Pravastatin for Primary Prevention in Older Adults: Restricted Mean Survival Time Analysis

Objectives: To use restricted mean survival time, which summarizes treatment effects in terms of event-free time over a fixed time period, to evaluate the benefit of pravastatin therapy for primary prevention of cardiovascular disease in older adults. Design: Secondary analysis of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial-Lipid-Lowering Trial (ALLHAT-LLT). Setting: Ambulatory setting. Participants: Individuals aged 65 and older (mean aged 71, 49% female) free of cardiovascular disease (N=2,867). Intervention: Pravastatin 40 mg/d (n=1,467) versus usual care (n=1,400). Measurements: We estimated the difference in RMST for total and coronary heart disease (CHD)-free survival between the pravastatin and usual care groups over the 6-year trial period and used parametric survival models to estimate RMST differences projected over 10 years. Results: Over 6 years, individuals treated with pravastatin lived (RMST 2,008.1 days), on average, 33.7 fewer days than those receiving usual care (RMST 2,041.8 days) (difference –33.7 days, 95% confidence interval (CI)=–67.0 to –0.5 days, p=.047). Pravastatin-treated individuals lived RMST 2,088.1 days), on average, 18.7 more days free of CHD over 6 years than those receiving usual care (RMST 2,069.4 days), but this difference was not statistically significant (difference 18.7 days, 95% CI=–10.4–47.8 days, p=.21). The 10-year projection showed that pravastatin-treated individuals would live 108.1 fewer days (95% CI=–204.5 to –14.1, p=.03) than those receiving usual care, although treated individuals would gain 77.9 days (95% CI=3.8–159.6, p=.046) of CHD-free survival. Conclusion: RMST provides an intuitive and explicit way to express the effect of pravastatin therapy on CHD-free and overall survival in older adults free of cardiovascular disease. This measure allows a more personalized interpretation than hazard ratios of the benefits and risks of a medical intervention for decision-making.