(001) Association of ticagrelor versus clopidogrel with major adverse cardiovascular events in patients with acute coronary syndrome undergoing percutaneous coronary intervention across categories of liver disease
PhD Candidate School of Pharmacy, Sungkyunkwan University, Suwon, South Korea, Republic of Korea
Background: Unlike direct-acting agent ticagrelor, clopidogrel is a prodrug that requires conversion into its active metabolite in the liver, a process that may be influenced by decreased activity of CYP2C19 caused by liver impairment. However, the effectiveness and safety evidence of ticagrelor vs clopidogrel in patients with chronic liver disease (CLD) are scarce.
Objectives: To assess the effectiveness and safety of ticagrelor versus clopidogrel in patients undergoing percutaneous coronary intervention (PCI) due to acute coronary syndrome (ACS) by CLD status.
Methods: Using the nationwide healthcare database of South Korea from 2011 to 2020, we included patients aged ≥ 18 years who underwent PCI and initiated ticagrelor or clopidogrel within 7 days of ACS diagnosis. Patients were divided into two mutually exclusive groups: patients with CLD and patients without CLD. Patients were followed from the index date (date of PCI procedure) until the first occurrence of a study outcome, death, 365 days after index date, or study end date, whichever comes first. Primary outcomes were major adverse cardiovascular events (MACE) and major bleeding. MACE was a composite of myocardial infarction, stroke, revascularization, and cardiovascular-related death; major bleeding consisted of hemorrhagic stroke and gastrointestinal bleeding. Secondary outcomes were the individual components of the primary outcomes and all-cause death. Within each group, the hazard ratios (HRs) with 95% confidence intervals (CIs) of MACE and major bleeding associated with ticagrelor versus clopidogrel were calculated using a Cox proportional hazards model within a 1:1 propensity score (PS) matched cohort.
Results: The final cohort included 14,261 and 148,535 patients with and without CLD, respectively. After PS matching, the risk of MACE (with CLD, HR: 1.01, 95% CI: 0.91-1.13; without CLD, HR: 1.02, 95% CI: 0.98-1.05; P for homogeneity: 0.865) and major bleeding (with CLD, HR: 1.07, 95% CI: 0.71-1.61; without CLD, HR: 1.32, 95% CI: 1.15-1.53; P for homogeneity: 0.342) for ticagrelor versus clopidogrel do not vary with CLD status.
Conclusions: In this population-based cohort study, among patients with ACS who underwent PCI, ticagrelor versus clopidogrel was associated with a similar risk of MACE and an increased risk of major bleeding and the risks do not vary with CLD status. Our results may help improve benefit-risk assessments and guide the selection of platelet aggregation inhibitors for patients with coexisting ACS and CLD.