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Diuretics Superior to Alpha-Blockers for Hypertension

The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) is a randomized, double-blind, controlled study intended to compare outcomes for hypertensive patients treated with various classes of medications. One arm of the study was stopped after an interim analysis revealed worse outcomes for patients treated with the alpha-blocker doxazosin than for patients treated with diuretics. The analysis reported in this paper involved 24,335 patients older than 55 who had hypertension and at least 1 other coronary risk factor. These patients were assigned randomly to treatment with either chlorthalidone (12.5 to 25 mg/day) or doxazosin (2 to 8 mg/day).

The planned follow-up for the study is 4 to 8 years, but the doxazosin arm was stopped after a median follow-up of 3.3 years. Compared with the diuretic group, the doxazosin group had significantly greater risk for coronary heart disease events (12.0 vs. 13.1 events per 100 patients), stroke (3.6 vs. 4.3 events per 100 patients) and all cardiovascular events (21.8 vs. 25.5 events per 100 patients). The increased risk for cardiovascular events was apparent in subgroups defined by age, race, and diabetic status.

Comment: This early report shows that alpha-blockers should not be a first-line antihypertensive therapy, and reestablishes diuretics as the gold standard that newer drugs must surpass. ALLHAT ultimately will provide comparisons of diuretic therapy with calcium-blocker or angiotensin-converting-enzyme inhibitor treatment as well.

— TH Lee

Published in Journal Watch General Medicine May 2, 2000

Citation(s):

The ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. Major cardiovascular events in hypertensive patients randomized to doxazosin vs chlorthalidone: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). JAMA 2000 Apr 19 283 1967-1975.

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