Commentary

A study of astonishing methodological beauty, ALLHAT is a large, simple, practice based, double blind, active comparison trial that poses important public health questions about the effects of first line antihypertensive therapies on major health outcomes, including MI, stroke, and HF. This combination of excellent methods and outstanding questions means that the findings merit careful attention, wide dissemination, and clinical translation.

In ALLHAT, neither the calcium channel blocker amlodipine nor the ACE inhibitor lisinopril was better than the low dose diuretic chlorthalidone for any primary or secondary outcome. Conversely, low dose diuretics were superior to amlodipine or lisinopril for at least 1 major disease outcome. Low dose diuretics alone should be the first line drug therapy for hypertension.

For patients starting drug therapy, low dose diuretics should be the initial therapy for uncomplicated hypertension, although it may take 4 weeks to achieve maximum effect. If blood pressure (BP) is not controlled on diuretics alone, a second drug should be added. Many patients are already treated, but not with a diuretic. For those with uncontrolled BP on a non-diuretic regimen, a low dose diuretic should be added. If BP is controlled with a non-diuretic, the patient should be switched to a low-dose diuretic.

The ALLHAT trial, led by academic researchers and funded by the US National Institutes of Health and Pfizer, represents an important university industry collaboration: newer drugs were compared with an established drug instead of a placebo for clinically important outcomes. Diuretics should be the standard reference group in future comparative trials.

The superiority of low dose diuretics is not likely to be promoted by industry. Indeed, “opinion leaders” argue that BP control is inadequate; everyone needs 2 drugs, so combination therapy should be first line therapy.¹ During ALLHAT, which used the traditional stepped care approach, 40–60% of patients were taking only 1 drug. For the large proportion of patients with hypertension whose BP can be controlled on 1 drug, the 2 drugs for everyone approach, which remains largely untested, would unnecessarily expose many patients to adverse effects without known benefit.