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Another Study of First-Line Antihypertensive Therapy

Results from a new randomized trial differ from those from ALLHAT but don't necessarily complicate the question of which first-line therapy is best.

Results from the recently published American ALLHAT study suggested that the diuretic chlorthalidone was at least as good as the angiotensin-converting-enzyme (ACE) inhibitor lisinopril as first-line therapy for hypertension (Journal Watch Jan 14 2003). Now, findings from another study supported by both the Australian government and a maker of the ACE inhibitor enalapril, yield a slightly different conclusion.

In an open-label, randomized trial, 6083 hypertensive patients (mean blood pressure, 168/91 mm Hg) received either a diuretic or an ACE inhibitor as initial therapy. Hydrochlorothiazide and enalapril, respectively, were recommended (but not mandatory); additional drugs were given when monotherapy was inadequate. The patients' age range was 65 to 84; nearly all patients were white, and very few had diabetes or known coronary disease.

During 4 years of follow-up, extent of BP reduction was identical in the 2 groups. The frequency of the primary outcome -- all cardiovascular events or death from any cause -- was 56 per 1000 patient-years in the ACE inhibitor group and 60 per 1000 patient-years in the diuretic group, which was a barely significant difference (P=0.05). The ACE inhibitor group had a significantly lower rate of myocardial infarction but not of stroke or overall mortality.

Comment: The differing outcomes of this study and ALLHAT should not necessarily generate confusion: This study included relatively healthy white elders with few risk factors; in contrast, the baseline prevalence of cardiovascular disease and risk factors was much higher in the younger and racially mixed ALLHAT population. An editorialist reviews the 2 studies side by side and concludes that initial diuretic therapy still is appropriate, unless coexisting conditions indicate ACE inhibitors. A review article in the same issue of the New England Journal of Medicine provides a nice update on initial treatment for hypertension.

— Allan S. Brett, MD

Published in Journal Watch General Medicine February 21, 2003

Citation(s):

Wing LMH et al. 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.

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• Medline abstract (Free)

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

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August P. Initial treatment of hypertension. N Engl J Med 2003 Feb 13; 348:610-7.

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• Medline abstract (Free)