The ALLHAT Lipid Lowering Trial—Less Is Less

The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial Lipid Lowering Trial (ALLHAT-LLT),¹ published in this issue of THE JOURNAL, is the second-largest lipid-lowering trial yet reported. This randomized trial, a subset of the larger ALLHAT hypertension study,² followed up 10 355 patients (49% women) who had hypertension and were 55 years or older for a mean of 4.8 years. Patients were randomly assigned to receive 40 mg of pravastatin (open label) vs "usual care" in 513 clinical centers, the majority of which were community-based. These centers were a subset of the 623 centers that treated patients for the larger (N = 33 357) ALLHAT hypertension study.² Despite a 28% reduction in low-density lipoprotein cholesterol (LDL-C) from baseline in the pravastatin treatment group, the trial failed to show a benefit in either the primary outcome (all-cause mortality) or the key secondary outcome (combined nonfatal myocardial infarction and fatal coronary heart disease).¹ How can this be? Why didn't ALLHAT-LLT work?