Coronary heart disease in moderately hypercholesterolemic, hypertensive black and non-black patients randomized to pravastatin versus usual care: the antihypertensive and lipid lowering to prevent heart attack trial (ALLHAT-LLT).

BACKGROUND: In previous analyses in ALLHAT, blacks had a significantly lower risk of coronary heart disease (CHD) in the pravastatin group compared to the usual care group, whereas non-blacks had no benefit from pravastatin. No previous statin trial has reported results separately in blacks. OBJECTIVES: The study aimed to determine if apparent racial differences in CHD in ALLHAT are explained by differences in baseline characteristics, adherence during the trial, or achieved blood pressure and lipid lowering. METHODS: This was a prespecified subgroup analysis of a randomized controlled trial. Hypertensive, moderately hypercholesterolemic participants were assigned to open-label pravastatin (40 mg/d) or usual care. The outcome was a composite of nonfatal myocardial infarction and fatal CHD. We performed intention-to-treat survival analyses using Cox proportional hazards models, adjusting for baseline covariates (age, sex, aspirin use, history of CHD and diabetes, and baseline hypertension treatment) and time-varying levels of blood pressure and total cholesterol. RESULTS: After adjustment for baseline characteristics, there remained a significant interaction between race and treatment group (P = .02). In stratified models, blacks in the pravastatin group had a 29% lower risk of CHD (hazard ratio [HR] 0.71, 95% CI 0.57-0.90, P = .005) compared to those in the usual care group, whereas non-blacks had no benefit (HR 1.00, 95% CI 0.85-1.19, P = .95). With further adjustment for achieved blood pressure and total cholesterol, the HR in blacks was 0.65 (95% CI 0.45-0.96, P = .03) and in non-blacks was 1.07 (95% CI 0.81-1.41, P = .65). CONCLUSIONS: Our results suggest that pravastatin is effective in preventing CHD in blacks.

Role of diuretics in the prevention of heart failure: the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial.

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.