Studies of statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) have shown that these cholesterol-lowering drugs reduce coronary heart disease (CHD) events when administered to patients with risk factors for CHD. The purpose of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial–Lipid-Lowering Trial (ALLHAT–LLT) was to assess the effect of pravastatin on all-cause mortality in hypertensive patients with at least one other cardiovascular risk factor, emphasizing a primary care setting that includes a diverse population.
ALLHAT participants were enrolled in the LLT arm of the study if they had a fasting low-density lipoprotein (LDL) cholesterol level of 120 to 189 mg per dL (3.1 to 4.9 mmol per L) with no known CHD or 100 to 129 mg per dL (2.6 to 3.3 mmol per L) in those with known CHD, and fasting triglyceride levels of less than 350 mg per dL (3.9 mmol per L). More than 10,000 patients in the ALLHAT–LLT study were randomized to treatment with open-label pravastatin or usual care in a 1:1 ratio. Usual-care patients were treated to lower their LDL levels according to the discretion of the primary care physician, but aggressive lipid-lowering therapy was discouraged.
Follow-up took place at three, six, nine, and 12 months, and every four months thereafter. The primary outcome was all-cause mortality, with composite fatal or nonfatal myocardial infarction (MI), cause-specific mortality, total and site-specific cancers, Q-wave MI by electrocardiography, health-related quality of life, and major medical cost as secondary outcomes.
Mean follow-up was 4.8 years. After four years of follow-up, total cholesterol levels decreased by 17.2 percent in the pravastatin group and by 7.6 percent in the usual-care group, with LDL levels decreasing by 27.7 and 11.0 percent, respectively. There was no significant difference in all-cause mortality between the pravastatin group and the usual-care group, with six-year mortality rates of 14.9 and 15.3 percent, respectively. Rates of CHD and stroke were somewhat lower in the pravastatin group than in the usual-care group. Of note, in subgroup analysis, pravastatin showed a significantly more favorable effect on CHD events in blacks than in non-blacks, with a significantly less favorable effect in blacks for stroke.
The ALLHAT–LLT supports the conclusion that, in a diverse population with adherence rates similar to those of other trials, pravastatin does not contribute to a statistically significant reduction in all-cause mortality when compared with usual care. The investigators attribute this finding in part to the small difference in total cholesterol levels between the two groups, both of which achieved reductions in cholesterol levels. They interpret the results as an invitation to aggressive cholesterol-lowering, because the efficacy of this treatment has been well established in other trials.