The ALLHAT-LLT and ASCOT-LLA trials: are the discrepancies more apparent than real?

During the past decade, numerous landmark trials of statins in secondary and primary prevention and their meta-analyses have demonstrated statistically significant and clinically important reductions in myocardial infarction, stroke, and vascular death (by about one third), as well as total mortality (by about one fifth). In the past year, two trials of statins have been reported among hypertensive subjects enrolled in blood pressure-lowering trials, one in the United States and the other in Europe. The US trial, the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial--Lipid Lowering Trial (ALLHAT-LLT), was reported as showing no significant benefit. In contrast, the European trial, the Anglo-Scandinavian Cardiac Outcomes Trial--Lipid Lowering Arm (ASCOT-LLA), was terminated early based on the unanimous recommendation of the Data and Safety Monitoring Board, due principally to the emergence of a statistically extreme 36% reduction in the primary endpoint of nonfatal myocardial infarction and death from coronary heart disease (P<0.0005). These trial results have been viewed as discrepant, but methodologic issues of inadequate power of ALLHAT due to lower than projected sample size and poor compliance due to an open design render these discrepancies more apparent than real. The ALLHAT-LLT trial should be viewed not as null, but as uninformative, as the 95% confidence limits around the point estimate include the most plausible small to moderate benefit of statins. The totality of evidence on statins continues to strongly support their benefits in a wide range of patients on a large number of cardiovascular disease endpoints.