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ACE Inhibitors vs. Diuretics for Hypertension: Round II

An Australian trial challenges the U.S. ALLHAT study.

In the recent ALLHAT double-blind randomized trial, U.S. researchers found that a thiazide diuretic (chlorthalidone) was the most effective of several first-line therapies for hypertension, including the ACE inhibitor lisinopril (Journal Watch Cardiology Jan 31 2003). Now, Australian researchers have conducted an open-label randomized trial of hydrochlorothiazide (3039 subjects) versus enalapril (3044 subjects) in hypertensive patients (age range, 65-84; 95% white; mean BP, 168/91 mm Hg) recruited from family-practice settings. Among the exclusion criteria were any recent adverse cardiovascular events and serum creatinine level >2.5 mg/dL. The study was partly supported by a manufacturer of enalapril.

The randomization protocol served as a recommendation; the final decision lay with each patient's physician. In both groups, 83% were initially treated according to randomized assignment.

During a median 4-year follow-up, BP reduction was similar in the 2 groups (about –25/–10 mm Hg). Incidence of the primary endpoint (all adverse cardiovascular events or death from any cause) was lower with enalapril than with hydrochlorothiazide (695 vs. 736 events; hazard ratio, 0.89; 95% CI, 0.79-1.00; P=0.05), with post-hoc subgroup analyses showing a significant benefit in men but not in women. The number needed to treat was 32 overall and 23 in men. All-cause mortality incidence trended slightly lower with enalapril but did not reach significance.

Comment: ALLHAT and this trial are both community-based studies of first-line therapy for hypertension, the former favoring the diuretic and the latter the ACE inhibitor. However, the diuretics and ACE inhibitors tested were not the same in these 2 trials. Also, the diuretic yielded better BP control in ALLHAT, whereas both drug types controlled BP similarly in this study. In addition, the ALLHAT study population was younger, was more racially diverse, and had more comorbidities. An editorialist still generally favors diuretics, except when ACE inhibitors are specifically indicated. The bottom line is that this study's results challenge the initial persuasiveness of the ALLHAT findings; the best overall choice of first-line treatment for hypertension now appears unclear. An individual patient's needs and characteristics often will provide the best guidance for which treatment or combination of treatments to use.

— Harlan M. Krumholz, MD, SM

Published in Journal Watch Cardiology March 21, 2003

Citation(s):

Wing LMH et al. for the Second Australian National Blood Pressure Study Group. A comparison of outcomes with angiotensin-converting-enzyme inhibitors and diuretics for hypertension in the elderly. N Engl J Med 2003 Feb 13; 348:583-92.

• Medline abstract (Free)

Frohlich ED. Treating hypertension -- What are we to believe? N Engl J Med 2003 Feb 13; 348:639-41.

• Medline abstract (Free)

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