Context Studies have demonstrated that statins administered to individuals with
risk factors for coronary heart disease (CHD) reduce CHD events. However,
many of these studies were too small to assess all-cause mortality or outcomes
in important subgroups.
Objective To determine whether pravastatin compared with usual care reduces all-cause
mortality in older, moderately hypercholesterolemic, hypertensive participants
with at least 1 additional CHD risk factor.
Design and Setting Multicenter (513 primarily community-based North American clinical centers),
randomized, nonblinded trial conducted from 1994 through March 2002 in a subset
of participants from the Antihypertensive and Lipid-Lowering Treatment to
Prevent Heart Attack Trial (ALLHAT).
Participants Ambulatory persons (n = 10 355), aged 55 years or older, with low-density
lipoprotein cholesterol (LDL-C) of 120 to 189 mg/dL (100 to 129 mg/dL if known
CHD) and triglycerides lower than 350 mg/dL, were randomized to pravastatin
(n = 5170) or to usual care (n = 5185). Baseline mean total cholesterol was
224 mg/dL; LDL-C, 146 mg/dL; high-density lipoprotein cholesterol, 48 mg/dL;
and triglycerides, 152 mg/dL. Mean age was 66 years, 49% were women, 38% black
and 23% Hispanic, 14% had a history of CHD, and 35% had type 2 diabetes.
Intervention Pravastatin, 40 mg/d, vs usual care.
Main Outcome Measures The primary outcome was all-cause mortality, with follow-up for up to
8 years. Secondary outcomes included nonfatal myocardial infarction or fatal
CHD (CHD events) combined, cause-specific mortality, and cancer.
Results Mean follow-up was 4.8 years. During the trial, 32% of usual care participants
with and 29% without CHD started taking lipid-lowering drugs. At year 4, total
cholesterol levels were reduced by 17% with pravastatin vs 8% with usual care;
among the random sample who had LDL-C levels assessed, levels were reduced
by 28% with pravastatin vs 11% with usual care. All-cause mortality was similar
for the 2 groups (relative risk [RR], 0.99; 95% confidence interval [CI],
0.89-1.11; P = .88), with 6-year mortality rates
of 14.9% for pravastatin vs 15.3% with usual care. CHD event rates were not
significantly different between the groups (RR, 0.91; 95% CI, 0.79-1.04; P = .16), with 6-year CHD event rates of 9.3% for pravastatin
and 10.4% for usual care.
Conclusions Pravastatin did not reduce either all-cause mortality or CHD significantly
when compared with usual care in older participants with well-controlled hypertension
and moderately elevated LDL-C. The results may be due to the modest differential
in total cholesterol (9.6%) and LDL-C (16.7%) between pravastatin and usual
care compared with prior statin trials supporting cardiovascular disease prevention.