ALLHAT-LLT: questions, questions, and more questions (and some answers).

The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial--Lipid Lowering Trial (ALLHAT-LLT) compared 40 mg/d of pravastatin with usual care among 10,355 men and women aged 55 years or older with stage 1 or 2 hypertension, at least one additional coronary heart disease risk factor, and low-density lipoprotein (LDL) cholesterol levels of 120 to 189 mg/dL. After a mean of 4.8 years of treatment and follow-up, the difference in total cholesterol between the two arms was 9.6%, whereas in a small, nonrandomized subsample, the LDL cholesterol differential was 16.7%. No differences were observed between the pravastatin and usual-care groups with respect to all-cause mortality, cardiovascular deaths, noncardiovascular deaths, and a composite endpoint of fatal coronary heart disease plus nonfatal myocardial infarction. Despite these null findings, the results of ALLHAT-LLT are not inconsistent with previous trials because of the very small lipid differences in the two arms. This indirectly supports the hypothesis that LDL cholesterol lowering is central to the cardiovascular benefits associated with statin therapy, with greater clinical impacts observed when there are greater differences between treatment and control arms. ALLHAT-LLT underscores the difficulty of conducting an open-label trial in an era of rapidly changing professional and public understanding of the possible benefits of lipid-lowering therapy and highlights the substantial gap between actual care in clinical practice and optimal care based on the best knowledge from randomized clinical trials.