Efficacy and safety of clopidogrel and ticagrelor in acute coronary syndrome patients with CYP2C19 loss-of-function alleles after percutaneous coronary intervention: based on the Global Registry of Acute Coronary Events score

Abstract

Background

The selection of P2Y12 inhibitors for acute coronary syndrome patients after percutaneous coronary intervention (PCI) remains controversial among East Asian patients.

Objectives

This study aimed to identify the optimal P2Y12 inhibitor selection for the East Asian population carrying CYP2C19 loss-of-function (LOF) alleles based on the Global Registry of Acute Coronary Events (GRACE) score.

Methods

Between March 2016 and March 2019, a cohort of 8683 patients diagnosed with acute coronary syndrome who survived PCI were enrolled in this study. All patients carried the LOF allele and could calculate GRACE scores. The primary outcome was ischemic events (cardiac death, nonfatal myocardial infarction, and ischemic stroke) within 12 months. Secondary outcomes included the components of the primary outcome, all-cause mortality, Bleeding Academic Research Consortium (BARC) types 2, 3, and 5 bleeding events, and BARC types 3 and 5 bleeding events. The propensity score matching method was used to balance the baseline characteristics of patients. The Kaplan–Meier/log-rank test was adopted for the result analysis, and Cox regression was employed for adjusting for confounding factors.

Results

The low-risk group comprised 5496 patients (63.3%), while the intermediate- to high-risk group included 3187 patients (36.7%) in the study population stratified by GRACE scores. The follow-up results revealed that in patients at low risk, clopidogrel and ticagrelor had comparable effects in preventing ischemic events. However, ticagrelor use was associated with a higher risk of BARC types 2, 3, and 5 bleeding events (hazard ratio [HR], 2.08; 95% CI, 1.43-3.02; P < .001) and BARC types 3 and 5 bleeding events (HR, 2.69; 95% CI, 1.57-4.63; P < .001) compared with clopidogrel use. In patients at intermediate to high risk, ticagrelor treatment was associated with a lower risk of stroke (HR, 0.18; 95% CI, 0.04-0.82; P = .026), while the risk of ischemic events or bleeding was comparable between the 2 treatment groups.

Conclusion

These real-world data on East Asian patients with CYP2C19 LOF alleles suggest that GRACE risk stratification may help differentiate ischemic and bleeding risks post-PCI.