Neither amlodipine (HR 1.00; 95% CI 0.93-1.06) nor lisinopril (HR 0.97; 95% CI 0.90-1.03) was superior to chlorthalidone for long-term prevention of cardiovascular mortality.
RCT (n=32,804)
Double-blind
Randomized
Yes
Do amlodipine or lisinopril reduce cardiovascular mortality compared to chlorthalidone in participants aged 55 years and older with hypertension and ≥ 1 other coronary heart disease risk factors?
Long-term follow-up of the ALLHAT trial confirms that neither calcium channel blockers nor ACE inhibitors are superior to thiazide-type diuretics for preventing major cardiovascular complications of hypertension.
Effect estimate: HR 1.00 (amlodipine); HR 0.97 (lisinopril) (95% CI 0.93-1.06 (amlodipine); 0.90-1.03 (lisinopril))
p-value: p=>0.05
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.
Cushman et al. (Fri,) conducted a rct in Hypertension (n=32,804). Amlodipine or lisinopril vs. Chlorthalidone was evaluated on Cardiovascular mortality (HR 1.00 (amlodipine); HR 0.97 (lisinopril), 95% CI 0.93-1.06 (amlodipine); 0.90-1.03 (lisinopril), p=>0.05). Neither amlodipine (HR 1.00; 95% CI 0.93-1.06) nor lisinopril (HR 0.97; 95% CI 0.90-1.03) was superior to chlorthalidone for long-term prevention of cardiovascular mortality.