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Finally, the ALLHAT Results for Hypertension

The thiazide diuretic chlorthalidone was at least as effective as lisinopril or amlodipine for preventing adverse coronary events among older hypertensive patients.

To settle the debate about first-line drug therapy for hypertension, the NIH sponsored the Antihypertensive and Lipid-Lowering treatment to prevent Heart Attack Trial (ALLHAT). The long-awaited results now have been published.

This double-blind, randomized trial involved 33,357 people (age, 55 or older) with hypertension and at least 1 other coronary risk factor. Participants received the thiazide diuretic chlorthalidone, the calcium-channel blocker amlodipine, the angiotensin-converting-enzyme inhibitor lisinopril, or the -blocker doxazosin. Patients who needed additional medication were given open-label atenolol, reserpine, or clonidine. The doxazosin arm was terminated in 2000 because of a high incidence of congestive heart failure in this group (Journal Watch May 2 2000). In the current report, the other 3 treatments are compared.

After an average follow-up of 5 years, there were no differences between groups in the primary outcome (fatal coronary disease or nonfatal MI) or in all-cause mortality. However, compared with the chlorthalidone group, the amlodipine group had a significantly higher 6-year cumulative incidence of heart failure (7.7% vs. 10.2%), and the lisinopril group had significantly higher 6-year rates of heart failure (7.7% vs. 8.7%), stroke (5.6% vs. 6.3%), and angina (12.1% vs. 13.6%).

Comment: In this landmark trial, initial therapy with a diuretic was as good as therapy with a calcium-channel blocker or an ACE inhibitor; for several outcomes, diuretic therapy appeared to be better. Numerous questions come to mind: For example, is chlorthalidone equivalent to the more widely used hydrochlorothiazide? What about the role of ß-blockers, which were not a first-line treatment in this trial? Nevertheless, an editorialist argues that ALLHAT's results are "robust, unambiguous, and generalizable," and that thiazides should be the initial treatment choice for most hypertensive patients.

— Allan S. Brett, MD

Published in Journal Watch General Medicine January 14, 2003

Citation(s):

The ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. 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). JAMA 2002 Dec 18; 288:2981-97.

• Original article (Subscription may be required)
• Medline abstract (Free)

Appel LJ. The verdict from ALLHAT -- Thiazide diuretics are the preferred initial therapy for hypertension. JAMA 2002 Dec 18; 288:3039-42.

• Original article (Subscription may be required)
• Medline abstract (Free)