Estimating the effect of pravastatin vs usual care under full adherence in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial-Lipid Lowering Trial.

The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack-Lipid-Lowering Trial (ALLHAT-LLT) was a pragmatic randomized trial conducted in 513 clinical centers across North America from 1994 to 2002. ALLHAT-LLT, which used standard of care (usual care) as the control treatment, did not find an effect of assignment to pravastatin on all-cause death. We aimed to use the trial data to estimate the effect of adhering to the assigned treatment, that is, the per-protocol effect. Moderately hypercholesterolemic (low-density lipoprotein cholesterol 100-189 mg/dL), hypertensive participants ≥55 years old were included and randomized to pravastatin (40 mg/day unless contraindicated) or usual care (lipid-lowering treatment discouraged unless clinically indicated). Of 10 355 individuals randomized, we included 9741 with complete baseline data. One-third of individuals in the pravastatin arm were non-adherent to the assigned treatment strategy at year 5. After adjusting for factors related to adherence, the 5 year risk difference comparing pravastatin to usual care was -3.0% (-4.9%, -1.3%), and the risk ratio was 0.79 (0.68, 0.91) for death. Findings were consistent across different definitions of treatment strategies. Our results suggest that the use of pravastatin under full adherence was protective against death, even if assignment to pravastatin was not clearly protective.