Evaluation of Time to Benefit of Statins for the Primary Prevention of Cardiovascular Events in Adults Aged 50 to 75 Years A Meta-analysis

Question What is the time to benefit of statin therapy for primary prevention of cardiovascular events in adults aged 50 to 75 years? Findings In this survival meta-analysis of 8 trials randomizing 65 383 adults, 2.5 (95% CI, 1.7-3.4) years were needed to avoid 1 cardiovascular event for 100 patients treated with a statin. Meaning These findings suggest that statin medications for the primary prevention of cardiovascular events may reduce cardiac events for some adults aged 50 to 75 years with a life expectancy of at least 2.5 years; no data suggest a mortality benefit. Importance Guidelines recommend targeting preventive interventions toward older adults whose life expectancy is greater than the intervention's time to benefit (TTB). The TTB for statin therapy is unknown. Objective To conduct a survival meta-analysis of randomized clinical trials of statins to determine the TTB for prevention of a first major adverse cardiovascular event (MACE) in adults aged 50 to 75 years. Data Sources Studies were identified from previously published systematic reviews (Cochrane Database of Systematic Reviews and US Preventive Services Task Force) and a search of MEDLINE and Google Scholar for subsequently published studies until February 1, 2020. Study Selection Randomized clinical trials of statins for primary prevention focusing on older adults (mean age >55 years). Data Extraction and Synthesis Two authors independently abstracted survival data for the control and intervention groups. Weibull survival curves were fit, and a random-effects model was used to estimate pooled absolute risk reductions (ARRs) between control and intervention groups each year. Markov chain Monte Carlo methods were applied to determine time to ARR thresholds. Main Outcomes and Measures The primary outcome was time to ARR thresholds (0.002, 0.005, and 0.010) for a first MACE, as defined by each trial. There were broad similarities in the definition of MACE across trials, with all trials including myocardial infarction and cardiovascular mortality. Results Eight trials randomizing 65 383 adults (66.3% men) were identified. The mean age ranged from 55 to 69 years old and the mean length of follow-up ranged from 2 to 6 years. Only 1 of 8 studies showed that statins decreased all-cause mortality. The meta-analysis results suggested that 2.5 (95% CI, 1.7-3.4) years were needed to avoid 1 MACE for 100 patients treated with a statin. To prevent 1 MACE for 200 patients treated (ARR = 0.005), the TTB was 1.3 (95% CI, 1.0-1.7) years, whereas the TTB to avoid 1 MACE for 500 patients treated (ARR = 0.002) was 0.8 (95% CI, 0.5-1.0) years. Conclusions and Relevance These findings suggest that treating 100 adults (aged 50-75 years) without known cardiovascular disease with a statin for 2.5 years prevented 1 MACE in 1 adult. Statins may help to prevent a first MACE in adults aged 50 to 75 years old if they have a life expectancy of at least 2.5 years. There is no evidence of a mortality benefit. This meta-analysis assesses randomized clinical trials of statins to determine the time to benefit for prevention of a first major adverse cardiovascular event in adults aged 50 to 75 years.