RATIONALE AND DESIGN FOR THE ANTIHYPERTENSIVE AND LIPID-LOWERING TREATMENT TO PREVENT HEART-ATTACK TRIAL (ALLHAT)

Are newer types of antihypertensive agents, which are currently more c ostly to purchase on average, as good or better than diuretics in redu cing coronary heart disease incidence and progression? Will lowering L DL cholesterol in moderately hypercholesterolemic older individuals re duce the incidence of cardiovascular disease and total mortality? Thes e important medical practice and public health questions are to be add ressed by the Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), a randomized, double-blind trial in 40,0 00 high-risk hypertensive patients. ALLHAT is designed to determine wh ether the combined incidence of fatal coronary heart disease (CHD) and nonfatal myocardial infarction differs between persons randomized to diuretic (chlorthalidone) treatment and each of three alternative trea tments-a calcium antagonist (amlodipine), an angiotensin converting en zyme inhibitor (lisinopril), and an Lu-adrenergic blocker (doxazosin). ALLHAT also contains a randomized, open-label, lipid-lowering trial d esigned to determine whether lowering LDL cholesterol in 20,000 modera tely hypercholesterolemic patients (a subset of the 40,000) with a 3-h ydroxymethylglutaryl coenzyme A (HMG CoA) reductase inhibitor, pravast atin, will reduce all-cause mortality compared to a control group rece iving ''usual care.'' ALLHAT's main eligibility criteria are: 1) age 5 5 or older; 2) systolic or diastolic hypertension; and 3) one or more additional risk factors for heart attack leg, evidence of atherosclero tic disease or type II diabetes). For the lipid-lowering trial, partic ipants must have an LDL cholesterol of 120 to 189 mg/dL (100 to 129 mg /dL for those with known CHD) and a triglyceride level below 350 mg/dL . The mean duration of treatment and follow-up is planned to be 6 year s. Further features of the rationale, design, objectives, treatment pr ogram, and study organization of ALLHAT are described in this article.