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)

• Published in: JAMA : the journal of the American Medical Association 2002-12, Vol.288 (23), p.2981-2997
• Main Authors: Furberg, Curt D, Wright, Jackson T, Davis, Barry R, Cutler, Jeffrey A
• Format: Article
• Language: English
• Subjects: Aged; Amlodipine - economics; Amlodipine - therapeutic use; Angiotensin-Converting Enzyme Inhibitors - economics; Angiotensin-Converting Enzyme Inhibitors - therapeutic use; Antihypertensive agents; Antihypertensive Agents - economics; Antihypertensive Agents - therapeutic use; Biological and medical sciences; Calcium Channel Blockers - economics; Calcium Channel Blockers - therapeutic use; Cardiovascular Diseases - epidemiology; Cardiovascular Diseases - prevention & control; Cardiovascular system; Chlorthalidone - economics; Chlorthalidone - therapeutic use; Clinical outcomes; Clinical trials; Diuretics - economics; Diuretics - therapeutic use; Double-Blind Method; Enzymes; Female; Health risk assessment; Heart attacks; Humans; Hypertension - drug therapy; Lipids; Lisinopril - economics; Lisinopril - therapeutic use; Male; Medical sciences; Middle Aged; Neurotransmitters; Patients; Pharmacology. Drug treatments; Prevention; Proportional Hazards Models; Risk Factors; Treatment Outcome
• ISSN: 0098-7484; 1538-3598
• DOI: 10.1001/jama.288.23.2981

CONTEXT Antihypertensive therapy is well established to reduce hypertension-related morbidity and mortality, but the optimal first-step therapy is unknown. OBJECTIVE To determine whether treatment with a calcium channel blocker or an angiotensin-converting enzyme inhibitor lowers the incidence of coronary heart disease (CHD) or other cardiovascular disease (CVD) events vs treatment with a diuretic. DESIGN The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), a randomized, double-blind, active-controlled clinical trial conducted from February 1994 through March 2002. SETTING AND PARTICIPANTS A total of 33 357 participants aged 55 years or older with hypertension and at least 1 other CHD risk factor from 623 North American centers. INTERVENTIONS Participants were randomly assigned to receive chlorthalidone, 12.5 to 25 mg/d (n = 15 255); amlodipine, 2.5 to 10 mg/d (n = 9048); or lisinopril, 10 to 40 mg/d (n = 9054) for planned follow-up of approximately 4 to 8 years. MAIN OUTCOME MEASURES The primary outcome was combined fatal CHD or nonfatal myocardial infarction, analyzed by intent-to-treat. Secondary outcomes were all-cause mortality, stroke, combined CHD (primary outcome, coronary revascularization, or angina with hospitalization), and combined CVD (combined CHD, stroke, treated angina without hospitalization, heart failure [HF], and peripheral arterial disease). RESULTS Mean follow-up was 4.9 years. The primary outcome occurred in 2956 participants, with no difference between treatments. Compared with chlorthalidone (6-year rate, 11.5%), the relative risks (RRs) were 0.98 (95% CI, 0.90-1.07) for amlodipine (6-year rate, 11.3%) and 0.99 (95% CI, 0.91-1.08) for lisinopril (6-year rate, 11.4%). Likewise, all-cause mortality did not differ between groups. Five-year systolic blood pressures were significantly higher in the amlodipine (0.8 mm Hg, P = .03) and lisinopril (2 mm Hg, P