The Antihypertensive and Lipid-Lowering treatment to prevent Heart Attack Trial (ALLHAT) is the largest trial of blood pressure–lowering therapy to date (20). This trial compared the effectiveness of an ACE inhibitor (lisinopril) versus a calcium-channel blocker (amlodipine) versus a thiazide diuretic (chlorthalidone) as first-line therapy for mild to moderate hypertension. The primary outcome was combined fatal coronary heart disease or nonfatal myocardial infarction. Secondary outcomes were all-cause mortality, stroke, combined coronary heart disease (primary outcome, coronary revascularization, or angina with hospitalization), and combined cardiovascular disease (combined coronary heart disease, stroke, treated angina without hospitalization, heart failure, and peripheral arterial disease). The results showed no differences between treatments in primary outcome or all-cause mortality. The amlodipine group had a higher risk for heart failure than the chlorthalidone group. Cholesterol levels, prevalence of hypokalemia, and incidence of new diabetes were higher in the chlorthalidone group than in the other groups after 2 and 4 years of follow-up. However, these differences did not translate into increased cardiovascular events or higher mortality rates. For the diabetic patients, lisinopril appeared to have no special advantage over chlorthalidone for most cardiovascular and renal outcomes. Moreover, in self-reported black patients, lisinopril was less effective than chlorthalidone in reducing combined cardiovascular end points and stroke and showed a similar trend for heart failure and poorer blood pressure lowering. It should also be noted that on average, 40% of patients required more than one drug; the average number of drugs per patient was two. In addition, one third of patients did not reach the goal blood pressure of 140/90 mm Hg or less.