressure management in patients with previous stroke potassium excretion, such as sodium polystyrene sulfonate,
or transient ischemic attack is crucial because hypertension patiromer, and sodium zirconium cyclosilicate (Hundemer
is a well-established risk factor for stroke recurrence and com- 2021). Of note, a small retrospective study has shown that
plications (Kleindorfer 2021). Historically, concerns existed sodium zirconium cyclosilicate may allow patients with CKD
regarding the potential negative outcomes of lowering blood and hyperkalemia to continue with a RAS inhibitor (Kimura
pressure in patients with prior stroke. However, recent evi- 2024).
dence indicates that lowering SBP to less than 130 mm Hg Thiazide/thiazide-like diuretics and loop diuretics can
can significantly reduce the risk of recurrent stroke (Katsanos cause hypokalemia, hypomagnesemia, and hypophospha-
2017). Therefore, the 2021 AHA/American Stroke Association temia. These abnormalities often occur within the first 2 to 3
guideline recommends targeting a blood pressure goal of less weeks of therapy (Liamis 2008). Furthermore, thiazide and thi-
than 130/80 mm Hg after a stroke, which is in line with other CV azide-like diuretics can induce hyponatremia through natri-
conditions (Kleindorfer 2021). Thiazide diuretics, ACE inhib- uresis. Of note, this can lead to counterbalance measures to
itors, and ARBs have shown effectiveness in lowering blood retain sodium, such as increasing angiotensin II and aldoste-
pressure in this population and in reducing the risk of stroke rone. Because of this, the timing of hyponatremia occurrence
recurrence (Zonneveld 2018). Therefore, these agents should can be variable, with studies showing it can occur after years
be prioritized as initial antihypertensive therapy in patients of diuretic therapy (Barber 2015; Leung 2011). Therefore, fol-
with stroke. Evidence supporting CCBs for secondary stroke low-up monitoring of these electrolytes within 2 to 4 weeks
risk protection is limited. However, CCBs remain safe for use in upon initiation or dose titration is necessary, and routine mon-
patients with stroke, making them reasonable as add-on ther- itoring every 12 months can be done once the diuretic regi-
apy for patients requiring additional blood pressure–lowering men has been maintained. Dose reduction or discontinuation
medications. of the diuretic can effectively resolve hypokalemia. However, if
diuretic therapy is necessary, clinicians should consider com-
Managing Adverse Effects bining therapy with a RAS inhibitor, such as an ACE inhibitor or
Adverse effects with antihypertensive agents are common, ARB. This combination may help mitigate potassium depletion
with an estimated 20% of patients experiencing side effects and counterbalance the increase in angiotensin II and aldoste-
with treatment (Bardage 2000). Furthermore, adverse effects rone (Liamis 2008). Dietary modifications to increase potas-
have been identified as one of the main factors contribut- sium intake can be an option, though they may not fully replace
ing to treatment nonadherence and discontinuation (Tedla potassium loss. Potassium supplementation, together with
2016; Grégoire 2002). Adverse effects from antihypertensive

PSAP 2025 Book 1 • Cardiology 13 Hypertension

dietary changes, may be more effective in reversing diuretic-in- Other Considerations
duced hypokalemia (Cohn 2000). Hypertension in Pregnancy
The 2021 International Society for the Study of Hyperten-
Edema
sion in Pregnancy guidelines recommend treating to a DBP
Peripheral edema is a common side effect with dihydropyri- less than 85 mm Hg in the setting of non-severe hyperten-
dine CCBs, affecting up to 70% of patients (Sica 2003). Periph- sion, regardless of the SBP. Pregnant women presenting with
eral edema is often dose-dependent and affects the lower a severely elevated SBP of 160 mm Hg or greater should be
extremities. Calcium channel blocker–induced edema is treated with antihypertensive agents to get the SBP lower than
resistant to diuretics because the mechanism is unrelated to 160 mm Hg. Labetalol, methyldopa, and nifedipine are recom-
salt and water retention and is primarily because of the imbal- mended first line for non-severe hypertension (Magee 2022).
ance of pre- and postcapillary dilation leading to leakage of Angiotensin-converting enzyme inhibitors, ARBs, and direct
intravascular plasma (Skovbjerg 2023; Sica 2003). Dose renin inhibitors should be avoided because of fetal toxicity,
reduction or discontinuation of the offending agent is effec- particularly in the second and third trimesters. Appropriate
tive in resolving peripheral edema with dihydropyridine CCBs. management is critical because uncontrolled hypertension
Changing to a non-dihydropyridine CCB or initiating an ACE can cause eclampsia and premature birth as well as increase
inhibitor or ARB reduces the risk of CCB-induced peripheral the risk of CV events for the mother (Magee 2022).
edema. If the patient is already taking an ACE inhibitor or ARB,
increasing the dose of the ACE inhibitor or ARB has also been Evening Dosing of Antihypertensive Agents
shown effective if the patient can tolerate the dose increase In general, antihypertensives are taken in the morning because
(Skovbjerg 2023). research suggests that morning administration improves
adherence compared with evening administration (Phillips
Erectile Dysfunction 2021). However, controversy over the optimal timing of antihy-
Thiazide diuretics, nonselective β-blockers, and MRAs have pertensive agents began to increase over the past 2 decades
been associated with erectile dysfunction. These agents when data from several studies suggested that evening admin-
seem to negatively affect penile vasculature. Whether this is istration improves blood pressure control and reduces the risk
a true cause-and-effect relationship is unknown (Viigimaa of CV outcomes compared with morning administration (Her-
2020). Evidence suggests that certain antihypertensive mida 2020, 2011). The proposed benefit of evening adminis-
agents have neutral or beneficial effects on erectile dysfunc- tration stems from the potential increased risk of adverse CV
tion in patients with hypertension. Several studies have found outcomes among individuals with non-dipping blood pressure
that ARBs, when compared with β-blockers, can improve patterns (Fagard 2009). This controversy has since subsided
erectile dysfunction, particularly when used in combination with the recent publication of the Treatment in the Morning
with a phosphodiesterase type 5 (PDE-5) inhibitor (Chrysant versus Evening (TIME) trial in 2022, which found no signifi-
2015). Therefore, changing antihypertensive treatment to an cant difference in the composite end point of vascular death
ARB may help improve erectile dysfunction. Nebivolol, a third- or hospitalization for nonfatal MI or nonfatal stroke with eve-
generation β-blocker, has a secondary activity to cause vaso- ning dosing compared with morning dosing of antihyperten-
dilation through nitric oxide production. Studies have indicated sive medications (3.4% vs 3.7%; HR 0.95; 95% CI, 0.83-1.10;
that nebivolol is less associated with erectile dysfunction than P = .53). Of note, more study withdrawals occurred in the eve-
other β-blockers, including atenolol, bisoprolol, carvedilol, and ning dosing group (62.7%) than in the morning dosing group
metoprolol (Chrysant 2015). Thus, clinicians could consider (37.3%) (Mackenzie 2022).
using nebivolol as the β-blocker of choice among patients After publication of the TIME trial, ISH released a consen-
who are at risk of or currently experiencing erectile dysfunc- sus document, endorsed by the World Hypertension League
tion (Viigimaa 2020). The PDE-5 inhibitors are commonly used and ESH, which summarized the current literature and pro-
to treat erectile dysfunction, and studies have shown that they vided recommendations surrounding the timing of antihy-
are safe and effective in patients with hypertension (Mano- pertensive administration (Stergiou 2022). The consensus
lis 2012). However, cautious use of PDE-5 inhibitors is imper- document states evening administration of antihyperten-
ative when paired with α-blockers because of the increased sives should not be routinely recommended in clinical prac-
risk of orthostatic hypotension. Of note, PDE-5 inhibitors are tice, and instead, notes that the long-acting antihypertensive
contraindicated with concomitant use of nitrates because of medications should be used to achieve 24-hour blood pres-
the risk of severe symptomatic hypotension. This is usually a sure control. The 2023 ESH guidelines provide similar rec-
concern in the acute setting, where nitrates are often adminis- ommendations, stating morning administration and evening
tered (Viigimaa 2020). administration have similar outcomes in the general popula-
tion (Mancia 2023). Therefore, patients should be advised to
take their medications at a time that best suits their schedule

PSAP 2025 Book 1 • Cardiology 14 Hypertension

 Patient Care Scenario
A 65-year-old man comes to his primary care physician’s pressures over the past month have ranged from 128 to
office for a routine follow-up for hypertension manage- 135/73 to 78 mm Hg. He reports good adherence to his
ment. His only pertinent medical history is hypertension medications and lifestyle modifications. He denies any
for the past 10 years, for which he has been taking hydro- side effects from his medications. Laboratory test results
chlorothiazide 25 mg and losartan 50 mg once daily in the show serum sodium 140 mEq/L, serum potassium 4.2
morning. Six months ago, his blood pressure at the clinic mEq/L, and SCr 0.8 mg/dL. How should this patient’s
was 129/72 mm Hg. Today, his blood pressure is 138/75 hypertension be managed?
mm Hg with a pulse rate of 72 beats/min. His home blood
ANSWER
The first step in managing this patient’s hypertension is Given the patient’s blood pressure readings, his hyper-
to confirm the accuracy of the blood pressure obtained in tension appears to be inadequately controlled, given
the clinic. Clinicians should ensure that the patient was that his blood pressure today is above the target goal of
resting for at least 5 minutes before the blood pressure less than 130/80 mm Hg. His serum sodium and potas-
measurement and that the appropriate cuff size was used. sium concentrations are within normal limits, indicating
Furthermore, if the blood pressure was obtained manu- no evidence of electrolyte disturbances related to his
ally, remeasuring the patient’s blood pressure using an current antihypertensive regimen. Although hydrochloro-
AOBP machine is advisable. This will allow the clinician thiazide is widely used in clinical practice, chlorthalidone
to obtain an unattended blood pressure reading, helping and indapamide usually have longer half-lives and may
to rule out possible white-coat effect. be more potent. Therefore, changing hydrochlorothiazide
in favor of chlorthalidone or indapamide could be con-
Next, clinicians should thoroughly assess adherence to
sidered. Alternatively, titrating the losartan dose to the
medication regimens and lifestyle modifications at every
maximum effective dose of 100 mg (divided into one or
visit. Furthermore, potential secondary causes of his ele-
two doses) could be advised. Because an adjustment to
vated blood pressure should be identified. Medications
the patient’s antihypertensive regimen was made, a basic
that can increase blood pressure should be evalu-
metabolic panel to monitor serum potassium concentra-
ated, particularly in patients with previously controlled
tion and kidney function should be ordered within 2 to
blood pressure. Common medications that can increase
4 weeks of regimen adjustment. The recommended fol-
blood pressure include NSAIDs, decongestants, and
low-up interval to reassess his blood pressure is 4 weeks.
antidepressants.

Information from Whelton 2018, Ishani 2022.

to maximize adherence, in addition to considering the use of not met the blood pressure goal of less than 130/80 mm Hg
long-acting antihypertensive agents. after 6 months of lifestyle therapy. Considerations for antihy-
pertensive therapy can also be given in young adult patients
Stage 1 Hypertension with Low CV Risk with stage 1 hypertension at elevated risk, such as having a
The 2017 ACC/AHA hypertension guidelines recommend family history of premature CVD, history of gestational hyper-
initiating lifestyle interventions first in patients with stage 1 tension, or personal history of premature birth.
hypertension with low CV risk (10-year risk of ASCVD less
than 10%) and reassessing blood pressure in 3 to 6 months HYPERTENSIVE CRISIS
(Whelton 2018). Limited clinical trial data exist in patients with Hypertensive crises include hypertensive emergency and
stage 1 hypertension and low 10-year CV risk because of the hypertensive urgency. Both are characterized by markedly
feasibility of conducting outcomes trials in this patient pop- elevated blood pressure (SBP greater than 180 mm Hg and/
ulation. Therefore, guidelines relied on evidence from other or DBP greater than 120 mm Hg), but they differ depending on
types of studies, such as population-based studies, which led the presence or absence of target organ damage and treat-
to gaps in recommendations for this patient population. To ment (Mancia 2023). Differentiating between hypertensive
meet this guidance gap, the AHA published a scientific state- emergency and urgency is important to determine the appro-
ment in 2021 to provide clarity in the management of hyper- priate action and use of resources; hypertensive emergency
tension in patients with stage 1 hypertension with low CV risk requires immediate treatment, whereas hypertensive urgency
whose disease remains uncontrolled after 6 months of life- may not require treatment at all.
style therapy (Jones 2021). The scientific statement suggests It is critical that patients with hypertension have a way to
that clinicians should consider initiating an antihypertensive check their blood pressure at home, and clinicians should
agent from one of the 4 first-line therapy classes (ACE inhibi- instruct patients with hypertension to seek immediate med-
tor, ARB, CCB, thiazide/thiazide-like diuretic) if patients have ical care if their blood pressure is 180/120 mm Hg or higher

PSAP 2025 Book 1 • Cardiology 15 Hypertension

and they are experiencing chest pain, shortness of breath, or more antihypertensives at their maximally tolerated doses,
signs of a stroke (eg, difficulty speaking, numbness, weak- most commonly including a diuretic, CCB, and ACE inhibitor
ness, vision changes) (American Heart Association 2024). or ARB (Carey 2018). Refractory hypertension represents an
extreme form of resistance and is characterized by uncon-
Hypertensive Emergency trolled blood pressure despite maximal therapy with at least
Hypertensive emergency is diagnosed when blood pressure 5 antihypertensives, including a long-acting thiazide/thia-
is severely elevated, and evidence of target organ damage zide-like diuretic and an MRA (Matanes 2022). Resistant
(eg, acute coronary syndrome, acute kidney injury, eclampsia, hypertension is estimated to affect 12% to 18% of individu-
encephalopathy, stroke) is present. Of note, blood pressure als with hypertension (Carey 2018). Refractory hypertension
readings greater than 170/110 mm Hg in pregnant patients are is less common, with an estimated prevalence of less than
also classified as a hypertensive emergency (Mancia 2023). 5% among individuals with resistant hypertension (Acelajado
Hypertensive emergency can be life threatening and should 2019). Evaluation of both resistant and refractory hyperten-
be managed in the ICU to allow for continuous monitoring of sion involves first ruling out pseudo-resistance, which may
blood pressure and target organ damage, as well as adminis- arise from factors such as medication nonadherence, white-
tration of intravenous antihypertensives (Whelton 2018). coat hypertension, or inaccurate blood pressure measure-
The rate of desired blood pressure lowering is based on the ment technique (Carey 2018). Treatment inertia can also occur
presence or absence of a compelling indication, such as aor- when clinicians do not initiate or intensify the antihyperten-
tic dissection, severe preeclampsia, eclampsia, or pheochro- sive regimen when therapeutic goals are not met. Therefore,
mocytoma crisis. For those with a compelling indication, the treatment inertia should also be evaluated, given that most
goal SBP is less than 140 mm Hg in the first hour. For aor- patients with apparent treatment-resistant hypertension are
tic dissection specifically, the goal is less than 120 mm Hg. If taking suboptimal antihypertensive regimens. Furthermore, a
there is not a compelling indication, goal SBP reduction within comprehensive evaluation for secondary causes of hyperten-
the first hour is no more than 25%. If the patient remains sta- sion such as primary aldosteronism, obstructive sleep apnea,
ble, blood pressure can be lowered to normal over 1 or 2 days. and other medications known to increase blood pressure is
Although evidence guiding the choice of pharmacotherapy important in identifying and addressing underlying etiologies
for hypertensive emergency is limited, short-acting titratable contributing to treatment resistance.
antihypertensives (eg, nicardipine, nitroprusside, hydrala-
zine, esmolol, labetalol) are often preferred to prevent addi- Management Strategies
tional target organ damage. In the 2017 ACC/AHA guidelines, Management of resistant and refractory hypertension encom-
table 19 provides additional information on specific medica- passes a comprehensive and individualized approach. If fac-
tions used for hypertensive emergencies according to spe- tors contributing to pseudoresistance are identified, clinicians
cific organ involvement and comorbidities (Whelton 2018). should focus on addressing them, which may include opti-
mizing medication adherence, ensuring appropriate blood
Hypertensive Urgency pressure measurement techniques, and intensifying lifestyle
If patients experience severe blood pressure elevation without modifications (Carey 2018). For treatment inertia, clinicians
evidence of target organ damage, they are classified as having should consider titrating doses of antihypertensives to their
hypertensive urgency. This is often caused by discontinuing recommended maximally effective dose, provided patients
prescribed antihypertensives, and treatment includes reinitiat- can tolerate the higher doses. In addition, considerations
ing or intensifying therapy. If patients have not already been should be made to ensure regimens are using the optimal
prescribed an antihypertensive, a dihydropyridine CCB can be antihypertensives, which includes changing hydrochlorothia-
used while secondary causes of hypertension are explored zide to a more potent and longer-acting thiazide-like diuretic
because these agents are usually well tolerated and do not (eg, chlorthalidone or indapamide). Moreover, drugs known
interfere with diagnostic tests for secondary hypertension to elevate blood pressure should be evaluated for necessity
(Mancia 2023; Whelton 2018). Anxiety may also need to be and should promptly be discontinued if deemed unnecessary
addressed. Hypertensive urgency can and should be treated by clinicians. For refractory hypertension, referral to a hyper-
in the outpatient setting with oral medications, and blood pres- tension specialist for further evaluation and consideration
sure should be gradually lowered over 1 or 2 days (Mancia of alternative medical therapies, such as renal denervation
2023). or device-based interventions, may be necessary (Matanes
2022).
RESISTANT AND REFRACTORY The PATHWAY-2 trial supports the use of MRAs as the
HYPERTENSION fourth agent to be added in cases of true resistant hyperten-
sion. The trial was a multicenter, double-blind, randomized,
Definition and Diagnostic Criteria
controlled crossover trial that found significant benefits for
Resistant hypertension is defined as blood pressure that spironolactone on SBP reduction compared with doxazosin
remains above goal despite the concurrent use of three or

PSAP 2025 Book 1 • Cardiology 16 Hypertension

(–4.03 mm Hg), bisoprolol (–4.48 mm Hg), and placebo (–8.70 Hg or greater despite taking three antihypertensives from dif-
mm Hg) among patients with resistant hypertension man- ferent pharmacologic classes. Seven hundred thirty partici-
aged with a diuretic, CCB, and ACE inhibitor or ARB (Williams pants were randomized to receive aprocitentan or placebo for
2015). If intolerance or contraindications prevent the addition 48 weeks, which was divided into 3 parts. During the first 4
of an MRA, alternative second-line antihypertensives such as weeks, participants were randomized to double-blind treat-
β-blockers, α-blockers, and vasodilators can be considered. ment with aprocitentan 12.5 mg, aprocitentan 25 mg, or pla-
In 2024, the FDA approved aprocitentan, a dual endothelin cebo in a 1:1:1 ratio. The second part consisted of a 32-week
receptor antagonist, for the treatment of hypertension in com- single-blind phase in which all patients received aprocitentan
bination with other antihypertensives. Aprocitentan prevents 25 mg. The third part was a withdrawal phase that consisted
the binding of endothelin-1, a potent vasoconstrictor peptide, of re-randomizing participants to aprocitentan 25 mg or pla-
to both endothelin A and endothelin B receptors, thereby pre- cebo in a double-blind 1:1 ratio for 12 weeks. The primary and
venting its effect to constrict blood vessels and increase blood key secondary end points, respectively, were changes in unat-
pressure (Angeli 2021). Aprocitentan was approved on the tended office SBP from baseline to week 4 (part 1) and from
basis of data gathered from the Parallel-Group, Phase 3 Study withdrawal phase (week 36) baseline to week 40 (part 3). The
with Aprocitentan in Subjects with Resistant Hypertension study found significant differences in the change in office SBP
(PRECISION), which evaluated the blood pressure–lowering at 4 weeks with both doses of aprocitentan (mean change –3.8
effect of aprocitentan in patients with resistant hypertension ± 1.3 mm Hg with aprocitentan 12.5 vs placebo [P = .0042] and
(Schlaich 2022). The study was a multicenter, blind, random- mean change –3.7 ± 1.3 mm Hg with aprocitentan 25 mg vs
ized, parallel-group trial conducted in health care centers placebo [P = .0046]). From withdrawal phase (week 36) base-
in Europe, North America, Asia, and Australia. Participants line to week 40, there was a significant increase in the office
were eligible for the study if their seated SBP was 140 mm SBP when participants were transitioned to placebo com-
pared with those who continued aprocitentan (mean change
+5.8 mm Hg [95% CI, 3.7-7.9; P < .0001]). The most common
Practice Points adverse event in the study was edema or fluid retention, which
Clinical pharmacists play a pivotal role in the man- occurred prominently during the first 4 weeks of treatment,
agement of hypertension. As medication experts, with higher doses showing a higher prevalence (2.1% with pla-
pharmacists are well positioned to optimize treatment cebo, 9.1% with aprocitentan 12.5 mg, and 18.4% with aproci-
outcomes for patients with hypertension by implement- tentan 25 mg). The authors concluded that aprocitentan was
ing the latest evidence and practice guidelines.
well tolerated and effective in lowering SBP in patients with
• Initial assessment of elevated blood pressure should treatment-resistant hypertension (Schlaich 2022). However, it
include evaluation for secondary causes when indicated,
is not yet known where aprocitentan will fit into the therapeu-
use of both in-office and out-of-office blood pressure mea-
tic landscape because there are currently no head-to-head
surements, and consideration for masked and white-coat
hypertension. studies comparing it with other add-on agents for resistant
• The optimal blood pressure goal for most patients is less hypertension, particularly MRAs, which are usually consid-
than 130/80 mm Hg. Individualized factors should be ered first line for resistant hypertension.
considered in populations prone to side effects related
to antihypertensive treatment (eg, older adults with high
comorbidity burden).
CONCLUSION
• Lifestyle interventions are integral to appropriate hyper- Effective management of hypertension involves a multifac-
tension management, and multifaceted patient-specific eted approach encompassing lifestyle modifications, phar-
counseling should be provided. macotherapy, and regular monitoring to achieve optimal
• First-line pharmacotherapy for hypertension management
blood pressure control and reduce the risk of CV outcomes.
includes an angiotensin-converting enzyme (ACE) inhibitor
or angiotensin receptor blocker (ARB), thiazide diuretic, Pharmacists play a crucial role in hypertension management
calcium channel blocker (CCB), or a combination of these. by providing education on lifestyle modifications, conducting
Choice of pharmacotherapy should be based on magnitude medication reviews, and assessing medication adherence.
of blood pressure elevation and patient comorbidities. Collaboration with other health care providers is critical to
Efforts should be made to minimize adverse effects and
develop personalized treatment plans tailored to individual
avoid drug-drug interactions.
• Second-line pharmacotherapy, such as β-blockers and
patient characteristics and comorbidities. As experts in phar-
mineralocorticoid receptor antagonists (MRAs), should be macotherapy and patient-centered care, pharmacists can sig-
considered in patients with uncontrolled blood pressure de- nificantly contribute to improving hypertension outcomes and
spite use of first-line agents and/or in specific populations overall CV health.
with a compelling indication.
• Administration time of antihypertensives should be person-
alized for each patient, with consideration given to morning
administration to improve adherence.

PSAP 2025 Book 1 • Cardiology 17 Hypertension

REFERENCES Bardage C, Isacson DG. Self-reported side-effects of
antihypertensive drugs: an epidemiological study
Acelajado MC, Hughes ZH, Oparil S, Calhoun DA. Treat-
on prevalence and impact on health-state util-
ment of resistant and refractory hypertension. Circ
ity. Blood Press. 2000;9(6):328-334. [Link]
Res. 2019;124(7):1061-1070. [Link]
org/10.1080/080370500300000905
CIRCRESAHA.118.312156
Beeftink MM, van der Sande NG, Bots ML, et al. Safety of
Agarwal R, Sinha AD, Cramer AE, et al. Chlorthalidone for
temporary discontinuation of antihypertensive medica-
hypertension in advanced chronic kidney disease. N Engl
tion in patients with difficult-to-control hypertension.
J Med. 2021;385(27):2507-2519. [Link]
Hypertension. 2017;69(5):927-932. [Link]
NEJMoa2110730
HYPERTENSIONAHA.116.08793
ALLHAT Officers and Coordinators for the ALLHAT
Boffa RJ, Constanti M, Floyd CN, Wierzbicki AS. Hyperten-
Collaborative Research Group. The antihypertensive and
sion in adults: summary of updated NICE guidance. BMJ.
lipid-lowering treatment to prevent heart attack trial. Major
2019;367:I5310. [Link]
outcomes in high-risk hypertensive patients random-
ized to angiotensin-converting enzyme inhibitor or cal- Brouwer TF, Vehmeijer JT, Kalkman DN, et al. Intensive blood
cium channel blocker vs diuretic: the Antihypertensive and pressure lowering in patients with and patients without
Lipid-Lowering Treatment to Prevent Heart Attack Trial type 2 diabetes: a pooled analysis from two randomized
(ALLHAT). JAMA. 2002;288(23):2981-2997. [Link] trials. Diabetes Care. 2018;41(6):1142-1148. [Link]
org/10.1001/jama.288.23.2981 org/10.2337/dc17-1722
American Academy of Family Physicians. Guidelines devel- Buckley LF, Dixon DL, Wohlford GF 4th, Wijesinghe DS,
oped by external organizations not endorsed by the Baker WL, Van Tassell BW. Intensive versus standard
AAFP. Accessed May 8, 2024. [Link] blood pressure control in SPRINT-eligible participants of
family-physician/patient-care/clinical-recommendations/ ACCORD-BP. Diabetes Care. 2017;40(12):1733-1738. https://
[Link] [Link]/10.2337/dc17-1366
American Diabetes Association Professional Practice Bundy JD, Li C, Stuchlik P, et al. Systolic blood pressure
Committee. 10. Cardiovascular disease and risk manage- reduction and risk of cardiovascular disease and mor-
ment: Standards of Care in Diabetes—2024. Diabetes Care. tality: a systematic review and network meta-analysis.
2024;47(suppl_1):S179-S218. [Link] JAMA Cardiol. 2017;2(7):775-781. [Link]
dc24-S010 jamacardio.2017.1421
American Heart Association. When to call 911 about high Calhoun DA, Jones D, Textor S, et al. Resistant hyperten-
blood pressure. 2024. Accessed July 23, 2024. https:// sion: diagnosis, evaluation, and treatment. A scientific
[Link]/en/health-topics/high-blood-pressure/ statement from the American Heart Association Profes-
understanding-blood-pressure-readings/hypertensive-cris sional Education Committee of the Council for High Blood
is-when-you-should-call-911-for-high-blood-pressure Pressure Research. Hypertension. 2008;51(6):1403-1419.
[Link]
American Medical Association. Home blood pressure
monitoring. 2024. Accessed July 17, 2024. https:// Carey RM, Calhoun DA, Bakris GL, et al. Resistant hyper-
[Link]/en/health-topics/high-blood-pres- tension: detection, evaluation, and management: a sci-
sure/understanding-blood-pressure-readings/ entific statement from the American Heart Association.
monitoring-your-blood-pressure-at-home Hypertension. 2018;72(5):e53-e90. [Link]
HYP.0000000000000084
American Medical Association. US blood pressure validated
device listing. 2023. Accessed July 17, 2024. [Link] CDC. Hypertension cascade: hypertension prevalence, treat-
[Link]/ ment and control estimates among U.S. adults aged 18
years and older applying the criteria from the American
Angeli F, Verdecchia P, Reboldi G. Aprocitentan, a
College of Cardiology and American Heart Association’s
dual endothelin receptor antagonist under develop-
2017 hypertension guideline—NHANES 2017–2020. May
ment for the treatment of resistant hypertension. Car-
12, 2023. Accessed July 6, 2023. [Link]
diol Ther. 2021;10(2):397-406. [Link]
gov/data-reports/hypertension-prevalence_2018.html
s40119-021-00233-7
Chan You S, Krumholz HM, Suchard MA, et al. Compre-
Bakris GL, Weir MR. Angiotensin-converting enzyme inhib-
hensive comparative effectiveness and safety of first-
itor-associated elevations in serum creatinine: is this a
line β-blocker monotherapy in hypertensive patients:
cause for concern? Arch Intern Med. 2000;160(5):685-693.
a large-scale multicenter observational study. Hyper-
[Link]
tension. 2021;77(5):1528-1538. [Link]
Barber J, McKeever TM, McDowell SE, et al. A system- HYPERTENSIONAHA.120.16402
atic review and meta-analysis of thiazide-induced hypo-
Chen C, Zhu XY, Li D, Lin Q, Zhou K. Clinical efficacy and
natraemia: time to reconsider electrolyte monitoring
safety of spironolactone in patients with resistant hyper-
regimens after thiazide initiation? Br J Clin Pharmacol.
tension: a systematic review and meta-analysis. Medicine
2015;79(4):566-577. [Link]

PSAP 2025 Book 1 • Cardiology 18 Hypertension

 (Baltimore). 2020;99(34):e21694. [Link] dipping pattern as predictors of death and cardiovascular
md.0000000000021694 events in hypertension. J Hum Hypertens. 2009;23(10):645-
653. [Link]
Cheung AK, Chang TI, Cushman WC, et al. for the Kidney Dis-
ease: Improving Global Outcomes (KDIGO) Blood Pressure Fatani N, Dixon DL, Van Tassell BW, Fanikos J, Buckley LF.
Work Group. KDIGO 2021 clinical practice guideline for the Systolic blood pressure time in target range and cardio-
management of blood pressure in chronic kidney disease. vascular outcomes in patients with hypertension. J Am Coll
Kidney Int. 2021;99(3S):S1-S87. [Link] Cardiol. 2021;77(10):1290-1299. [Link]
kint.2020.11.003 jacc.2021.01.014

Cheung AK, Rahman M, Reboussin DM, et al. Effects of inten- Fretheim A, Odgaard-Jensen J, Brørs O, et al. Compara-
sive BP control in CKD. J Am Soc Nephrol. 2017;28(9):2812- tive effectiveness of antihypertensive medication for pri-
2823. [Link] mary prevention of cardiovascular disease: systematic
review and multiple treatments meta-analysis. BMC Med.
Chrysant SG. Antihypertensive therapy causes erectile dys- 2012;10(1):33. [Link]
function. Curr Opin Cardiol. 2015;30(4):383-390. [Link]
org/10.1097/HCO.0000000000000189 GBD 2019 Risk Factors Collaborators. Global burden of 87
risk factors in 204 countries and territories, 1990-2019:
Cohn JN, Kowey PR, Whelton PK, Prisant LM. New guide- a systematic analysis for the Global Burden of Disease
lines for potassium replacement in clinical practice: a con- Study 2019. Lancet. 2020;396(10258):1223-1249. https://
temporary review by the National Council on Potassium in [Link]/10.1016/S0140-6736(20)30752-2
Clinical Practice. Arch Intern Med. 2000;160(16):2429-2436.
[Link] Gorostidi M, Vinyoles E, Banegas JR, de la Sierra A. Preva-
lence of whitecoat and masked hypertension in national
Currie G, Taylor AH, Fujita T, et al. Effect of mineralocorti- and international registries. Hypertens Res. 2015;38(1):1-7.
coid receptor antagonists on proteinuria and progres- [Link]
sion of chronic kidney disease: a systematic review and
meta-analysis. BMC Nephrol. 2016;17(1):127. [Link] Grégoire JP, Moisan J, Guibert R, et al. Determinants of dis-
org/10.1186/s12882-016-0337-0 continuation of new courses of antihypertensive medica-
tions. J Clin Epidemiol. 2002;55(7):728-735. [Link]
Cushman WC, Evans GW, Byington RP, et al; for the ACCORD org/10.1016/s0895-4356(02)00400-6
Study Group. Effects of intensive blood-pressure control in
type 2 diabetes mellitus. N Engl J Med. 2010;362(17):1575- Heidenreich PA, Bozkurt B, Aguilar D, et al. 2022 AHA/ACC/
1585. [Link] HFSA guideline for the management of heart failure: a
report of the American College of Cardiology/American
Dixon DL, Baker WL, Buckley LF, Salgado TM, Van Tassell Heart Association Joint Committee on Clinical Practice
BW, Carter BL. Effect of a physician/pharmacist collabora- Guidelines. Circulation. 2022;145(18):e895-e1032. https://
tive care model on time in target range for systolic blood [Link]/10.1161/CIR.0000000000001063
pressure: post hoc analysis of the CAPTION trial. Hyper-
tension. 2021;78(4):966-972. [Link] Hermida RC, Ayala DE, Mojón A, et al. Bedtime dosing of anti-
HYPERTENSIONAHA.121.17873 hypertensive medications reduces cardiovascular risk in
CKD. J Am Soc Nephrol. 2011;22(12):2313-2321. [Link]
Egan BM, Basile JN, Rehman SU, et al. Plasma renin test- org/10.1681/ASN.2011040361
guided drug treatment algorithm for correcting patients
with treated but uncontrolled hypertension: a random- Hermida RC, Crespo JJ, Domínguez-Sardiña M, et al; Hygia
ized controlled trial. Am J Hypertens. 2009;22(7):792-801. Project Investigators. Bedtime hypertension treatment
[Link] improves cardiovascular risk reduction: the Hygia chrono-
therapy trial. Eur Heart J. 2020;41(48):4565-4576. https://
Emdin CA, Rahimi K, Neal B, Callender T, Perkovic V, Patel [Link]/10.1093/eurheartj/ehz754
A. Blood pressure lowering in type 2 diabetes: a system-
atic review and meta-analysis. JAMA. 2015;313(6):603-615. Huck DM, Rosenberg MA, Stauffer BL. Nebivolol and inci-
[Link] dent cardiovascular events in hypertensive patients
compared with nonvasodilatory beta blockers. J Hyper-
Ernst ME, Fravel MA. Thiazide and the thiazide-like diuret- tens. 2022;40(5):1019-1029. [Link]
ics: review of hydrochlorothiazide, chlorthalidone, and HJH.0000000000003109
indapamide. Am J Hypertens. 2022;35(7):573-586. https://
[Link]/10.1093/ajh/hpac048 Hundemer GL, Sood MM. Hyperkalemia with RAAS inhibi-
tion: mechanism, clinical significance, and management.
Ettehad D, Emdin CA, Kiran A, et al. Blood pressure low- Pharmacol Res. 2021;172:105835. [Link]
ering for prevention of cardiovascular disease and phrs.2021.105835
death: a systematic review and meta-analysis. Lan-
cet. 2016;387(10022):957-967. [Link] Ishani A, Cushman WC, Leatherman SM, et al. Chlorthalidone
S0140-6736(15)01225-8 vs. hydrochlorothiazide for hypertension-cardiovascular
events. N Engl J Med. 2022;387(26):2401-2410. [Link]
Fagard RH, Thijs L, Staessen JA, Clement DL, De Buyzere org/10.1056/NEJMoa2212270
ML, De Bacquer DA. Night–day blood pressure ratio and

PSAP 2025 Book 1 • Cardiology 19 Hypertension

Jones DW, Whelton PK, Allen N, et al. Management of stage Lancet. 2002;360(9349):1903-1913. [Link]
1 hypertension in adults with a low 10-year risk for car- s0140-6736(02)11911-8
diovascular disease: filling a guidance gap: a scientific
statement from the American Heart Association. Hyper- Liamis G, Milionis H, Elisaf M. Blood pressure
tension. 2021;77(6):e58-e67. [Link] drug therapy and electrolyte disturbances. Int
HYP.0000000000000195 J Clin Pract. 2008;62(10):1572-1580. [Link]
org/10.1111/j.1742-1241.2008.01860.x
Kario K, Okada K, Kato M, et al. Twenty-four-hour blood pres-
sure–lowering effect of a sodium-glucose cotransporter 2 Mackenzie IS, Rogers A, Poulter NR, et al; for the TIME Study
inhibitor in patients with diabetes and uncontrolled noctur- Group. Cardiovascular outcomes in adults with hyperten-
nal hypertension: results from the randomized, placebo- sion with evening versus morning dosing of usual anti-
controlled SACRA study. Circulation. hypertensives in the UK (TIME study): a prospective,
2019;139(18):2089-2097. [Link] randomized, open-lab, blinded-endpoint clinical trial. Lan-
CIRCULATIONAHA.118.037076 cet. 2022;400(10361):1417-1425. [Link]
S0140-6736(22)01786-X
Kario K, Tomitani N, Okawara Y, Kanegae H, Hoshide S. Home
systolic blood pressure time in therapeutic range and car- Magee LA, Brown MA, Hall DR, et al. The 2021 International
diovascular risk: the practitioner-based nationwide J-HOP Society for the Study of Hypertension in Pregnancy clas-
study extended. Hypertens Res. 2024;47(1):112-119. https:// sification, diagnosis & management recommendations for
[Link]/10.1038/s41440-023-01416-6 international practice. Pregnancy Hypertens. 2022;27:148-
169. [Link]
Katsanos AH, Filippatou A, Manios E, et al. Blood pressure
reduction and secondary stroke prevention: a systematic Mancia G, Kreutz R, Brunström M, et al. 2023 ESH guidelines
review and metaregression analysis of randomized clin- for the management of arterial hypertension The Task
ical trials. Hypertension. 2017;69(1):171-179. [Link] Force for the management of arterial hypertension of the
org/10.1161/HYPERTENSIONAHA.116.08485 European Society of Hypertension: endorsed by the Inter-
national Society of Hypertension (ISH) and the European
Kimura W, Minatoguchi S, Mizuno T, et al. Sodium zirconium Renal Association (ERA). J Hypertens. 2023;41(12):1874-
cyclosilicate reconciles management of hyperkalemia and 2071. [Link]
continuity of renin-angiotensin-aldosterone system inhibitors:
a retrospective observational study. J Nephrol. 2024;37(1):171- Manolis A, Doumas M. Antihypertensive treatment and sex-
179. [Link] ual dysfunction. Curr Hypertens Rep. 2012;14(4):285-292.
[Link]
Kirkland EB, Heincelman M, Bishu KG, et al. Trends in healthcare
expenditures among US adults with hypertension: national Margolis KL, O’Connor PJ, Morgan TM, et al. Outcomes of com-
estimates, 2003-2014. J Am Heart Assoc. 2018;7(11):e008731. bined cardiovascular risk factor management strategies in
[Link] type 2 diabetes: the ACCORD randomized trial. Diabetes Care.
2014;37(6):1721-1728. [Link]
Kjeldsen SE, Lund-Johansen P, Nilsson PM, Mancia G. Unat-
tended blood pressure measurements in the systolic blood Matanes F, Khan MB, Siddiqui M, Dudenbostel T, Calhoun D,
pressure intervention trial: implications for entry and Oparil S. An update on refractory hypertension. Curr Hyper-
achieved blood pressure values compared with other trials. tens Rep. 2022;24(7):225-234. [Link]
Hypertension. 2016;67(5):808-812. [Link] s11906-022-01185-6
HYPERTENSIONAHA.116.07257 Mehanna M, Wang Z, Gong Y, et al. Plasma renin activity is a
Kleindorfer DO, Towfighi A, Chaturvedi S, et al. 2021 Guide- predictive biomarker of blood pressure response in Euro-
line for the prevention of stroke in patients with stroke pean but not in African Americans with uncomplicated
and transient ischemic attack: a guideline from the Amer- hypertension. Am J Hypertens. 2019;32(7):668-675. https://
ican Heart Association/American Stroke Association. [Link]/10.1093/ajh/hpz022
Stroke. 2021;52(7):e364-e467. [Link] Muntner P, Carey RM, Gidding S, et al. Potential U.S. popula-
STR.0000000000000375 tion impact of the 2017 American College of Cardiology/
Kostis WJ, Shetty M, Chowdhury YS, Kostis JB. ACE inhib- American Heart Association high blood pressure guideline.
itor-induced angioedema: a review. Curr Hypertens Rep. Circulation. 2018;71(2):109-118. [Link]
2018;20(7):55. [Link] CIRCULATIONAHA.117.032582

Leung AA, Wright A, Pazo V, et al. Risk of thiazide-in- Murty M, Pandey R, Behera S, Jayakrishnan J, Hande V,
duced hyponatremia in patients with hypertension. Am J Behera V. Plasma renin-guided therapy in patients of pri-
Med. 2011;124(11):1064-1072. [Link] mary hypertension on antihypertensives: a prospective
amjmed.2011.06.031 cohort study. J Assoc Physicians India. 2022;70(8):11-12.
[Link]
Lewington S, Clarke R, Qizilbash N, Peto R, Collins R.
Age-specific relevance of usual blood pressure to vas- Muxfeldt ES, Margallo V, Costa LM, et al. Effects of contin-
cular mortality: a meta-analysis of individual data uous positive airway pressure treatment on clinic and
for one million adults in 61 prospective studies. ambulatory blood pressures in patients with obstructive
sleep apnea and resistant hypertension: a randomized

PSAP 2025 Book 1 • Cardiology 20 Hypertension

 controlled trial. Hypertension. 2015;65(4):736-742. https:// 2022;79(12):2685-2695. [Link]
[Link]/10.1161/HYPERTENSIONAHA.114.04852 HYPERTENSIONAHA.122.19744

National Institute for Health and Care Excellence. Hyper- Savarese G, Costanzo P, Cleland JG, et al. A meta-analysis
tension in Adults: Diagnosis and Management, NICE Clinical reporting effects of angiotensin-converting enzyme inhib-
Guideline NG136. 2023. [Link] itors and angiotensin receptor blockers in patients without
ng136 heart failure. J Am Coll Cardiol. 2013;61(2):131-142. https://
[Link]/10.1016/[Link].2012.10.011
Neal B, Wu Y, Feng X, et al. Effect of salt substitution
on cardiovascular events and death. N Engl J Med. Schlaich MP, Bellet M, Weber MA, et al. Dual endothelin
2021;385(12):1067-1077. [Link] antagonist aprocitentan for resistant hypertension (PRECI-
NEJMoa2105675 SION): a multicentre, blinded, randomised, parallel-group,
phase 3 trial. Lancet. 2022;400(10367):1927-1937. https://
Olde Engberink RH, Frenkel WJ, van den Bogaard B, Brew- [Link]/10.1016/S0140-6736(22)02034-7
ster LM, Vogt L, van den Born BJH. Effects of thiazide-type
and thiazide-like diuretics on cardiovascular events and Sica D. Calcium channel blocker-related peripheral edema:
mortality: systematic review and meta-analysis. Hyper- can it be resolved? J Clin Hypertens (Greenwich). 2003;5(4):
tension. 2015;65(5):1033-1040. [Link] 291-297. [Link]
HYPERTENSIONAHA.114.05122
Sica DA, Carter B, Cushman W, Hamm L. Thiazide and loop
Ostchega Y, Fryar CD, Nwankwo T, Nguyen DT. Hypertension diuretics. J Clin Hypertens (Greenwich). 2011;13(9):
prevalence among adults aged 18 and over: United States, 639-643. [Link]
2017–2018. NCHS Data Brief. 2020 Apr;(364):1-8. Accessed
October 31, 2024. [Link] Skovbjerg BK, Helgestad OK, Oxlund CS, et al. Management
briefs/[Link] of amlodipine-induced ankle oedema. Article in Danish.
Ugeskr Laeger. 2023;185:V07220460. [Link]
Perkovic V, Rodgers A. Redefining blood-pressure tar- [Link]/37114573
gets—SPRINT starts the marathon. N Engl J Med.
2015;373(22):2175-2178. [Link] Smith SM, Campbell JD. Cost-effectiveness of renin-
NEJMe1513301 guided treatment of hypertension. Am J Hypertens.
2013;26(11):1303-1310. [Link]
Phillips LA, Burns E, Leventhal H. Time-of-day differences in
treatment-related habit strength and adherence. Ann Behav SPRINT Research Group; Lewis CE, Fine LJ, Beddhu S, et
Med. 2021;55(3):280-285. [Link] al. Final report of a trial of intensive versus standard
kaaa042 blood-pressure control. N Engl J Med. 2021;384(20):1921-
1930. [Link]
Piper MA, Evans CV, Burda BU, Margolis KL, O’Connor
E, Whitlock EP. Diagnostic and predictive accuracy Stergiou GS, Asayama K, Thijs L, et al. Prognosis of white-
of blood pressure screening methods with consider- coat and masked hypertension: international database
ation of rescreening intervals: a systematic review for of home blood pressure in relation to cardiovascular out-
the U.S. Preventive Services Task Force. Ann Intern Med. come. Hypertension. 2014;63(4):675-682. [Link]
2015;162(3):192-204. [Link] org/10.1161/HYPERTENSIONAHA.113.02741

Poorolajal J, Zeraati F, Soltanian AR, Sheikh V, Hooshmand Stergiou G, Brunström M, MacDonald T, et al. Bedtime dos-
E, Maleki A. Oral potassium supplementation for manage- ing of antihypertensive medications: systematic review
ment of essential hypertension: a meta-analysis of ran- and consensus statement: International Society of Hyper-
domized controlled trials. PLoS One. 2017;12(4):e0174967. tension position paper endorsed by World Hypertension
[Link] League and European Society of Hypertension. J Hyper-
tens. 2022;40(10):1847-1858. [Link]
Prabhakaran D, Anand S, Watkins D, et al. Cardiovascu- HJH.0000000000003240
lar, respiratory, and related disorders: key messages
from Disease Control Priorities. 3rd edition. Lancet. Strippoli GF, Craig M, Deeks JJ, Schena FP, Craig JC. Effects
2018;391(10126):1224-1236. [Link] of angiotensin converting enzyme inhibitors and angio-
S0140-6736(17)32471-6 tensin II receptor antagonists on mortality and renal
outcomes in diabetic nephropathy: systematic review.
Roerecke M, Kaczorowski J, Myers MG. Comparing auto- BMJ. 2004;329(7470):828. [Link]
mated office blood pressure readings with other methods bmj.38237.585000.7C
of blood pressure measurement for identifying patients
with possible hypertension: a systematic review and Tedla YG, Bautista LE. Drug side effect symptoms and adher-
meta-analysis. JAMA Intern Med. 2019;179(3):351-362. ence to antihypertensive medication. Am J Hypertens.
[Link] 2016;29(6):772-779. [Link]

Ruilope LM, Agarwal R, Anker SD, et al. Blood pres- Thomopoulos C, Bazoukis G, Tsioufis C, Mancia
sure and cardiorenal outcomes with finerenone in G. Beta-blockers in hypertension: overview and
chronic kidney disease in type 2 diabetes. Hypertension. meta-analysis of randomized outcome trials. J Hyper-
tens. 2020;38(9):1669-1681. [Link]
HJH.0000000000002523

PSAP 2025 Book 1 • Cardiology 21 Hypertension

Thomopoulos C, Parati G, Zanchetti A. Effects of blood pres- Whelton PK, Carey RM, Aronow WS, et al. 2017 ACC/AHA/
sure-lowering on outcome incidence in hypertension. 5. AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA
Head-to-head comparisons of various classes of antihy- guideline for the prevention, detection, evaluation, and
pertensive drugs-overview and meta-analyses. J Hyper- management of high blood pressure in adults: executive
tens. 2015;33(7):1321-1341. [Link] summary: a report of the American College of Cardiology/
HJH.0000000000000614 American Heart Association task force on clinical practice
guidelines. Hypertension. 2018;71(6):1269-1324. [Link]
Thomopoulos C, Parati G, Zanchetti A. Effects of blood-pres- org/10.1161/HYP.0000000000000066
sure-lowering treatment on outcome incidence in hyper-
tension. 10. Should blood pressure management differ Whelton SP, McEvoy JW, Shaw L, et al. Association of
in hypertensive patients with and without diabetes melli- normal systolic blood pressure level with cardiovas-
tus? Overview and meta-analyses of randomized trials. J cular disease in the absence of risk factors. JAMA Car-
Hypertens. 2017;35(5):922-944. [Link] diol. 2020;5(9):1011-1018. [Link]
HJH.0000000000001276 jamacardio.2020.1731

Tseng DS, Kwong J, Rezvani F, Coates AO. Angiotensin-con- Williams B, MacDonald TM, Morant S, et al. Spironolactone
verting enzyme-related cough among Chinese-Americans. versus placebo, bisoprolol, and doxazosin to determine the
Am J Med. 2010;123(2):183.e11-5. [Link] optimal treatment for drug-resistant hypertension (PATH-
amjmed.2009.06.032 WAY-2): a randomised, double-blind, crossover trial. Lan-
cet. 2015;386(10008):2059-2068. [Link]
Unger T, Borghi C, Charchar F, et al. 2020 International Soci- S0140-6736(15)00257-3
ety of Hypertension global hypertension practice guide-
lines. Hypertension. 2020;75(6):1334-1357. [Link] Williamson JD, Pajewski NM, Auchus AP, et al; for SPRINT
org/10.1161/HYPERTENSIONAHA.120.15026 MIND Investigators for the SPRINT Research Group.
Effect of intensive vs standard blood pressure con-
Viigimaa M, Vlachopoulos C, Doumas M, et al. Update of the trol on probable dementia: a randomized clinical trial.
position paper on arterial hypertension and erectile dys- JAMA. 2019;321(6):553-561. [Link]
function. J Hypertens. 2020;38(7):1220-1234. [Link] jama.2018.21442
org/10.1097/HJH.0000000000002382
Williamson JD, Supiano MA, Applegate WB, et al. Intensive
Virani SS, Newby LK, Arnold SV, et al. 2023 AHA/ACC/ vs standard blood pressure control and cardiovascular dis-
ACCP/ASPC/NLA/PCNA guideline for the management ease outcomes in adults aged ≥75 years: a randomized
of patients with chronic coronary disease: a report of the clinical trial. JAMA. 2016;315(24):2673-2682. [Link]
American Heart Association/American College of Car- org/10.1001/jama.2016.7050
diology Joint Committee on clinical practice guidelines.
Circulation. 2023;148(9):e9-e119. [Link] Wilt TJ, Kansagara D, Qaseem A; Clinical Guidelines Commit-
CIR.0000000000001168 tee of the American College of Physicians. Hypertension
limbo: balancing benefits, harms, and patient preferences
Wagner TD, Jones MC, Salgado TM, Dixon DL. Pharmacist’s before we lower the bar on blood pressure. Ann Intern Med.
role in hypertension management: a review of key random- 2018;168(5):369-370. [Link]
ized controlled trials. J Hum Hypertens. 2020;34(7):487-
494. [Link] WHO. Global report on hypertension: the race against a silent
killer. World Health Organization; 2023:1-276. Accessed
Wei J, Galaviz KI, Kowalski AJ, et al. Comparison of cardio- October 30, 2024. [Link]
vascular events among users of different classes of antihy- item/9789240081062
pertension medications: a systematic review and network
meta-analysis. JAMA Netw Open. 2020;3(2):e1921618. Wright JT Jr, Williamson JD, Whelton PK, et al; for the
[Link] SPRINT Research Group. A randomized trial of inten-
sive versus standard blood-pressure control. N Engl J
Weinberg JM, Appel LJ, Bakris G, et al. Risk of hyperka- Med. 2015;373(22):2103-2116. [Link]
lemia in nondiabetic patients with chronic kidney dis- NEJMoa1511939
ease receiving antihypertensive therapy. Arch Intern
Med. 2009;169(17):1587-1594. [Link] Zhang W, Zhang S, Deng Y, et al; for the STEP Study Group.
archinternmed.2009.284 Trial of intensive blood-pressure control in older patients
with hypertension. N Engl J Med. 2021;385(14):1268-1279.
Weintraub HS, Duprez DA, Cushman WC, et al. Antihy- [Link]
pertensive response to thiazide diuretic or angiotensin
receptor blocker in elderly hypertensives is not influ- Zonneveld TP, Richard E, Vergouwen MD, et al. Blood pres-
enced by pretreatment plasma renin activity. Cardiovasc sure-lowering treatment for preventing recurrent stroke,
Drugs Ther. 2012;26(2):145-155. [Link] major vascular events, and dementia in patients with a
s10557-011-6365-x history of stroke or transient ischaemic attack. Cochrane
Database Syst Rev. 2018;7(7):CD007858. [Link]
org/10.1002/14651858.CD007858.pub2

PSAP 2025 Book 1 • Cardiology 22 Hypertension

Self-Assessment Questions
1. A 45-year-old man has a blood pressure averaging C. 2023 ESH guidelines have a higher cardiovascular
128/77 mm Hg across two recent office visits. He is (CV) risk threshold for initiating drug therapy at
asked to check his blood pressure at home and is pro- blood pressure 130/80 mm Hg or greater.
vided instruction about proper measurement technique. D. 2017 ACC/AHA guidelines provide a specific
Three days later, he calls in the following results: 132/88 definition for isolated systolic hypertension.
mm Hg, 144/92 mm Hg, and 134/90 mm Hg. Which one
4. A 72-year-old man with hypertension comes to the pri-
of the following best assesses whether this patient meets
mary care clinic with elevated blood pressure, averaging
the diagnostic criteria for hypertension?
145/75 mm Hg. He takes olmesartan 20 mg once daily
A. Yes, he has sustained hypertension. and amlodipine 5 mg once daily. His primary care pro-
B. Yes, he has masked hypertension. vider is interested in targeting a blood pressure goal of
C. Yes, he has white-coat hypertension. less than 130/80 mm Hg and asks for your recommenda-
D. No, he does not have hypertension. tion. On the basis of available evidence, which one of the
following is the best education point to share with this
2. A 42-year-old man with a medical history of type 2 dia-
colleague regarding the patient’s blood pressure target?
betes (T2D), attention-deficit/hyperactivity disorder, and
general anxiety disorder comes to the clinic. His home A. Lowering systolic blood pressure (SBP) to less than
drugs include metformin 1000 mg by mouth twice daily, 130 mm Hg reduces stroke risk.
semaglutide 2 mg subcutaneously once weekly, lis- B. Lowering SBP to less than 130 mm Hg increases fall
dexamfetamine 70 mg by mouth once daily, and escit- risk.
alopram 10 mg by mouth once daily. He has been taking C. Lowering SBP to less than 130 mm Hg reduces
these drugs at the current doses for the past year. In dementia risk.
addition, he reports experiencing headaches for the past D. Lowering SBP to less than 130 mm Hg increases
2 days, for which he has been taking ibuprofen 200 mg fracture risk.
by mouth once or twice per day. His blood pressure 6
months ago was 134/80 mm Hg, and his blood pressure The next two questions pertain to the following case.
today is 136/82 mm Hg. Which one of the following is Y.G. is a 40-year-old non-Hispanic White man (height 182.88
most likely contributing to this patient’s consistently ele- cm, weight 112.49 kg). His vital signs today in the office include
vated blood pressure? blood pressure 152/96 mm Hg (average of the two readings
A. Escitalopram from today’s office visit and previous office visit), pulse rate
B. Semaglutide 62 beats/min, and respiratory rate 16 breaths/min. Y.G. has
C. Lisdexamfetamine no chronic medical conditions. He reports walking 15 minutes
D. Ibuprofen each day and drinking 4 beers per day. He usually skips break-
fast and eats out most days for lunch. For dinner, he usually
3. A 62-year-old woman comes to her primary care physi-
has a TV dinner, can of soup, or deli sandwich.
cian for a routine follow-up. Her physician wants to adjust
her hypertension management plan and is considering 5. Which one of the following counseling points is best to
the most current hypertension guidelines. The physician share with Y.G.?
asks for your insight regarding the differences between A. Increase walking to 40 minutes each day.
the 2017 American College of Cardiology/American Heart B. Decrease alcohol to three beers per day.
Association (ACC/AHA) and the 2023 European Society C. Increase potassium to 7000 mg daily.
of Hypertension (ESH) hypertension guidelines. Which D. Decrease daily sodium intake by 1000 mg.
one of the following is the best education point to share
6. Which one of the following is best to recommend initiat-
with this colleague regarding the distinctions between
ing for Y.G.?
the 2017 ACC/AHA hypertension guidelines and the 2023
ESH hypertension guidelines? A. Ramipril and losartan
B. Enalapril and chlorthalidone
A. 2023 ESH guidelines have a more condensed
C. Verapamil and metoprolol
category of hypertension.
D. Amlodipine and diltiazem
B. 2017 ACC/AHA guidelines have a lower target blood
pressure goal for patients younger than 65.

PSAP 2025 Book 1 • Cardiology 23 Hypertension

7. A 36-year-old Hispanic woman has had persistently ele- C. Reduce lisinopril to 10 mg once daily and initiate
vated blood pressure despite lifestyle interventions for indapamide 2.5 mg once daily.
the past several months. Four weeks ago, her provider D. Reduce lisinopril to 10 mg once daily and initiate
decided to initiate lisinopril 10 mg once daily. Today, the sodium polystyrene sulfonate.
patient comes to clinic for a follow-up. Her blood pres-
10. A 55-year-old woman comes to her primary care pro-
sure is 138/84 mm Hg, with SCr 1.0 mg/dL (baseline
vider’s office for evaluation of hypertension. She has
SCr 0.8 mg/dL) and K 5.1 mg/dL (baseline K 4.8 mg/dL).
a history of hypertension for the past 5 years and has
Which one of the following is best to recommend for this
been taking amlodipine 5 mg once daily and hydrochlo-
patient’s hypertension management?
rothiazide 25 mg once daily, both in the morning. She
A. Continue lisinopril and add chlorthalidone because recently underwent ambulatory blood pressure monitor-
of hypokalemic effect and CV benefit. ing (ABPM), which revealed an average daytime SBP of
B. Continue lisinopril and add spironolactone because 130 mm Hg and average nighttime SBP of 135 mm Hg.
of hypokalemic effect and CV benefit. She has no other contributory medical history. At the
C. Discontinue lisinopril because of acute increase clinic, her blood pressure is 138/84 mm Hg and pulse rate
in potassium and serum creatinine, and initiate is 76 beats/min. Which one of the following is best to rec-
amlodipine instead. ommend for this patient’s hypertension management?
D. Discontinue lisinopril because of acute increase
A. Increase amlodipine to 10 mg once daily and move
in potassium and serum creatinine, and initiate
administration to the evening.
losartan instead.
B. Increase amlodipine to 10 mg once daily and keep
8. A 55-year-old woman is being seen for a blood pressure administration in the morning.
follow-up. Her blood pressure at last month’s visit was C. Change hydrochlorothiazide to chlorthalidone 25 mg
144/83 mm Hg; today, her blood pressure is 135/78 mm once daily and move administration to the evening.
Hg. Her medical history includes hypertension, asthma, D. Change hydrochlorothiazide to chlorthalidone 25 mg
hypothyroidism, and chronic kidney disease (CKD) (base- once daily and keep administration in the morning.
line SCr 1.8 mg/dL). She currently takes lisinopril 10 mg
11. A 48-year-old man comes to the primary care clinic for
once daily and amlodipine 5 mg once daily. Her labora-
evaluation of his hypertension, diagnosed 6 months ago.
tory values today are within normal limits, except for SCr
His medical history includes elevated blood pressure
1.9 mg/dL, urine albumin-to-creatinine ratio 309 mg/g,
readings over the past year, ranging from 132-136/79-
and estimated glomerular filtration rate (eGFR) 31 mL/
83 mm Hg. He has no contributory medical history and
min/1.73 m2. The patient denies any lower extremity
is not taking any medications. He leads an active life-
edema. Which one of the following is best to recommend
style, exercises regularly, and follows the DASH (Dietary
for this patient’s hypertension management?
Approaches to Stop Hypertension) diet, which he started
A. Increase lisinopril to 20 mg once daily. upon hypertension diagnosis. He has never smoked.
B. Increase amlodipine to 10 mg once daily. The patient has a family history of premature CV dis-
C. Initiate furosemide 40 mg once daily. ease (CVD) (father died of a myocardial infarction [MI] at
D. Initiate finerenone 10 mg once daily. age 58). His 10-year atherosclerotic CVD (ASCVD) risk
score is 5.1%. On examination today, his blood pressure
9. A 70-year-old man comes to the ED to report weak-
is 139/88 mm Hg and pulse rate is 72 beats/min. Physical
ness and malaise over the past week. His medical his-
examination is otherwise unremarkable. Which one of the
tory includes hypertension, for which he takes lisinopril
following is best to recommend for this patient’s hyper-
20 mg once daily. He also has a history of T2D, which
tension management?
is well controlled with metformin. On examination, the
patient appears fatigued, and his blood pressure is ele- A. Initiate nebivolol 5 mg once daily and reassess blood
vated at 155/82 mm Hg. Laboratory test results show K pressure in 1 month.
5.6 mEq/L, SCr 2.1 mg/dL (baseline 1.4 mg/dL), and urine B. Initiate irbesartan 150 mg once daily and reassess
albumin-to-creatinine ratio 32 mg/g. He reports adher- blood pressure in 1 month.
ence to his medications and no recent changes to his life- C. Initiate amlodipine/benazepril 2.5 to 10 mg once
style modifications. Which one of the following is best to daily and reassess blood pressure in 1 month.
recommend for this patient’s hypertension management? D. Continue with lifestyle modifications and reassess in
3 months.
A. Discontinue lisinopril and initiate amlodipine 5 mg
once daily.
B. Discontinue lisinopril and reduce potassium intake
to less than 3 g/day.

PSAP 2025 Book 1 • Cardiology 24 Hypertension

The next two questions pertain to the following case. The next two questions pertain to the following case.

R.M. is a 58-year-old man with a 10-year history of hyperten- R.J. is a 55-year-old woman with a history of T2D, hyperten-
sion. He comes to the ED after obtaining blood pressure read- sion (15 years), chronic coronary disease, and arthritis. She
ings of 180 to 190/120 to 130 mm Hg at home. He reports he comes to her primary care physician’s office for a follow-up
feels fine otherwise. R.M.’s blood pressure in the ED is 188/128 on her blood pressure, which she reports has been increasing
mm Hg. His other vital signs and laboratory measurements over the past 3 months. Two months ago, her home blood pres-
are normal. He reports that he has been prescribed lisinopril, sure readings ranged 129-133/75-79 mm Hg, but in the past
hydrochlorothiazide, and amlodipine, but he has been on a 2 weeks, they have ranged 138-142/80-84 mm Hg. You con-
2-week cross-country vacation and forgot to bring his medi- firm with her that she has taken her blood pressure correctly.
cations with him. He plans to fly back home in 4 days. R.M. R.J. has been taking lisinopril 40 mg once daily, amlodipine
reports that his blood pressure is normally around 130/80 mm 10 mg once daily, indapamide 5 mg once daily, and metop-
Hg when he is at home. rolol succinate 25 mg once daily. She reports adherence to
her medications and denies any significant changes in her
12. Which one of the following best assesses R.M.’s blood
diet or lifestyle. R.J. does not smoke and follows a balanced
pressure?
diet but admits occasional lapses in exercise because of knee
A. Refractory hypertension arthritis. She reports taking OTC acetaminophen occasionally
B. Resistant hypertension when her arthritis flares up. On examination, her blood pres-
C. Hypertensive urgency sure is 148/85 mm Hg (using standardized office blood pres-
D. Hypertensive emergency sure measurement) and pulse rate is 57 beats/min. Physical
13. Which one of the following is best to recommend for examination is unremarkable otherwise.
R.M.? 14. Which one of the following best assesses R.J.’s blood
A. Administer labetalol in the ED with a goal of pressure?
decreasing SBP to less than 140 mm Hg in the first A. Masked hypertension
hour. B. Resistant hypertension
B. Admit him to the hospital and administer nicardipine C. Pseudo-resistant hypertension
with a goal of decreasing SBP to less than 120 mm D. Refractory hypertension
Hg in the first hour.
15. Which one of the following is best to recommend for
C. Order a 1-week supply of his chronic
R.J.’s uncontrolled blood pressure?
antihypertensives to be filled at the hospital
pharmacy now and have him follow up with his A. Initiate spironolactone 25 mg once daily.
primary care provider next week. B. Change indapamide to chlorthalidone 25 mg once
D. Administer no medications in the ED and instruct daily.
him to return home immediately to restart his home C. Increase dose of metoprolol succinate to 50 mg once
drugs. daily.
D. Refer to hypertension specialist for further
evaluation.

PSAP 2025 Book 1 • Cardiology 25 Hypertension