Mortality and Morbidity During and After the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial


Sara L. Pressel, MS, ALLHAT Clinical Trials Center, University of Texas School of Public Health, RAS W908, University of Texas Health Science Center at Houston, 1200 Herman Pressler Drive, Houston, TX 77030


A randomized, double-blind, active-controlled, multicenter trial assigned 32,804 participants aged 55 years and older with hypertension and ≥1 other coronary heart disease risk factors to receive chlorthalidone (n=15,002), amlodipine (n=8898), or lisinopril (n=8904) for 4 to 8 years, when double-blinded therapy was discontinued. Passive surveillance continued for a total follow-up of 8 to 13 years using national administrative databases to ascertain deaths and hospitalizations. During the post-trial period, fatal outcomes and nonfatal outcomes were available for 98% and 65% of participants, respectively, due to lack of access to administrative databases for the remainder. This paper assesses whether mortality and morbidity differences persisted or new differences developed during the extended follow-up. Primary outcome was cardiovascular mortality and secondary outcomes were mortality, stroke, coronary heart disease, heart failure, cardiovascular disease, and end-stage renal disease. For the post-trial period, data are not available on medications or blood pressure levels. No significant differences (P<.05) appeared in cardiovascular mortality for amlodipine (hazard ratio [HR], 1.00; 95% confidence interval [CI], 0.93–1.06) or lisinopril (HR, 0.97; CI, 0.90–1.03), each compared with chlorthalidone. The only significant differences in secondary outcomes were for heart failure, which was higher with amlodipine (HR, 1.12; CI, 1.02–1.22), and stroke mortality, which was higher with lisinopril (HR, 1.20; CI, 1.01–1.41), each compared with chlorthalidone. Similar to the previously reported in-trial result, there was a significant treatment-by-race interaction for cardiovascular disease for lisinopril vs chlorthalidone. Black participants had higher risk than non-black participants taking lisinopril compared with chlorthalidone. After accounting for multiple comparisons, none of these results were significant. These findings suggest that neither calcium channel blockers nor angiotensin-converting enzyme inhibitors are superior to diuretics for the long-term prevention of major cardiovascular complications of hypertension.