What ALLHAT tells us about treating high-risk patients with hypertension and hyperlipidemia

Hypertension and hyperlipidemia are potent cardiovascular risk factors. Treatment can lower blood pressure and reduce events, but the optimal drug for initial hypertension treatment and the benefits of long-term cholesterol reduction on clinical outcomes in understudied hypertensive subpopulations were unknown. The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) was a long-term randomized, multicenter study undertaken to address these questions. In the hypertension component, 42,448 patients with mild-moderate hypertension and 1 or more other coronary risk factors were randomized to initial therapy with chlorthalidone, or to a newer antihypertensive agent--doxazosin (alpha blocker), amlodipine (calcium blocker), or lisinopril (angiotensin-converting enzyme inhibitor). The primary combined endpoint was coronary heart disease mortality or nonfatal myocardial infarction, with secondary endpoints including combinations of mortality, cardiac, and vascular complications. By interim analysis, doxazosin was shown inferior to diuretics in preventing secondary endpoints, resulting in early termination of this arm. There were no differences in primary endpoint frequency in chlorthalidone-amlodipine and chlorthalidone-lisinopril comparisons, but both amlodipine and lisinopril therapy resulted in more secondary events. In the lipid-lowering trial, 10,355 patients enrolled in the hypertensive trial with low-density-lipoprotein levels 100 to 189 mg/dL were randomized to pravastatin or usual care. There was no overall difference in the primary endpoint (total mortality) or most secondary endpoints, with statin therapy reducing stroke and coronary events modestly but nonsignificantly. Subgroup comparisons showed equivalent treatment effects in all groups except blacks, who had greater reduction in total coronary events but more strokes with pravastatin therapy and more strokes with lisinopril treatment.