Clinical study of the month. Which initial antihypertensive? Results from the ALLHAT trial

peer reviewedAntihypertensive therapy is well established to reduce hypertension-related morbidity and mortality, but the optimal first-step therapy is still controversial. The "Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial" (ALLHAT) should give such an answer. It is a randomised, double-blind, trial designed to determine whether treatment with either a calcium channel blocker or an angiotensin-converting enzyme inhibitor lowers the incidence of coronary heart disease (CHD) or other cardiovascular disease (CVD) events vs treatment with a diuretic. A total of 33,357 participants aged 55 years or older with mild to moderate hypertension and at least 1 other CHD risk factor were randomly assigned to receive chlorthalidone (12.5 to 25 mg/day; n = 15,255), amlodipine (2.5 to 10 mg/day; n = 9,048) or lisinopril (10 to 40 mg; n = 9,054). The primary outcome combined both fatal CHD and non-fatal myocardial infarction, analyzed by intent-to-treat. Secondary outcomes were all-causes mortality, stroke, combined CHD (primary outcome, coronary revascularization, or angina with hospitalization), and combined CVD (combined CHD, stroke, treated angina without hospitalization, heart failure and peripheral arterial disease). Chlorthalidone was slightly more effective in reducing systolic pressure while amlodipine reduced slightly more effectively diastolic blood pressure. After a mean follow up of 4.9 years, no differences were observed between the three treatments regarding both the primary outcome and the total mortality. Secondary outcomes were similar when comparing amlodipine vs chlorthalidone. A moderately higher 6-year incidence rate of clinically detected heart failure was observed with amlodipine, but without significant influence on mortality. For lisinopril vs chlorthalidone, lisinopril had slightly higher 6-year rates of combined CVD, stroke and heart failure. In conclusion, thiazide-type diuretics are superior in preventing one or more major forms of CVD and offer the advantage to be cheaper. They should be preferred for first-step antihypertensive therapy. However, to reach the recommended blood pressure target, most patients should receive a combination of antihypertensive compounds. Such a combination should always comprise a diuretic agent, in absence of contra-indications