Effect of P2Y12 Inhibitors on Major Adverse Cardiovascular Events After Coronary Artery Bypass Graft Surgery: A Population‐Based Cohort Study

BACKGROUND: Patients who undergo coronary artery bypass graft (CABG) surgery remain at high risk for major adverse cardiovascular events (MACE) despite contemporary preventive pharmacotherapy. Although commonly used in practice, it is uncertain whether P2Y12 inhibitors reduce MACE in patients post-CABG surgery. METHODS: This retrospective, population-based cohort study evaluated the effect of exposure to P2Y12 inhibitors, versus no exposure, on MACE using linked administrative databases that included all cardiac revascularization procedures, hospitalizations, and prescriptions for the population of British Columbia, Canada. All adults who underwent CABG surgery from 2002 to 2020 were eligible. The primary outcome was time to MACE, defined as a composite of all-cause death, nonfatal myocardial infarction, and nonfatal ischemic stroke using Cox proportional hazards models with inverse probability treatment weighting. RESULTS: Included were 15,439 patients. Mean age was 66 years, and 83% were male. Fifty-seven percent had a previous myocardial infarction. Sixteen percent were prescribed a P2Y12 inhibitor (of which, 83% were prescribed clopidogrel) within 30 days of CABG surgery. Median exposure time was 23 months. After probability-weighting and adjustment for relevant covariates, exposure to P2Y12 inhibitors reduced the 1- and 5-year hazard of MACE (hazard ratio HR 0.39, 95% confidence interval CI 0.27-0.55 and HR 0.65, 95% CI 0.54-0.79, respectively). Exposure to P2Y12 inhibitors was also associated with a lower hazard of all-cause death, cardiovascular death, and an extended MACE outcome that included unstable angina and percutaneous coronary intervention. Adherence to P2Y12 inhibitor therapy, based on the proportion of days covered, did not affect these outcomes. CONCLUSIONS: In this population-based cohort study, use of P2Y12 inhibitors reduced the hazard of MACE in patients post-CABG surgery at 1 and 5 years of follow-up. These results support the use of P2Y12 inhibitors (primarily clopidogrel), in addition to other standard cardiovascular preventive therapy, in patients who undergo CABG surgery.