Effect of statin use for the primary prevention of cardiovascular disease among older adults: A cautionary tale concerning target trials emulation.

OBJECTIVE: Evidence concerning the effect of statins in primary prevention of cardiovascular disease (CVD) among older adults is lacking. Using Quebec population-wide administrative data, we emulated a hypothetical randomized trial including older adults >65 years on April 1st, 2013, with no CVD history and no statin use in the previous year.

STUDY DESIGN AND SETTING: We included individuals who initiated statins and classified them as exposed if they were using statin at least three months after initiation and non-exposed otherwise. We followed them until March 31, 2018. The primary outcome was the composite endpoint of coronary events (myocardial infarction, coronary bypass, percutaneous coronary intervention), stroke, and all-cause mortality. The intention-to-treat (ITT) effect was estimated with adjusted Cox models, and per-protocol effect with inverse probability of censoring weighting.

RESULTS: A total of 65,096 individuals were included (mean age = 71.0±5.5, female = 55.0%) and 93.7% were exposed. While we observed a reduction in the composite outcome (ITT-HR = 0.75; 95%CI : 0.68-0.83) and mortality (ITT-HR = 0.69; 95%CI : 0.61-0.77) among exposed, coronary events increased (ITT-HR = 1.46; 95%CI : 1.09-1.94). All multi-bias E-values were low indicating that the results were not robust to unmeasured confounding, selection, and misclassification biases simultaneously.

CONCLUSIONS: We cannot conclude on the effectiveness of statins in primary prevention of CVD among older adults. We caution that an in-depth reflection on sources of biases and careful interpretation of results are always required in observational studies.