This Article  • References  • Full text PDF  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Contact me when this article is cited  Related Content  • Similar articles in JAMA  Social Bookmarking   What's this?

A Systematic Review and Meta-analysis

Bruce M. Psaty, MD, PhD; Nicholas L. Smith, MPH; David S. Siscovick, MD, MPH; Thomas D. Koepsell, MD, MPH; Noel S. Weiss, MD, DrPH; Susan R. Heckbert, MD, PhD; Rozenn N. Lemaitre, PhD, MPH; Edward H. Wagner, MD, MPH; Curt D. Furberg, MD, PhD

JAMA. 1997;277(9):739-745.

Abstract
Objective.
—To review the scientific evidence concerning the safety and efficacy of various antihypertensive therapies used as first-line agents and evaluated in terms of major disease end points.

Data Sources.
—MEDLINE searches and previous meta-analyses for 1980 to 1995.

Data Selection.
—We selected long-term studies that assessed major disease end points as an outcome. For the meta-analysis, we chose placebo-controlled randomized trials. For randomized trials using surrogate end points such as blood pressure, we selected the largest studies that evaluated multiple drugs. Where clinical trial evidence was lacking, we relied on information from observational studies.

Data Synthesis.
—Diuretics and β-blockers have been evaluated in 18 long-term randomized trials. Compared with placebo, β-blocker therapy was effective in perventing stroke (relative risk [RR], 0.71; 95% confidence interval [CI], 0.59-0.86) and congestive heart failure (RR, 0.58; 95% CI, 0.40-0.84). The findings were similar for high-dose diuretic therapy (for stroke, RR, 0.49; 95% CI, 0.39-0.62; and for congestive heart failure, RR, 0.17; 95% Cl, 0.07-0.41). Low-dose diuretic therapy prevented not only stroke (RR, 0.66; 95% CI, 0.55-0.78) and congestive heart failure (RR, 0.58; 95% CI, 0.44-0.76) but also coronary disease (RR, 0.72; 95% CI, 0.61-0.85) and total mortality (RR, 0.90; 95% CI, 0.81-0.99). Although calcium channel blockers and angiotensin-converting enzyme (ACE) inhibitors reduce blood pressure in hypertensive patients, the clinical trial evidence in terms of health outcomes is meager. For several short-acting dihydropyridine calcium channel blockers, the available evidence suggests the possibility of harm. Whether the long-acting formulations and the nondihydropyridine calcium channel blockers are safe and prevent major cardiovascular events in patients with hypertension remains untested and therefore unknown.

Conclusion.
—Until the results of large long-term clinical trials evaluating the effects of calcium channel blockers and ACE inhibitors on cardiovascular disease incidence are completed, the available scientific evidence provides strong support for the current national guidelines, which recommend diuretics and β-blockers as firstline agents and low-dose therapy for all antihypertensive agents.

Author Affiliations
From the Cardiovascular Health Research Unit, Departments of Medicine (Drs Psaty, Siscovick, and Koepsell), Epidemiology (Drs Psaty, Smith, Siscovick, Koepsell, Weiss, Heckbert, and Lemaitre), and Health Services (Drs Psaty, Koepsell, and Wagner), University of Washington, and the Center for Health Studies, Group Health Cooperative of Puget Sound (Dr Wagner), Seattle, Wash; and the Department of Public Health Sciences, Bowman Gray School of Medicine, Winston-Salem, NC (Dr Furberg).

Footnotes
Dr Furberg has received research grants from Pfizer and Wyeth-Ayerst and in 1996 received fees for lectures sponsored by Merck and Bristol-Myers Squibb. He also serves on the Data Safety Monitoring Boards for Parke-Davis and Searle. Dr Psaty serves on the Events Committee of a clinical trial funded by Wyeth-Ayerst.

Reprints: Bruce M. Psaty, MD, PhD, Cardiovascular Health Research Unit, Suite 1360,1730 Minor Ave, Seattle, WA 98101.

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter     What's this?

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

{beta}-Adrenergic Antagonists in Hypertension: A Review of the Evidence
Warmack et al.
The Annals of Pharmacotherapy 2009;43:2031-2043.
ABSTRACT | FULL TEXT  

Hypertension Improvement Project: Randomized Trial of Quality Improvement for Physicians and Lifestyle Modification for Patients
Svetkey et al.
Hypertension 2009;54:1226-1233.
ABSTRACT | FULL TEXT  

Beta-blockers for hypertension: Are they going out of style?
CHE et al.
Cleveland Clinic Journal of Medicine 2009;76:533-542.
ABSTRACT | FULL TEXT  

Prescription of antihypertensive agents to haemodialysis patients: time trends and associations with patient characteristics, country and survival in the DOPPS
Lopes et al.
Nephrol Dial Transplant 2009;24:2809-2816.
ABSTRACT | FULL TEXT  

{beta}-Blocker Use for the Stages of Heart Failure
Klapholz
Mayo Clin Proc. 2009;84:718-729.
ABSTRACT | FULL TEXT  

How Optimal is the Medical Management of Patients Prior to Major Reconstructive Vascular Surgery? The Results of a Cross-sectional Study
Marshall et al.
VASC ENDOVASCULAR SURG 2009;43:238-243.
ABSTRACT  

ALLHAT Findings Revisited in the Context of Subsequent Analyses, Other Trials, and Meta-analyses
Wright et al.
Arch Intern Med 2009;169:832-842.
ABSTRACT | FULL TEXT  

Standards of Medical Care in Diabetes--2009
American Diabetes Association
Diabetes Care 2009;32:S13-S61.
FULL TEXT  

Thiazide-Type Diuretics and {beta}-Adrenergic Blockers as First-Line Drug Treatments for Hypertension
Cutler and Davis
Circulation 2008;117:2691-2705.
FULL TEXT  

Prevention of Heart Failure: A Scientific Statement From the American Heart Association Councils on Epidemiology and Prevention, Clinical Cardiology, Cardiovascular Nursing, and High Blood Pressure Research; Quality of Care and Outcomes Research Interdisciplinary Working Group; and Functional Genomics and Translational Biology Interdisciplinary Working Group
Schocken et al.
Circulation 2008;117:2544-2565.
ABSTRACT | FULL TEXT  

Standards of Medical Care in Diabetes--2008
American Diabetes Association
Diabetes Care 2008;31:S12-S54.
FULL TEXT  

Joint effects of history of hypertension at baseline and type 2 diabetes at baseline and during follow-up on the risk of coronary heart disease
Hu et al.
Eur Heart J 2007;28:3059-3066.
ABSTRACT | FULL TEXT  

Stroke and Its Prevention in Chronic Kidney Disease
Khella and Bleicher
CJASN 2007;2:1343-1351.
ABSTRACT | FULL TEXT  

Cardiovascular Protection Using Beta-Blockers: A Critical Review of the Evidence
Bangalore et al.
J Am Coll Cardiol 2007;50:563-572.
ABSTRACT | FULL TEXT  

Predictive Utility of Pulse Pressure and Other Blood Pressure Measures for Cardiovascular Outcomes
Mosley et al.
Hypertension 2007;49:1256-1264.
ABSTRACT | FULL TEXT  

Modest weight gain is associated with sympathetic neural activation in nonobese humans
Gentile et al.
Am. J. Physiol. Regul. Integr. Comp. Physiol. 2007;292:R1834-R1838.
ABSTRACT | FULL TEXT  

Clinical Trials for Hypertension: Expectations Fulfilled and Unfulfilled
Kaplan
Hypertension 2007;49:257-259.
FULL TEXT  

Which cardiovascular risk factors matter in chronic kidney disease?
Baigent and Landray
Nephrol Dial Transplant 2007;22:9-11.
FULL TEXT  

The Year in Hypertension
Williams
J Am Coll Cardiol 2006;48:1698-1711.
FULL TEXT  

Clinical trials in hypertension.
Messerli et al.
JAMA 2006;296:1463-1463.
FULL TEXT  

Clinical Trials in Hypertension--Reply
Psaty et al.
JAMA 2006;296:1464-1465.
FULL TEXT  

Clinical Events in High-Risk Hypertensive Patients Randomly Assigned to Calcium Channel Blocker Versus Angiotensin-Converting Enzyme Inhibitor in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial
Leenen et al.
Hypertension 2006;48:374-384.
ABSTRACT | FULL TEXT  

Thiazide-Associated Glucose Abnormalities: Prognosis, Etiology, and Prevention: Is Potassium Balance the Key?
Cutler
Hypertension 2006;48:198-200.
FULL TEXT  

Primary Prevention of Ischemic Stroke: A Guideline From the American Heart Association/American Stroke Association Stroke Council: Cosponsored by the Atherosclerotic Peripheral Vascular Disease Interdisciplinary Working Group; Cardiovascular Nursing Council; Clinical Cardiology Council; Nutrition, Physical Activity, and Metabolism Council; and the Quality of Care and Outcomes Research Interdisciplinary Working Group: The American Academy of Neurology affirms the value of this guideline.
Goldstein et al.
Circulation 2006;113:e873-e923.
ABSTRACT | FULL TEXT  

Primary Prevention of Ischemic Stroke: A Guideline From the American Heart Association/American Stroke Association Stroke Council: Cosponsored by the Atherosclerotic Peripheral Vascular Disease Interdisciplinary Working Group; Cardiovascular Nursing Council; Clinical Cardiology Council; Nutrition, Physical Activity, and Metabolism Council; and the Quality of Care and Outcomes Research Interdisciplinary Working Group: The American Academy of Neurology affirms the value of this guideline.
Goldstein et al.
Stroke 2006;37:1583-1633.
ABSTRACT | FULL TEXT  

Role of Diuretics in the Prevention of Heart Failure: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial
Davis et al.
Circulation 2006;113:2201-2210.
ABSTRACT | FULL TEXT  

Recent Trials in Hypertension: Compelling Science or Commercial Speech?
Psaty et al.
JAMA 2006;295:1704-1706.
FULL TEXT  

ACC/AHA 2005 Guidelines for the Management of Patients With Peripheral Arterial Disease (Lower Extremity, Renal, Mesenteric, and Abdominal Aortic): Executive Summary A Collaborative Report From the American Association for Vascular Surgery/Society for Vascular Surgery, Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine and Biology, Society of Interventional Radiology, and the ACC/AHA Task Force on Practice Guidelines (Writing Committee to Develop Guidelines for the Management of Patients With Peripheral Arterial Disease): Endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation; National Heart, Lung, and Blood Institute; Society for Vascular Nursing; TransAtlantic Inter-Society Consensus; and Vascular Disease Foundation
Hirsch et al.
J Am Coll Cardiol 2006;47:1239-1312.
FULL TEXT  

Antihypertensive Medication Use Among US Adults With Hypertension
Gu et al.
Circulation 2006;113:213-221.
ABSTRACT | FULL TEXT  

The Impact of History of Hypertension and Type 2 Diabetes at Baseline on the Incidence of Stroke and Stroke Mortality
Hu et al.
Stroke 2005;36:2538-2543.
ABSTRACT | FULL TEXT  

Public awareness of heart failure in Europe: first results from SHAPE
Remme et al.
Eur Heart J 2005;26:2413-2421.
ABSTRACT | FULL TEXT  

Calcium Antagonists: Effects on Cardio-Renal Risk in Hypertensive Patients
Nathan et al.
Hypertension 2005;46:637-642.
ABSTRACT | FULL TEXT  

Persistence with Treatment in Newly Treated Middle-Aged Patients with Essential Hypertension
Perreault et al.
The Annals of Pharmacotherapy 2005;39:1401-1408.
ABSTRACT | FULL TEXT  

Challenges in Systematic Reviews That Assess Treatment Harms
Chou and Helfand
ANN INTERN MED 2005;142:1090-1099.
ABSTRACT | FULL TEXT  

Hypertension Management in the Elderly Has Improved: Ontario Prescribing Trends, 1994 to 2002
Tu et al.
Hypertension 2005;45:1113-1118.
ABSTRACT | FULL TEXT  

Recent hypertension trials: Implications and controversies
Williams
J Am Coll Cardiol 2005;45:813-827.
ABSTRACT | FULL TEXT  

Association of Intentional Changes in Body Weight with Coronary Heart Disease Event Rates in Overweight Subjects Who Have an Additional Coronary Risk Factor
Eilat-Adar et al.
Am J Epidemiol 2005;161:352-358.
ABSTRACT | FULL TEXT  

Highlighting the need for better patient care in stable angina: results of the international Angina Treatment Patterns (ATP) Survey in 7074 patients
Eastaugh et al.
Fam Pract 2005;22:43-50.
ABSTRACT | FULL TEXT  

Translating Research into Practice: Are Physicians Following Evidence-Based Guidelines in the Treatment of Hypertension?
Holmes et al.
Med Care Res Rev 2004;61:453-473.
ABSTRACT  

The PROGRESS trial three years later: time for a balanced report of effectiveness
Wennberg and Zimmermann
BMJ 2004;329:968-970.
FULL TEXT  

Chlorthalidone vs Other Low-Dose Diuretics--Reply
Psaty et al.
JAMA 2004;292:1817-1817.
FULL TEXT  

Tips for learners of evidence-based medicine: 1. Relative risk reduction, absolute risk reduction and number needed to treat
Barratt et al.
CMAJ 2004;171:353-358.
FULL TEXT  

Expert consensus document on {beta}-adrenergic receptor blockers: The Task Force on Beta-Blockers of the European Society of Cardiology
Task Force Members et al.
Eur Heart J 2004;25:1341-1362.
FULL TEXT  

A Practical and Evidence-Based Approach to Cardiovascular Disease Risk Reduction
Gluckman et al.
Arch Intern Med 2004;164:1490-1500.
ABSTRACT | FULL TEXT  

Hypertensive Therapy: Part II
Franco et al.
Circulation 2004;109:3081-3088.
FULL TEXT  

Atherosclerotic Vascular Disease Conference: Writing Group V: Medical Decision Making and Therapy
Creager et al.
Circulation 2004;109:2634-2642.
FULL TEXT  

Use of diuretics in cardiovascular disease: (2) hypertension
Shah et al.
Postgrad. Med. J. 2004;80:271-276.
ABSTRACT | FULL TEXT  

Analysis of Cause-Specific Mortality in the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) Study
Steinberg et al.
Circulation 2004;109:1973-1980.
ABSTRACT | FULL TEXT  

Impact of Combination Evidence-Based Medical Therapy on Mortality in Patients With Acute Coronary Syndromes
Mukherjee et al.
Circulation 2004;109:745-749.
ABSTRACT | FULL TEXT  

Antihypertensive Therapy and Incidence of Type 2 Diabetes: A systematic review
Padwal and Laupacis
Diabetes Care 2004;27:247-255.
ABSTRACT | FULL TEXT  

Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure
Chobanian et al.
Hypertension 2003;42:1206-1252.
ABSTRACT | FULL TEXT  

Do Thiazide Diuretics Confer Specific Protection Against Strokes?
Messerli et al.
Arch Intern Med 2003;163:2557-2560.
ABSTRACT | FULL TEXT  

`Size is not everything`: the Antihypertensive and Lipid-Lowering treatment to prevent Heart Attack Trial (ALLHAT): The ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. Major outcomes in high-risk hypertensive patients randomised to angiotensin-converting enzyme inhibitor or calcium channel blocker versus diuretic. The Antihypertensive and Lipid-Lowering treatment to prevent Heart Attack Trial (ALLHAT)
Mcinnes
British Journal of Diabetes & Vascular Disease 2003;3:263-267.
ABSTRACT  

Value of low dose combination treatment with blood pressure lowering drugs: analysis of 354 randomised trials
Law et al.
BMJ 2003;326:1427.
ABSTRACT | FULL TEXT  

The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: The JNC 7 Report
Chobanian et al.
JAMA 2003;289:2560-2571.
ABSTRACT | FULL TEXT  

Health Outcomes Associated With Various Antihypertensive Therapies Used as First-Line Agents: A Network Meta-analysis
Psaty et al.
JAMA 2003;289:2534-2544.
ABSTRACT | FULL TEXT  

Long-term Cardiovascular Consequences of Diuretics vs Calcium Channel Blockers vs Angiotensin-Converting Enzyme Inhibitors--Reply
Wright et al.
JAMA 2003;289:2069-2070.
FULL TEXT  

Management of High Blood Pressure in African Americans: Consensus Statement of the Hypertension in African Americans Working Group of the International Society on Hypertension in Blacks
Douglas et al.
Arch Intern Med 2003;163:525-541.
FULL TEXT  

Initial Treatment of Hypertension
August
NEJM 2003;348:610-617.
FULL TEXT  

Major Outcomes in High-Risk Hypertensive Patients Randomized to Angiotensin-Converting Enzyme Inhibitor or Calcium Channel Blocker vs Diuretic: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT)
The ALLHAT Officers and Coordinators for the ALLHA
JAMA 2002;288:2981-2997.
ABSTRACT | FULL TEXT  

The Verdict From ALLHAT--Thiazide Diuretics Are the Preferred Initial Therapy for Hypertension
Appel
JAMA 2002;288:3039-3042.
FULL TEXT  

Time Trends in High Blood Pressure Control and the Use of Antihypertensive Medications in Older Adults: The Cardiovascular Health Study
Psaty et al.
Arch Intern Med 2002;162:2325-2332.
ABSTRACT | FULL TEXT  

Control of Hypertension and Risk of Stroke Recurrence
Friday et al.
Stroke 2002;33:2652-2657.
ABSTRACT | FULL TEXT  

New Evidence for Stroke Prevention: Scientific Review
Straus et al.
JAMA 2002;288:1388-1395.
ABSTRACT | FULL TEXT  

Uric Acid, Hominoid Evolution, and the Pathogenesis of Salt-Sensitivity
Watanabe et al.
Hypertension 2002;40:355-360.
ABSTRACT | FULL TEXT  

Serum potassium level and dietary potassium intake as risk factors for stroke
Green et al.
Neurology 2002;59:314-320.
ABSTRACT | FULL TEXT  

Physiological significance of alpha 2-adrenergic receptor subtype diversity: one receptor is not enough
Philipp et al.
Am. J. Physiol. Regul. Integr. Comp. Physiol. 2002;283:R287-R295.
ABSTRACT | FULL TEXT  

Diuretic Therapy, the {alpha}-Adducin Gene Variant, and the Risk of Myocardial Infarction or Stroke in Persons With Treated Hypertension
Psaty et al.
JAMA 2002;287:1680-1689.
ABSTRACT | FULL TEXT  

J-Shaped Relationship between Blood Pressure and Mortality in Hypertensive Patients: New Insights from a Meta-Analysis of Individual-Patient Data
Boutitie et al.
ANN INTERN MED 2002;136:438-448.
ABSTRACT | FULL TEXT  

Screening for traditional risk factors for cardiovascular disease: A review for oral health care providers
GLICK
Journal of the American Dental Association 2002;133:291-300.
ABSTRACT | FULL TEXT  

Superior Physicians and the Treatment of Hypertension
Cohen
Arch Intern Med 2002;162:387-388.
FULL TEXT  

First-line treatment for hypertension
Jackson and Ramsay
Eur Heart J 2002;23:179-182.
FULL TEXT  

Modulation of {beta}-adrenergic receptor subtype activities in perioperative medicine: mechanisms and sites of action
Zaugg et al.
Br J Anaesth 2002;88:101-123.
ABSTRACT | FULL TEXT  

Development of Predictive Models for Long-Term Cardiovascular Risk Associated With Systolic and Diastolic Blood Pressure
Glynn et al.
Hypertension 2002;39:105-110.
ABSTRACT | FULL TEXT  

Impact of High-Normal Blood Pressure on the Risk of Cardiovascular Disease
Vasan et al.
NEJM 2001;345:1291-1297.
ABSTRACT | FULL TEXT  

Guidelines for the Management of Patients with Chronic Stable Angina: Treatment
Fihn et al.
ANN INTERN MED 2001;135:616-632.
ABSTRACT | FULL TEXT  

Quality Indicators for Appropriate Medication Use in Vulnerable Elders
Knight and Avorn
ANN INTERN MED 2001;135:703-710.
FULL TEXT  

Differences Between Primary vs Secondary Prevention Trials Regarding the Stroke Protective Effect of Antihypertensive Drugs
Fournier et al.
Arch Intern Med 2001;161:2152-2153.
FULL TEXT  

Comparison of Evidence of Treatment Effects in Randomized and Nonrandomized Studies
Ioannidis et al.
JAMA 2001;286:821-830.
ABSTRACT | FULL TEXT  

Association Between Blood Pressure Level and the Risk of Myocardial Infarction, Stroke, and Total Mortality: The Cardiovascular Health Study
Psaty et al.
Arch Intern Med 2001;161:1183-1192.
ABSTRACT | FULL TEXT  

Evidence based management of hypertension: What are the elements of good treatment for hypertension?
Mulrow and Pignone
BMJ 2001;322:1107-1109.
FULL TEXT  

Review: The management of the elderly with hypertension
Bulpitt
Journal of Renin-Angiotensin-Aldosterone System 2001;2:11-13.
 

Sick genes, sick individuals or sick populations with chronic disease? The emergence of diabetes and high blood pressure in African-origin populations
Cruickshank et al.
Int J Epidemiol 2001;30:111-117.
ABSTRACT | FULL TEXT  

Antihypertensive Drug Therapies and the Risk of Ischemic Stroke
Klungel et al.
Arch Intern Med 2001;161:37-43.
ABSTRACT | FULL TEXT  

Primary Prevention of Ischemic Stroke : A Statement for Healthcare Professionals From the Stroke Council of the American Heart Association
Goldstein et al.
Circulation 2001;103:163-182.
FULL TEXT  

Dementia and Disability Outcomes in Large Hypertension Trials: Lessons Learned from the Systolic Hypertension in the Elderly Program (SHEP) Trial
Di Bari et al.
Am J Epidemiol 2001;153:72-78.
ABSTRACT | FULL TEXT  

Primary Prevention of Ischemic Stroke : A Statement for Healthcare Professionals From the Stroke Council of the American Heart Association
Goldstein et al.
Stroke 2001;32:280-299.
FULL TEXT  

Baseline Characteristics of Participants in the Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT)
Grimm et al.
Hypertension 2001;37:19-27.
ABSTRACT | FULL TEXT  

Vascular events in hypertensive patients with systemic lupus erythematosus
Rahman et al.
Lupus 2000;9:672-675.
ABSTRACT  

Hypertension and Its Treatment in Postmenopausal Women : Baseline Data from the Women's Health Initiative
Wassertheil-Smoller et al.
Hypertension 2000;36:780-789.
ABSTRACT | FULL TEXT  

Low-Dose Hydrochlorothiazide and Preservation of Bone Mineral Density in Older Adults: A Randomized, Double-Blind, Placebo-Controlled Trial
LaCroix et al.
ANN INTERN MED 2000;133:516-526.
ABSTRACT | FULL TEXT  

There is a non-linear relationship between mortality and blood pressure
Port et al.
Eur Heart J 2000;21:1635-1638.
 

National Guidelines, Clinical Trials, and Quality of Evidence
Psaty et al.
Arch Intern Med 2000;160:2577-2580.
FULL TEXT  

Association of systolic blood pressure with macrovascular and microvascular complications of type 2 diabetes (UKPDS 36): prospective observational study
Adler et al.
BMJ 2000;321:412-419.
ABSTRACT | FULL TEXT  

Choosing a first-line drug in the management of elevated blood pressure: What is the evidence? 1: Thiazide diuretics
Wright
CMAJ 2000;163:57-60.
ABSTRACT | FULL TEXT