Abstract
Introduction: In the ODYSSEY OUTCOMES trial, alirocumab improved cardiovascular outcomes and reduced death after acute coronary syndrome (ACS). Median follow-up was 2.8 yrs (range 2-5). The effects of alirocumab on long-term survival are unknown. Objective: To calculate projected life span and potential survival gains with alirocumab vs placebo after ACS using validated nonparametric age-based methods. Methods: In ODYSSEY OUTCOMES (NCT01663402), 18,924 patients with recent ACS and elevated atherogenic lipoproteins despite high-intensity or maximum-tolerated statin therapy were randomized to alirocumab or placebo. All-cause death was a secondary trial outcome. Age-based estimates of projected survival and event-free (all-cause death, nonfatal myocardial infarction, nonfatal ischemic stroke) survival were calculated. In each treatment arm at every year of age, lifespan was estimated from area under the survival curve, to a maximum of 85 yrs. Differences in areas under the survival curves provide an estimate of the benefit of alirocumab on survival. Results: Mean (SD) baseline age was 58.5 (9.3) yrs. Mean survival benefits with alirocumab vs placebo ranged from 0.03 to 1.62 yrs, decreasing with age and becoming neutral at age 80-85 yrs. For example, at age 40, estimated survival was another 37.5 yrs with alirocumab and 35.9 yrs with placebo (difference 1.62 yrs [95% CI, 0.30-2.94]; P =0.016). At age 60, it was 20.5 vs 19.6 yrs (difference 0.88 [95% CI, 0.16-1.61]; P =0.017); at age 75 it was 8.8 vs 8.3 (difference 0.57 [0.09-1.05]; P =0.019); and at age 80, it was 4.5 vs 4.5 years (difference 0.03 [-0.28 to 0.35]; P =0.83). Mean event-free survival benefit similarly ranged from 1.85 to 0.0 yrs. Conclusions: Modeling suggests that long-term treatment with alirocumab may result in a meaningful increase in survival among patients less than 80 yrs of age. This analysis may facilitate shared decision-making with patients. Funding: Sanofi, Regeneron Pharmaceuticals
Published Version
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