Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT): practical implications.

Rationale The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), sponsored by the National Heart, Lung, and Blood Institute (NHLBI), is the largest outcome trial of antihypertensive treatment ever carried out and the only large blood pressure (BP) trial to be carried out in a US population in the past decade.1 The rationale for ALLHAT, which was designed in the early 1990s, was the urgent need to determine which of the several classes of antihypertensive drugs that had been developed and released for clinical use was most effective in preventing coronary heart disease (CHD), defined as fatal CHD and nonfatal myocardial infarction.2 The only randomized trials that had previously compared representatives of the antihypertensive drug classes, the Department of Veterans Affairs Cooperative Study Group on Antihypertensive Agents3 and the Treatment of Mild Hypertension Study (TOMHS),4 showed BP reductions with all classes but were not powered to evaluate CHD outcomes. Further, prior outcome trials had shown that the reduction in CHD event rates with antihypertensive treatment was less than expected based on epidemiologic data.5 Adverse effects of study drugs, particularly diuretics, including hypokalemia, hypomagnesemia, hyperuricemia, hyperlipidemia, insulin resistance, and ventricular ectopic activity, had been adduced to account for the disappointing outcomes of earlier trials by offsetting the beneficial effects of BP reduction.6,7 To further complicate the picture, benefits beyond BP reduction had been attributed to some antihypertensive drug classes, ie, improved survival and reduced morbidity in persons with heart failure or left ventricular dysfunction treated with angiotensin-converting enzyme (ACE) inhibitors8–10 and improved insulin sensitivity and lipid profiles with a-blocker treatment.11 In contrast, another antihypertensive drug class, the dihydropyridine calcium channel blockers (CCBs), had been associated with unfavorable outcomes in patients with acute myocardial infarction or unstable angina.12 There were no data comparing the effectiveness of different classes of antihypertensive drugs in preventing cardiovascular disease (CVD) outcomes and no outcome data at all on the effectiveness of antihypertensive treatment in high-risk populations, including blacks and persons with type 2 diabetes. A final issue was the rapidly rising cost of treating hypertension in the US, a cost that was driven, in part, by increased acquisition prices of the newer classes of drugs compared with the older diuretics, the only class that had been shown to reduce CVD outcomes.