Pharmacotherapy in Primary Care

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Primary Care

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broaden our knowledge, changes in treatment and drug therapy are required. The authors and the publisher of this work have checked with sources believed to be reliable in their efforts to provide information that is complete and generally in accord with the standards accepted at the time of publication. However, in view of the possibility of human error or changes in medical sciences, neither the authors nor the publisher nor any other party who has been involved in the preparation or publication of this work warrants that the information contained herein is in every respect accurate or complete, and they disclaim all responsibility for any errors or omissions or for the results obtained from use of the information contained in this work. Readers are encouraged to confirm the information contained herein with other sources. For example and in particular, readers are advised to check the product information sheet included in the package of each drug they plan to administer to be certain that the information contained in this work is accurate and that changes have not been made in the recommended dose or in the contraindications for administration. This recommendation is of particular importance in connection with new or infrequently used drugs.

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Primary Care

William D. Linn, PharmD

Associate Professor Feik School of Pharmacy University of the Incarnate Word San Antonio, Texas

Marion R. Wofford, MD, MPH

Professor of Medicine

Director of General Internal Medicine Hypertension Division

University of Mississippi Medical Center Jackson, Mississippi

Mary Elizabeth O’Keefe, MD

Geisinger Medical Center Danville, Pennsylvania

L. Michael Posey, BPharm

American Pharmacists Association Washington, D.C.

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DOI: 10.1036/0071456120

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Contributors ix

Foreword xv

Preface xvii

Introduction xix

PART 1. CARDIOVASCULAR DISORDERS 1

1. Hypertension 3

Deborah L. Cardell, Sarah Lapey, and Michelle V. Conde

2. Heart Failure 19

Tera D. Moore and Joe R. Anderson

3. Diagnosis and Management of Chronic

Coronary Heart Disease 37

Robert A. O’Rourke

4. Arrhythmias 67

Mark C. Granberry, William D. Linn, and Robert Chilton

5. Hypertrophic Cardiomyopathy 85 William D. Linn and Robert A. O’Rourke

6. Dyslipidemia 91

Leigh Ann Ross, Brendan Sean Ross, and Honey East

7. Peripheral Arterial Disease 103 Barbara Jean Hoeben

PART 2. RESPIRATORY DISORDERS 113

8. Asthma Management 115

Michelle S. Harkins and H. William Kelly

9. Management of Chronic Obstructive

Pulmonary Disease 125

Patrick F. Walsh and Michael L. Ayers

PART 3. GASTROINTESTINAL DISORDERS 133 10. Gastroesophageal Reflux Disease 135

Dianne B. Williams and Robert R. Schade

11. Peptic Ulcer Disease 143

Alexandria A. Dunleavy and Dalia Mack

12. Inflammatory Bowel Disease 151 Alexandria A. Dunleavy

13. Nausea and Vomiting 161

Rebecca E. Greene and Trevor McKibbin

14. Constipation and Diarrhea 169 Nicole L. McMaster-Baxter and

Sharon A. Jung Tschirhart

Clinical Associate Professor, University of Houston College of Pharmacy, Adjunct Clinical Assistant Professor of Medicine, Department of Infectious Diseases, Infection Control and Employee Health, UT-MD Anderson Cancer Center, Houston, Texas Chapter 44: Urinary Tract Infections and Prostatitis

Dana Dale, MD

Assistant Professor, Division of Endocrinology, University of Mississippi Medical Center, Jackson, Mississippi

Chapter 27: Thyroid Gland Disorders

Wendy S. Dean, PharmD

Clinical Pharmacist, HealthPark Medical Center Fort Myers, Florida

Chapter 28: Contraception

Leonard J. Deftos, MD, JD

Professor of Medicine, University of California, San Diego, Physician, San Diego VA Healthcare System, La Jolla, California Chapter 33: Osteoporosis

David N. Duddleston, MD

Clinical Assistant Professor, University of Mississippi Medical Center, Jackson, Mississippi

Chapter 39: Venous Thromboembolism

Alexandria A. Dunleavy, PharmD, BCPS

School of Pharmacy, Northeastern University , Bouve College of Health Sciences, Boston, Massachusetts

Chapter 11: Peptic Ulcer Disease Chapter 12: Inflammatory Bowel Disease

Honey East, MD

Associate Professor of Medicine, Department of Medicine, University of Mississippi Medical Center, Jackson, Mississippi

Chapter 6: Dyslipidemia

Kelly Echevarria, PharmD, BCPS

Clinical Assistant Professor, The University of Texas at Austin and the University of Texas Health Science Center at San Antonio, San Antonio, Texas

Chapter 41: Lower Respiratory Tract Infections

Mary Elizabeth Elliott, PharmD, Phd, RPh

Associate Profesor, University of Wisconsin School of Pharmacy, Clinical Pharmacist, Wm. S. Middleton VA Medical Center, Madison, Wisconsin

Chapter 35: Osteoarthritis

Michael E. Ernst, PharmD

Associate Professor, Division of Clinical and Administrative Pharmacy, College of Pharmacy and Department of Family Medicine, Roy J. and Lucille A. Carver College of Medicine, The University of Iowa, Iowa City, Iowa

Chapter 36: Gout

Susan C. Fagan, PharmD, BCPS

Professor of Pharmacy, University of Georgia, Adjunct Professor of Neurology, Medical College of Georgia, Augusta, Georgia Chapter 16: Stroke/Transient Ischemic Attacks

Douglas N. Fish, PharmD

Professor, Department of Clinical Pharmacy, University of Colorado School of Pharmacy, Clinical Specialist in Infectious

Diseases/Critical Care, University of Colorado Hospital, Denver, Colorado

Chapter 42: Skin and Soft Tissue Infections

Mark C. Granberry, PharmD

Associate Dean, Feik School of Pharmacy, University of the Incarnate Word, San Antonio, Texas

Rebecca E. Greene, Pharm D, BCOP

Clinical Assistant Professsor, University of Texas at Austin College of Pharmacy, Oncology Clinical Specialist, South Texas Veterans Health Care System, San Antonio, Texas

Chapter 13: Nausea and Vomiting

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R. Darryl Hamilton, MD

Assistant Professor, Division of Oncology, Department of Medicine, University of Mississippi Medical Center, Jackson, Mississippi Chapter 40: Anemia

Michelle S. Harkins, MD

Associate Professor of Medicine, Department of Internal Medicine, Division of Pulmonary and Critical Care, University of New Mexico, Albuquerque, New Mexico

Chapter 8: Asthma Management

T. Kristopher Harrell, PharmD

Assistant Professor of Pharmacy Practice, University of Mississippi School of Pharmacy, Jackson, Mississippi

Chapter 29: Menopausal Hormone Therapy

Barbara Jean Hoeben, Maj, USAF, PharmD, MSPharm, BCPS

Clinical Pharmacy Flight Commander, Wilford Hall Medical Center, Lackland AFB, Texas

Chapter 7: Peripheral Arterial Disease

Stephen S. Im, MD

Assistant Professor, University of Texas Health Science Center at San Antonio, South Texas Veterans Health Care System, Audie L.

Murphy Memorial Veterans Hospital, Division of Pulmonary and Critical Care Medicine, San Antonio, Texas

Chapter 23: Obstructive Sleep Apnea Hypopnea Syndrome

S. Rubina Inamdar, MD

Section Head, Division of Allergy and Immunology, Mercy Medical Group, Sacramento, California

Chapter 37: Allergic and Nonallergic Rhinitis Chapter 38: Otitis Media and Sinusitis

Dena Jackson, MD

Brookhaven Internal Medicine, Brookhaven, Mississippi Chapter 19: Headache Disorders

H. William Kelly, PharmD

Professor Emeritus of Pediatrics, Department of Pediatrics, University of New Mexico, Albuquerque, New Mexico Chapter 8: Asthma Management

Deborah S. King, PharmD

Associate Professor, Department of General Internal Medicine, University of Mississippi Medical Center, Jackson, Mississippi Chapter 19: Headache Disorders

Cynthia K. Kirkwood, PharmD, BCPP

Associate Professor of Pharmacy, Vice Chair for Education, Department of Pharmacy, Virginia Commonwealth University, Richmond, Virginia

Chapter 22: Anxiety Disorders

Sarah Lapey, MD

Clinical Assistant Professor of Medicine, University of Texas Health Science Center at San Antonio, Audie L. Murphy Division/South Texas Veterans Health Care System and Division of General Internal Medicine, San Antonio, Texas

Peter A. LeWitt, MD

Professor of Neurology, Wayne State University School of Medicine, Detroit, Michigan, Editor-in-Chief, Clinical Neuropharmacology, Director, Division of Parkinson’s Disease and Movement Disorders, Henry Ford Health Systems, Franklin Pointe Medical Center, Southfield, Michigan

Chapter 17: Parkinson Disease

Cara Liday, PharmD, CDE

Associate Professor, Department of Pharmacy Practice and Administrative Sciences, College of Pharmacy, Idaho State University, Pocatello, Idaho

Chapter 31: Benign Prostatic Hyperplasia

William D. Linn, PharmD

Associate Professor, Feik School of Pharmacy, University of the Incarnate Word, San Antonio, Texas

Chapter 5: Hypertrophic Cardiomyopathy

Sunny A. Linnebur, PharmD, FASCP, BCPS, CGP

Assistant Professor, Department of Clinical Pharmacy, University of Colorado Denver, Denver, Colorado

Chapter 30: Erectile Dysfunction

Annette K. Low, MD

Associate Professor of Medicine, University of Mississippi Medical Center, Jackson, Mississippi

Chapter 29: Menopausal Hormone Therapy

Dalia Mack, PharmD, AE-C, CDE

School of Pharmacy, Northeastern University, Bouve College of Health Sciences, Boston, Massachusetts

Chapter 11: Peptic Ulcer Disease

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Cynthia A. Mascarenas, PharmD, MSPharm, BCPP

Clinical Assistant Professor, College of Pharmacy, The University of Texas at Austin, Clinical Assistant Professor, Department of Pharmacology, The University of Texas Health Science Center at San Antonio, San Antonio, Texas

Chapter 21: Depression

Robb McIlvried, MD, MPH

Associate, Department of General Internal Medicine Geisinger Medical Center, Danville, Pennsylvania Chapter 20: Pharmacotherapy for Alzheimer Disease

Trevor McKibbin, PharmD

Advanced Practice Masters Student, University of Texas at Austin College of Pharmacy, Oncology Pharmacy Resident, South Texas Veterans Health Care System, San Antonio, Texas

Chapter 13: Nausea and Vomiting

Nicole L. McMaster-Baxter, PharmD, MS, BCPS

Michael E. DeBakey VA Medical Center–Houston, The University of Texas at Austin College of Pharmacy, Houston, Texas

Chapter 14: Constipation and Diarrhea

Shyamal Mehta, MD, PhD

Resident in Neurology, Department of Neurology, Medical College of Georgia, Augusta, Georgia

Chapter 16: Stroke/Transient Ischemic Attacks

Deborah S. Minor, PharmD

Associate Professor of Medicine, University of Mississippi Medical Center, Jackson, Mississippi

Chapter 19: Headache Disorders

Tera D. Moore, PharmD, BCPS

Primary Care Clinical Pharmacy Specialist, South Texas Veterans Health Care System, Clinical Assistant Professor, The University of Texas at Austin College of Pharmacy, San Antonio, Texas Chapter 2: Heart Failure

Troy A. Moore, PharmD, MSPharm, BCPP Assistant Professor, Department of Psychiatry, Division of Schizophrenia and Related Disorders, The University of Texas Health Science Center at San Antonio, San Antonio, Texas Chapter 21: Depression

Candis M. Morello, PharmD, CDE, FCSHP

Assistant Professor of Clinical Pharmacy, Ambulatory Care Pharmacist Specialist, Skaggs School of Pharmacy and

Pharmaceutical Sciences, University of California, San Diego, La Jolla, California

Chapter 33: Osteoporosis

Laura A. Morgan, PharmD, BCPS

Assistant Professor of Pharmacy, Department of Pharmacy, Virginia Commonwealth University, Richmond, Virginia

Chapter 22: Anxiety Disorders

Nicole Murdock, PharmD, BCPS

Pocatello Family Medicine, Idaho State University, Pocatello, Idaho Chapter 31: Benign Prostatic Hyperplasia

Rocsanna Namdar, PharmD

Assistant Professor, College of Pharmacy, University of New Mexico, Albuquerque, New Mexico

Chapter 43: Tuberculosis

Beverly D. Nixon-Lewis, DO

Assistant Professor, Department of Family and Community Medicine, Texas Tech University Health Sciences Center, Amarillo, Texas

Chapter 32: Urinary Incontinence

Robert A. O’Rourke, MD

Charles Conrad Brown Distinguished Professor in Cardiovascular Disease, Department of Medicine/Cardiology, The University of Texas Health Science Center at San Antonio, San Antonio, Texas Chapter 3: Diagnosis and Management of Chronic Coronary Heart Disease

Chapter 5: Hypertrophic Cardiomyopathy

Charles A. Peloquin, PharmD

Director, Infectious Disease, Pharmacokinetics Laboratory, National Jewish Medical and Research Center, Denver, Colorado

Chapter 43: Tuberculosis

Randall A. Prince, PharmD, FCCP

Professor and Director, University of Houston Anti-infective Research Laboratories, Adjunct Professor of Medicine, Department of Infectious Diseases, Infection Control and Employee Health, UT-MD Anderson Cancer Center, Houston, Texas

Chapter 44: Urinary Tract Infections and Prostatitis

Susan J. Rogers, BS, PharmD, BCPS

Clinical Pharmacy Specialist, Audie L. Murphy Memorial Veterans Hospital, Assistant Clinical Professor of Pharmacology, The University of Texas Health Science Center at San Antonio, San Antonio, Texas

Chapter 15: Epilepsy

Brendan Sean Ross, MD

Clinical Associate Professor, Department of Pharmacy Practice, University of Mississippi School of Pharmacy, Staff Physician, G.V.

(Sonny) Montgomery Veterans Affairs of Medical Center, Jackson, Mississippi

Chapter 6: Dyslipedemia

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Leigh Ann Ross, PharmD, BCPS, CDE

Associate Professor and Chair, Department of Pharmacy Practice, University of Mississippi School of Pharmacy, Jackson, Mississippi Chapter 6: Dyslipidemia

Rebecca A. Rottman, PharmD, BCPS, CGP

Geriatrics Clinical Pharmacy Specialist, South Texas Veterans Health Care System, Clinical Assistant Professor, University of Texas College of Pharmacy at Austin, University of Texas Health Science Center at San Antonio (UTHSCSA), San Antonio, Texas Chapter 39: Venous Thromboembolism

Laurajo Ryan, PharmD, MSc, BCPS, CDE

Clinical Assistant Professor, University of Texas at Austin College of Pharmacy, University of Texas Health Science Center at San Antonio, San Antonio, Texas

Chapter 45: Sexually Transmitted Diseases

Kathryn Sabol, PharmD, BCPS

Infectious Diseases Clinical Pharmacy Specialist, Parkland Health and Hospital System, San Antonio, Texas

Chapter 41: Lower Respiratory Tract Infections

Robert R. Schade, MD

Professor, Department of Medicine, Chief, Section of Gastroenterology and Hepatology, Medical College of Georgia, Augusta, Georgia Chapter 10: Gastroesophageal Reflux Disease

Arthur A. Schuna, MS, FASHP

Rheumatology Pharmacotherapist, William S. Middleton VA Medical Center, Clinical Professor, University of Wisconsin School of Pharmacy, Madison, Wisconsin

Chapter 34: Rheumatoid Arthritis

Jinna Shepherd, MD

Associate Professor, Division of General Internal

Medicine/Hypertension, Department of Medicine, University of Mississippi Medical Center, Jackson, Mississippi

Chapter 40: Anemia

Renu F. Singh, PharmD

Assistant Clinical Professor, Ambulatory Care Pharmacist Specialist, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, California Chapter 33: Osteoporosis

Ronald Solbing, MD

Idaho State University Family Medicine Residency,, Pocatello, Idaho Chapter 31: Benign Prostatic Hyperplasia

Jimmy L. Stewart, MD

Associate Professor of Medicine and Pediatrics, Program Director, Combined Internal Medicine/Pediatrics Residency Program, University of Mississippi Medical Center, Jackson, Mississippi Chapter 26: Metabolic Syndrome

Scott Strassels, PharmD, PhD, BCPS

Assistant Professor, Division of Pharmacy Practice, University of Texas at Austin, Austin, Texas

Chapter 18: Persistent Pain

Caryl Sumrall, FNP

Clinical Instructor, University of Mississippi Medical Center, Jackson, Mississippi

Chapter 25: Diabetes Mellitus Management

Sharon A. Jung Tschirhart, PharmD, BCPS

South Texas Veterans Healthcare System, Audie L. Murphy Division, The University of Texas at Austin College of Pharmacy, Houston, Texas

Chapter 14: Constipation and Diarrhea

Jeffrey I. Wallace, MD, MPH

Associate Professor, Department of Medicine, University of Colorado at Denver and Health Sciences Center, Denver, Colorado

Chapter 30: Erectile Dysfunction

Patrick F. Walsh, DO

Associate, Critical Care Medicine, Geisinger Medical Center, Danville, Pennsylvania

Chapter 9: Management of Chronic Obstructive Pulmonary Disease

Dianne B. Williams, PharmD, BCPS

Drug Information and Formulary Coordinator, Medical College of Georgia Health System, Clinical Associate Professor, University of Georgia College of Pharmacy, Augusta, Georgia

Chapter 10: Gastroesophageal Reflux Disease

Marion R. Wofford, MD, MPH

Professor of Medicine, Director of General Internal Medicine, Hypertension Division, University of Mississippi Medical Center, Jackson, Mississippi

Chapter 26: Metabolic Syndrome

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harmacotherapy in Primary Care is a book chock full of useful, easily accessible information and advice. Busy practitioners seeking quick overviews and practical management recommendations for many conditions seen in primary care will be pleased with its format and content. Well-laid out chapters focus on the following:

Clinical Presentation, Physical Findings, Diagnostic Evaluation, and Management. Management sections comprehensively address asymptomatic and sympto- matic patients, referral and consultation questions, integration of pharmacotherapy with nonpharmaco- logic treatment, and long-term monitoring. Particularly attractive for busy readers are the multiple tables and

concise algorithms of treatment strategies, and the clearly written thumbnail summaries of key points.

Unquestionably, the authors have achieved their high aim of presenting a well-reasoned and streamlined approach to therapeutic decision-making about common primary care disorders.

Cynthia Mulrow MD, MSc, MACP Deputy Editor, Annals of Internal Medicine Clinical Professor of Medicine University of Texas Health Science Center at San Antonio

San Antonio, Texas

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linicians are in constant need of information. It is estimated that providers need answers to two questions for every three patients seen. Unfortunately, many decisions appear to be opinion based, highly variable, and without clear justification. The difference between an outstanding clinician and an average one is the ability to quickly find high-quality evidence generalizable to their patients.

The authors of Pharmacotherapy in Primary Care have been carefully chosen and their clinical experience represents tens of thousands of patient visits. Their author- itative recommendations provide evidence-based information that is essential to accurate clinical decision making. This text will be a valuable resource for pri- mary care providers of all disciplines. Pharmacotherapy in Primary Care is not intended to be an encyclopedic textbook. For in-depth reviews, readers should refer to texts such as Pharmacotherapy: A Pathophysiologic Approach, Harrison’s Principles of Internal Medicine, or The Heart.

Pharmacotherapy in Primary Care includes the search strategy used by the authors, to allow the reader to know when the information was assessed, and to feel confi- dent that the most relevant material is included. There are numerous tables, algorithms, and flow diagrams to facilitate finding key information. The authors include insights regarding the need for subspecialty referral or hospitalization, and each chapter closes with an evi- dence-based summary. Pharmacotherapy in Primary Care is structured so that clinicians can quickly find answers to specific questions. Readers will feel that they have consulted with a specialist after reading a chapter.

In closing, we would like to thank Karen Davis and her colleagues at McGraw-Hill for their support to Pharmacotherapy in Primary Care. Without their resources, dedication, and faith in us, this first edition would not have been possible.

The Editors July 2008

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linicians are constantly faced with choices about how to accurately achieve a diagnosis, estimate a prog- nosis, choose an optimal treatment strategy, or assess the possibility of harm, in order to provide the best care to their patients. Increasingly, clinicians are turning to the principles of evidence-based medicine (EBM) to help them make these decisions. This text, Pharma- cotherapy in Primary Care, seeks to translate the best avail- able evidence for the most common diseases encoun- tered daily in physician offices, ambulatory care clinics, hospitals, and pharmacies.

The practice of EBM means to (1) recognize informa- tional need while caring for a patient, (2) identify the best existing evidence to help resolve the problem, (3) consider the evidence in light of the actual circumstances, and (4) integrate the evidence into a medical plan.

Medical information is growing incessantly—-the number of citations more than doubled in the past decade. Each year, 10,000 randomized controlled trials addressing the impact of health care interventions are published. The information synthesized by the authors of this book provide a sound outline on how to care for the majority of patients clinicians see, but when pre- sented with a patient whose clinical characteristics dif- fer in important ways, care must be individualized. How can busy frontline clinicians sort the good from the bad and identify the best evidence to resolve their problem at the time of such patient visits?

FOCUS THE SEARCH

The search for evidence begins with identifying relevant articles in the peer-reviewed literature. To expedite and

target a literature search, the clinician must phrase the problem in a clear, precise, and specific question. The acronym PICO can be helpful to clarify the question and search strategy¹:

P patient (including the disease, comorbidities, age, and other relevant characteristics)

I intervention (drug therapy, diagnostic test, exposure, and other possible treatments) C comparison (of possible actions and interven-

tions with other drugs, tests, procedures) O outcome (cure, disease avoidance, accurate

diagnoses, and other clinical, humanistic, and economic measures of success or failure)

BE MORE CRITICAL

The authors of each chapter in Pharmacotherapy in Pri- mary Care have carefully searched and critically appraised for the best available evidence to provide their recommendations for patients with 45 common diseases listed in the Table of Contents. Asking an expert or a colleague may be the quickest way to get advice on how to proceed with these patients, but be cautious, as these people may be just as overwhelmed by the volume and complexity of medical information as you are or their advice may be out of date. Searching PubMed or MEDLINE may simply be too labor inten- sive for point-of-care decisions.

In such cases, consider evidence-based resources that have conducted the search, filtered the high

1Ghosh AK, Ghosh K. Enhance your practice with evidence-based medi- cine. Patient Care. February 2000:32–56.

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quality, relevant evidence, and summarized the results for the busy clinician. Reputable evidence-based data- bases—including the Cochrane Library, Up-to-Date, National Guideline Clearinghouse, and PIER (Physi- cians’ Information and Education Resource from the American College of Physicians)—provide evidence- based discussions of hundreds of specific clinical situ- ations. For example, the Cochrane Collaboration, available online at www.cochrane.org, listed the following top 10 accessed reviews when this foreword was written in September 2007:

• Membrane sweeping for induction of labor

• Vitamin C for preventing and treating the common cold

• Ear drops for the removal of ear wax

• Low glycemic index or low glycemic load diets for overweight and obesity

• Glucosamine therapy for treating osteoarthritis

• Surgery for thumb (trapeziometacarpal joint) osteoarthritis

• Surgery for degenerative lumbar spondylosis

• Effects of low sodium diet versus high sodium diet on blood pressure, renin, aldosterone, catecholamines, cholesterols, and triglyceride

• Diacerein for osteoarthritis

• Hypotonic versus isotonic saline solutions for intra- venous fluid management of acute infections Accessing these resources is like having your own personal librarian to conduct searches and an on-staff group of world-renowned experts to assess the literature for you.

INTEGRATE INTO PRACTICE

Integrating evidence into practice requires combining the best evidence with knowledge of disease and patient management. The usefulness of an intervention depends not only on its efficacy but also on whether the magnitude of the benefit outweighs the risks, costs, benefits of existing alternative and whether the intervention is realistic and acceptable considering the patient’s values and health care delivery context.

The needed skills for practicing EBM may appear daunting, but once acquired, they can help the health professionals to better use available resources and time by knowing how to focus a search and be more critical of what research studies and information to integrate in their knowledge base.

Pharmacotherapy in Primary Care fulfills the four attrib- utes to make it useful in daily clinical practice: it is relevant to everyday practice, evidence-based, concise, and reader friendly. It is intended to be the first-line resource clinicians can turn to when faced with clinical management options. For more in-depth review and discussion of disease management, the reader may refer to textbooks such as Harrison’s Principles of Internal Med- icine or the Pharmacotherapy: A Pathophysiologic Approach on which this primary care resource was based.

Although the chapters in this textbook vary in their content, they use a similar outline to help the reader access quickly the information they need:

• Clinical presentation

• Physical findings

• Diagnostic evaluation

• Risk stratification

• Management

• Evidence-based summary

The chapters use flow charts, figures, and tables to sim- plify the description of investigations and treatments recommended for the various common conditions in primary care.

Pharmacotherapy in Primary Care will help frontline clinicians identify the array of potential decisions and provide them with the evidence that, when used in conjunction with the clinicians’ individual clinical judgment and their patients’ values and expectations, will assist greatly in the millions of patient-care decisions that must be made daily in primary care settings.

Elaine Chiquette, PharmD San Antonio, Texas L. Michael Posey, BPharm Athens, Georgia

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1

PART 1

Cardiovascular Disorders

C H A P T E R S

1 Hypertension 2 Heart Failure

3 Diagnosis and Management of Chronic Coronary Heart Disease

4 Arrhythmias

5 Hypertrophic Cardiomyopathy 6 Dyslipidemia

7 Peripheral Arterial Disease

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3

Hypertension

Deborah L. Cardell, Sarah Lapey, and Michelle V. Conde

SEARCH STRATEGY

A comprehensive search of the medical literature was per- formed in January 2008. The search, limited to human subjects and English language journals, included MED- LINE^®, PubMed, the Cochrane Database of Systematic Reviews, and UpToDate^®. The current Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VII) can be found at http://www.nhlbi.nih.gov/guidelines/

hypertension/

PREVALENCE AND DISEASE BURDEN

Hypertension (HTN) is both the most common rea- son for ofﬁce visits in the United States as well as the most common indication for prescription medicines.

Twenty-four percent of the adult population, or approximately 50 million people, have HTN.

Although 53% of hypertensive patients are receiving pharmacotherapy, only a disappointing 14% to 25%

of these patients succeed in meeting blood pressure (BP) treatment goals.¹Elevated BP is associated with a continuum of increasing risk for cardiovascular disease, stroke, and kidney disease. Each incremental rise in BP above 115/75 translates into an elevated risk of end-organ damage.²Reduction in BP decreases the risk of stroke by 35% to 40%, myocardial infarc- tion (MI) by 20% to 25%, and heart failure by greater than 50%.³The successful control of BP could therefore potentially reduce the deleterious effects of three of the most common medical conditions affecting Americans.

SCREENING

The treatment of HTN is impossible without an aware- ness of the diagnosis. National Health and Nutrition Examination Survey (NHANES) III found that only 70% of patients meeting diagnostic criteria for HTN were in fact cognizant of their condition. Currently, the U.S. Preventive Services Task Force recommends screening all adults more than 18 years of age annually for HTN (grade A recommendation).⁴

MEASUREMENT OF BP PROPER TECHNIQUE

The diagnosis of HTN requires accurate measurements of BP. The JNC VII includes recommendations for proper BP measurement based on expert guidelines.²First, an appropriate cuff size must be selected so as to avoid falsely elevated (from very small size) or falsely decreased (from very large size) BP readings.

The bladder, which is the rubber, inﬂatable portion of the cuff, should encircle at least 75% to 80% of the upper arm, and the width of the cuff should span at least 40% of the length of the upper arm.⁵Ideally, the patient should be seated in a chair for 5 minutes prior to the measurement of BP. Ingestion of caffeine, tobacco products, or medications potentially raising the BP should be avoided for 30 to 60 minutes prior to measuring the BP. Talking during BP measurement can falsely elevate the BP, as can excessively cold temperatures or improper patient positioning. The patient’s arm should be supported at the level of the heart, and the sphygmomanometer, within 3 feet of

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the examiner and preferably at the eye level. With its lower edge positioned 2 to 3 cm above the brachial artery, the cuff is then inflated to approximately 30 mm Hg higher than the point at which the brachial artery can no longer be palpated. This value is determined prior to the actual BP measurement by inflating the cuff while palpating the radial artery and noting the mm Hg at which the pulse disappears; this is the number above which the sphygmomanometer must be inflated. The stethoscope is then held lightly over the brachial artery while the cuff is slowly deflated at a rate of 2 to 3 mm Hg per heartbeat or per second. Deflat- ing the cuff any faster results in an underestimation of systolic and overestimation of diastolic pressures.⁵The diagnosis of HTN can be established when there are two to three elevated readings from separate office visits at least a week apart.

Although the mercury sphygmomanometer has been the “gold standard” for decades, its use is being phased out and replaced by aneroid and electronic devices, because of the environmental concerns of potential mercury leakage. Health care personnel must ensure that their BP equipment is kept in the best possible working order by regular inspection and valida- tion for accuracy. Tubing should be checked for leaks, hook and eye closures must be strong enough to remain fastened during inﬂation, and aneroid sphygmo- manometers must be calibrated at least every 6 months.

Over time, with repeated jostling and movement, aneroid devices become less and less accurate, causing an underestimation in the true BP.

HOME BP MONITORING

Home BP monitoring, or self-monitoring of BP by the patient outside of the clinic, represents an area of increased recent interest in the literature. An agreed- upon application includes the evaluation of patients with suspected white coat HTN.⁶ White-coat HTN is deﬁned as an elevated BP (140/90 mm Hg) in the clinic setting, with a concomitant normal BP reading (135/85 mm Hg) at home. As would be expected, further assessment of these patients fails to demonstrate evidence of end-organ damage.

The literature on ambulatory BP monitoring (ABPM) has uncovered a trend in which home BP readings are consistently lower than ofﬁce measurements.

Consequently, BP goals for home readings have been adjusted, with home BP 135/85 mm Hg corresponding to an ofﬁce BP goal of 140/90 mm Hg.⁷ The same factors affecting the accuracy of the ofﬁce-based BP measurement also impact home BP measurement, and home BP devices often do not perform as well in the community as compared with the laboratory set-

ting.⁸In light of the above barriers, home BP monitoring should be limited to certain special circumstances, including the assessment of response to therapy, efforts to improve patient compliance, and the evaluation of suspected white-coat HTN. Its use has not been univer- sally recommended for the regular care of all hypertensive patients.²

AMBULATORY BP MONITORING

ABPM refers to an outpatient-evaluation technique in which multiple-automated BP readings are obtained at specific intervals over the span of 24 to 72 hours. ABPM provides additional data that potentially provides insight into BP control during a patient’s everyday activities. Similar to home BP monitoring, there is a recent and growing interest in ABPM in the medical community and literature. Prospective studies have suggested that ambulatory BP data may more accurately reflect a patient’s BP and better correlate with target-organ injury (such as left ventricular hypertrophy) than office-based BP measurements;^9,10however, long-term outcomes are lacking. In general, the research assessing long-term outcomes on the use of clinic-based BP monitoring far exceeds the corresponding studies for ABPM. Therefore, in-office BP readings still remain the gold standard for decision-making in BP management. While admittedly the literature on ABPM is newer, there is a general consensus that there are select groups of patients, including those with suspected white-coat HTN, refractory HTN with apparent drug resistance, and patients in whom efficacy of their antihypertensive regimen is under evaluation, for whom ABPM may be beneficial. Medicare has recently approved reimbursement for ABPM in patients with suspected white-coat HTN.

Advocates for ABPM point to the money that is wasted on 20% to 25% of the hypertensive patients who have white-coat HTN and are unnecessarily treated with medications. Some experts, however, argue that patients with white-coat HTN are not completely free of cardiovascular risk and have a risk that is more than normotensive patients and yet less than that of patients with sustained HTN.^11,12Still other studies have found no increased risk for cardiovascular outcomes for patients determined to have only white-coat HTN.¹³ Patients determined to have white-coat HTN need close follow-up as the incidence of stroke rises after 6 years.⁷ A recent review article suggests that ABPM is best suited for more accurate assessment of risk in hypertensive patients, for evaluating nighttime BPs when clinically relevant and for evaluating the effectiveness of various antihypertensive drugs when they are being compared in clinical studies.¹⁴

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DEFINITION AND CLASSIFICATION OF BP

JNC VII introduced a new classiﬁcation of “pre-HTN,”

corresponding to a systolic BP (SBP) of 120 to 139 mm Hg and/or a diastolic blood pressure (DBP) of 80 to 89 mm Hg. This is not a disease category but rather a designation, aiming to identify individuals at high risk for the development of HTN. Prehypertensive patients are ideal targets for early intervention through lifestyle modifications, so as to prevent the progressive increase in BP leading to HTN. Clinicians can educate these patients regarding their risk and encourage them to make lifestyle modifications. Those patients with pre-HTN who also have underlying renal insuffi- ciency or diabetes, on the other hand, are candidates for pharmacotherapy, if their BP remains above 130/80, despite lifestyle modifications. In all other patients without compelling indications for treatment, a BP can be rechecked within 1 year (see Table 1-1).

INITIAL EVALUATION

The diagnosis of HTN requires two to three separate BP readings, higher than 140/90 mm Hg, at least a week apart. The initial approach in assessing a hypertensive patient consists of a global cardiovascular disease risk assessment, evaluation for the presence of end-organ damage, and a search for secondary causes of HTN, if indicated (Fig. 1-1 and Tables 1-2 and 1-5).

MANAGEMENT

LIFESTYLE MODIFICATIONS

Lifestyle modiﬁcations represent a crucial part of a mul- tidisciplinary BP management approach and offer the added beneﬁt of decreasing cardiovascular risk independent of BP changes. Health care providers should encourage all prehypertensive (SBP 120 to 139 mm Hg or DBP 80 to 89 mm Hg) and hypertensive (BP 140/

90 mm Hg) patients regarding the importance of weight reduction; dietary modiﬁcations, as exempliﬁed by the Dietary Approaches to Stop Hypertension (DASH)

Table 1-1. JNC VII Classiﬁcation of BP for Adults²

BP Classiﬁcation SBP (mm Hg) DBP (mm Hg) Follow-up (Without Compelling Indications for Treatment)

Normal 120 and 80 2 years

Pre-HTN 120–139 or 80–89 Recheck in 1 year

Stage 1 HTN 140–159 or 90–99 Conﬁrm within 2 months

Stage 2 HTN 160 or 100 180/110—Evaluate and treat within 1 month

180/110—Evaluate and treat immediately or within 1 week (depending upon the clinical situation) Source: Chobanian et al: Natl Hi BP. Hypertension 2003;42:1206

Figure 1-1. Selected physical examination findings. *Jugular venous distention: 85–100% probability of increased filling pressures⁶⁷; Abdominal bruit: sensitivity 39% and specificity 99% for a systolic-diastolic bruit for detecting true renal atherosclerotic disease.⁶⁸

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eating plan (diet rich in fruits, vegetables, and low-fat dairy products) and dietary sodium restriction, regular physical activity, and moderation of alcohol consumption. These lifestyle changes can lower BP, and also enhance the efﬁcacy of antihypertensive medications. The most effective nonpharmacological lifestyle modification is weight loss. The DASH diet, recom- mending four servings of fruit, four servings of vegetables, and three servings of low-fat dairy products per day, also has signiﬁcant BP lowering effects independent of weight loss. In some individuals, this dietary plan approaches the impact of a single antihypertensive medication.² Exercise recommendations consist of 30 minutes of brisk, aerobic activity most days of the week. Alcohol moderation refers to limiting intake to no more than two drinks for men and one drink for women each day (Table 1-3). Additionally, given that the overall goal is reduction in cardiovascular-related disease and not simply BP reduction, health care providers should also assist patients in tobacco cessation.

INITIAL PHARMACOLOGIC THERAPY

The JNC VII recommends initial drug therapy with a thiazide-type diuretic in the absence of a compelling indication for another antihypertensive drug class.² This recommendation supports the ﬁndings of The Antihypertensive and Lipid Lowering Treatment to Pre- vent Heart Attack Trial (ALLHAT), which prospectively randomized 42418 hypertensive patients with one addi-

tional risk factor for coronary artery disease to low-dose chlorthalidone or one of the following newer antihypertensive agents: lisinopril, amlodipine, and doxazosin.¹⁵ The doxazosin arm was terminated prematurely as a result of the increased incidence of heart failure relative to chlorthalidone. The primary outcomes were fatal coronary heart disease and nonfatal MI, and the inci- dences were similar across the chlorthalidone, amlodipine, and lisinopril groups, consistent with results from other trials.^16,17Additionally, the chlorthalidone group showed superiority in several secondary endpoints, including improved heart failure protection compared to both amlodipine and lisinopril and improved stroke protection compared with lisinopril.

The results of the ALLHAT trial have sparked contro- versy. First, open-label agents or “step-up agents” were used for additional BP control and included atenolol, reserpine, clonidine, and hydralazine, combinations which, in general, do not mirror clinical practice.

Approximately 40% of patients required these additional agents for BP control. Additionally, increased fasting glucose levels 126 mg/dL in nondiabetic patients assigned to chlorthalidone were noted. Although this change did not increase cardiovascular morbidity and mortality relative to the other groups during the mean follow-up of 4.9 years, experts raised the concern that signiﬁcant deleterious changes in cardiovascular morbidity and mortality might become apparent after 5 years.^18,19

The ALLHAT trial also found that lisinopril had higher rates of stroke, heart failure, and combined cardiovascular outcomes than chlorthalidone, which was a surprising ﬁnding given reports of improved cardiovascular outcomes with angiotensin converting enzyme (ACE) inhibitors independent of its BP lowering effects.²⁰Several authors highlight that the chlorthalidone arm achieved tighter BP control relative to the lisinopril arm, potentially accounting for the cardiovascular differences.^21–24

Table 1-2. Routine Laboratory Studies Hematocrit

Urinalysis Glucose Creatinine

Electrolytes Fasting lipid proﬁle Electrocardiogram

Table 1-3. JNC VII Lifestyle Modiﬁcation Recommendations²

Modiﬁcation Recommendation Average SBP Reduction Range (mm Hg)

Weight reduction Maintain normal BMI (18.5–24.9 kg/m²) 5–20 (per 10 kg)

DASH eating plan Eat a diet rich in fruits, vegetables, and 8–14

low-fat dairy products with reduced content of saturated and total fat.

Dietary sodium reduction Reduce dietary sodium intake to 100 mmol/d 2–8 (2.4 g sodium or 6 g sodium chloride).

Aerobic physical activity Regular aerobic physical activity at 4–9 least 30 min/d, most days of the week.

Moderation of alcohol consumption Men: Limit to 2 drinks/d; 2–4 women: Limit to 1 drink/d;

1 drink ⬃12 oz beer, 5 oz wine, or 1.5 oz 80-proof whiskey.

Source: Chobanian et al: Natl Hi BP. Hypertension 2003;42:1206

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The Anglo-Scandinavian Cardiac Outcomes Trial:

Blood Pressure Lowering Arm (ASCOT-BPLA), which prospectively randomized 19 257 hypertensive patients, mean age of 63 years with three cardiovascular risk factors, to an amlodipine-based strategy or an atenolol- based strategy, has added another layer of complexity.²⁵ This trial found that an antihypertensive strategy based on amlodipine, with perindopril (an ACE inhibitor) added as required, reduced all-cause mortality, fatal and nonfatal stroke, and total cardiovascular events and procedures compared to an atenolol-based strategy, with bendroﬂumethiazide added as required. The trial was prematurely terminated after 5.5 years median follow- up because of an 11% risk reduction in all-cause mortality in the amlodipine/perindopril group compared with the atenolol/bendroﬂumethiazide group. The majority of patients (78%) were taking at least two antihypertensive agents by the end of the trial.

The results of the ALLHAT and ASCOT trials are seemingly contradictory. One explanation is that atenolol may not be a suitable ﬁrst-line antihypertensive drug compared to other classes. A systematic review found no difference in cardiovascular morbidity and mortality in patients with primary HTN between placebo and atenolol, despite a lower BP achieved with atenolol relative to placebo.²⁶When compared to other antihypertensive agents (thiazide diuretics, calcium- channel antagonists, ACE inhibitors, angiotensin II receptor blockers [ARBs]), mortality was higher with atenolol than with other agents (relative risk [RR] 1.13;

95% confidence interval [CI] 1.02–1.25). Other studies have also questioned the efficacy of -blockers as first- line drug agents for HTN in the older adults.^27,28poten- tially accounting for the differences in the two treatment arms of the ASCOT trial. A meta-analysis evaluated 13 randomized controlled trials comparing treatment with different -blockers (not limited to atenolol) with other antihypertensive classes. The meta-analysis concluded that -blocker treatment was associated with a 16%

higher RR of stroke (95% CI 4–30%; p 0.009) compared with other classes.²⁹ Thus, the results of the ASCOT trial do not negate ALLHAT’s ﬁnding that thiazide diuretics are useful ﬁrst-line antihypertensive drugs in patients with uncomplicated HTN.

A systematic review by the Blood Pressure Lowering Treatment Trialists’ Collaboration evaluated the effects of different antihypertensive regimens on reducing major cardiovascular events and concluded that ACE inhibitors, calcium-channel blockers, and diuretics and/or -blocker-based regimens similarly reduced the risk of total major cardiovascular events.³⁰BP lowering itself reduced the risk of total major cardiovascular events regardless of the speciﬁc regimen used. In fact, the strongest determinant in reducing total major car-

diovascular events was the level of BP achieved. There were differences in speciﬁc outcomes, most notably heart failure prevention: ACE inhibitors and diuretics and/or -blocker-based regimens were associated with a decreased risk of heart failure compared with calcium- channel blocker regimens. This review, which included the ALLHAT trial but not the ASCOT trial, did not separate diuretic treatment from -blocker treatment results and combined studies with diuretics and/or

-blockers into one category.

In summary, evidence still remains that thiazide diuretics are effective as first-line agents in the treatment of uncomplicated HTN. Despite chlorthalidone’s use as the thiazide-like diuretic evaluated in most studies, hydrochlorothiazide, which is widely available in the United States, can also be considered as a rational diuretic choice.³¹ ACE-inhibitor therapy and calcium- channel blockers are also reasonable antihypertensive drug agents. -Blockers are less efficacious as a first-line agent for HTN in the older adults; however, they remain strongly indicated in patients with chronic con- gestive heart failure, asymptomatic left ventricular dysfunction, a history of MI or angina.^32,33Numerous trials show that a significant number of patients will require at least two drugs to achieve adequate BP control. ARBs are also promising antihypertensive agents and, compared with atenolol, are associated with a significant reduction in cardiovascular morbidity and mortality in hypertensive patients with ECG evidence of left ventricular hypertrophy.³⁴ARBs are particularly indicated in patients who develop cough with an ACE inhibitor.

SPECIAL POPULATIONS African Americans

Non-Hispanic black ethnicity is independently associated with increased rates of HTN.¹Furthermore, in addition to the increased likelihood of developing HTN, African American patients with HTN have the highest morbidity and mortality from HTN of any population group in the United States.³⁵The reasons for the higher associated morbidity and mortality are mul- tifactorial and require further elucidation. Contribut- ing factors, as cited by the Hypertension in African Americans Working Group of the International Society on Hypertension in Blacks, include medical providers’

nonaggressive and inconsistent efforts in diagnosing and treating HTN.³⁶Additionally, African Americans consume less potassium than white Americans and this dietary characteristic may also be a contributing factor.

Drugs that inhibit the renin system, including ACE inhibitors, ARBs, and -blockers, reportedly have a decreased BP lowering effect as compared with thiazide

Pharmacotherapy in Primary Care

Primary Care

Primary Care

William D. Linn, PharmD

Marion R. Wofford, MD, MPH

Mary Elizabeth O’Keefe, MD

L. Michael Posey, BPharm

CONTENTS

P

C

C

PART 1

Cardiovascular Disorders

Hypertension

Deborah L. Cardell, Sarah Lapey, and Michelle V. Conde