Amlodipine and lisinopril were associated with higher risks of hospitalized or fatal heart failure compared to chlorthalidone (RR 1.35, P<0.001 and RR 1.11, P=0.09, respectively).
RCT (n=33,357)
Double-blind
Does chlorthalidone reduce hospitalized or fatal heart failure compared to amlodipine or lisinopril in high-risk hypertensive patients aged >=55 years?
Chlorthalidone is superior to amlodipine and lisinopril in preventing heart failure in high-risk hypertensive patients, particularly during the first year of treatment.
Effect estimate: RR 1.35 (95% CI 1.21 to 1.50)
p-value: p=<0.001
BACKGROUND: Hypertension is a major cause of heart failure (HF) and is antecedent in 91% of cases. The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) stipulated assessment of the relative effect of chlorthalidone, lisinopril, and amlodipine in preventing HF. METHODS AND RESULTS: ALLHAT was a double-blind, randomized, clinical trial in 33,357 high-risk hypertensive patients aged > or =55 years. Hospitalized/fatal HF outcomes were examined with proportional-hazards models. Relative risks (95% confidence intervals; P values) of amlodipine or lisinopril versus chlorthalidone were 1.35 (1.21 to 1.50; <0.001) and 1.11 (0.99 to 1.24; 0.09). The proportional hazards assumption of constant relative risk over time was not valid. A more appropriate model showed relative risks of amlodipine or lisinopril versus chlorthalidone during year 1 were 2.22 (1.69 to 2.91; <0.001) and 2.08 (1.58 to 2.74; <0.001), and after year 1, 1.22 (1.08 to 1.38; P=0.001) and 0.96 (0.85 to 1.10; 0.58). There was no significant interaction between prior medication use and treatment. Baseline blood pressures were equivalent (146/84 mm Hg) and at year 1 were 137/79, 139/79, and 140/80 mm Hg in those given chlorthalidone, amlodipine, and lisinopril. At 1 year, use of added open-label atenolol, diuretics, angiotensin-converting enzyme inhibitors, and calcium channel blockers in the treatment groups was similar. CONCLUSIONS: HF risk decreased with chlorthalidone versus amlodipine or lisinopril use during year 1. Subsequently, risk for those individuals taking chlorthalidone versus amlodipine remained decreased but less so, whereas it was equivalent to those given lisinopril. Prior medication use, follow-up blood pressures, and concomitant medications are unlikely to explain most of the HF differences. Diuretics are superior to calcium channel blockers and, at least in the short term, angiotensin-converting enzyme inhibitors in preventing HF in hypertensive individuals.
Davis et al. (Tue,) conducted a rct in Hypertension (n=33,357). Amlodipine or lisinopril vs. Chlorthalidone was evaluated on Hospitalized/fatal heart failure (RR 1.35, 95% CI 1.21 to 1.50, p=<0.001). Amlodipine and lisinopril were associated with higher risks of hospitalized or fatal heart failure compared to chlorthalidone (RR 1.35, P<0.001 and RR 1.11, P=0.09, respectively).