JAMA. 2002 Dec 18;288(23):2981-97. Related Articles， Links ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial.

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<.001) groups compared with chlorthalidone， and 5-year diastolic blood pressure was significantly lower with amlodipine (0.8 mm Hg， P<.001). For amlodipine vs chlorthalidone， secondary outcomes were similar except for a higher 6-year rate of HF with amlodipine (10.2% vs 7.7%; RR， 1.38; 95% CI， 1.25-1.52). For lisinopril vs chlorthalidone， lisinopril had higher 6-year rates of combined CVD (33.3% vs 30.9%; RR， 1.10; 95% CI， 1.05-1.16); stroke (6.3% vs 5.6%; RR， 1.15; 95% CI， 1.02-1.30); and HF (8.7% vs 7.7%; RR， 1.19; 95% CI， 1.07-1.31).

CONCLUSION: Thiazide-type diuretics are superior in preventing 1 or more major forms of CVD and are less expensive. They should be preferred for first-step antihypertensive therapy.