Major cardiovascular events in hypertensive patients randomized to doxazosin vs chlorthalidone - The Antihypertensive and Lipid-Lowering Treatment toPrevent Heart Attack Trial (ALLHAT)

Context Hypertension is associated with a significantly increased risk of m orbidity and mortality. Only diuretics and beta-blockers have been shown to reduce this risk in long-term clinical trials: Whether newer antihypertens ive agents reduce the incidence of cardiovascular disease (CVD) is unknown. Objective To compare the effect of doxazosin, an alpha-blocker, with chlort halidone, a diuretic, on incidence of CVD in patients with hypertension as part of a study of 4 types of antihypertensive drugs: chlorthalidone, doxaz osin, amlodipine, and lisinopril. Design Randomized, double-blind, active-controlled clinical trial, the Anti hypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial, in itiated in February 1994. In January 2000, after an interim analysis, an in dependent data review committee recommended discontinuing the doxazosin tre atment arm based on comparisons with chlorthalidone. Therefore, outcomes da ta presented herein reflect follow-up through December 1999. Setting A total of 625 centers in the United States and Canada. Participants A total of 24335 patients (aged greater than or equal to 55 ye ars) with hypertension and at least 1 other coronary heart disease (CHD) ri sk factor who received either doxazosin or chlorthialidone. Interventions Participants were randomly assigned to receive chlorthalidone , 12.5 to 25 mg/d (n = 15268), or doxazosin, 2 to 8 mg/d (n = 9067), for a planned follow-up of 4 to 8 years. Main Outcome Measures The primary outcome measure was fatal CHD or nonfatal myocardial infarction.(MI), analyzed by intent to treat; secondary outcome measures included all-cause mortality, stroke, and combined CVD (CHD death , nonfatal MI, stroke, angina, coronary revascularization, congestive heart failure [CHF], and peripheral arterial disease); com pared by the chlortha lidone group vs the doxazosin group. Results Median follow-up was 3.3 years. A total of 365 patients in the doxa zosin group and 608 in the chlorthalidone group had fatal CHD or nonfatal M I, with no difference in risk between the groups (relative risk [RR], 1.03; 95 % confidence interval [CI], 0.90-1.17; P = .71). Total mortality did no t differ between the doxazosin and chlorthalidone arms (4-year rates, 9.62 % and 9.08 %, respectively; RR, 1.03; 95 % CI, 0.90-1.15; P = .56.) The dox azosin arm, compared with the chlorthalidone arm, had a higher risk of stro ke (RR, 1.19; 95 % CI, 1.01-1.40; P = .04) and combined CVD (4-year rates, 25.45% vs 21.76 %; RR, 1.25; 95 % CI, 1.17-1.33; P < .001). Considered sepa rately, CHF risk was doubled (4-year rates, 8.13 % vs 4.45 %; RR, 2.04; 95 % CI, 1.79-2.32; P < .001); RRs for angina, coronary revascularization, and peripheral arterial disease were 1.16 (P < .001), 1.15 (P = .05), and 1.07 (P = .50), respectively. Conclusion Our data indicate that compared with doxazosin, chlorthalidone y ields essentially equal risk of CHD death/nonfatal MI but significantly red uces the risk of combined CVD events, particularly CHF, in high-risk hypert ensive patients.