Ticagrelor versus Clopidogrel in Acute Coronary Syndrome: A Prospective Cohort Study in CYP2C19-Genotyped Patients

OBJECTIVES

CYP2C19 genotype-guided antiplatelet therapy reduces major adverse cardiovascular events without significantly increasing bleeding compared to standard therapy. However, genetic testing is not yet routinely recommended; P2Y12 inhibitor selection is guided by other factors. We sought to conduct a pragmatic study to provide CYP2C19 genetic information to clinicians, and study how the use of P2Y12 inhibitor with respect to CYP2C19 phenotype modified bleeding and ischemic outcomes.

MATERIALS AND METHODS

This was a prospective cohort study on 950 patients with acute coronary syndrome post-percutaneous coronary intervention. Recruitment took place from October 2020 to February 2024. All patients were prescribed dual antiplatelet therapy (aspirin and clinician-selected P2Y12 inhibitor) and underwent CYP2C19 genetic testing. Bleeding events and major adverse cardiac and cerebrovascular events (MACCE) until 12 months after the index hospitalization for ACS were recorded. Patients were stratified based on CYP2C19 genotype and P2Y12 inhibitor for statistical analysis.

RESULTS

Bleeding events occurred more frequently in patients receiving ticagrelor (Non-LoF-Ticagrelor: 38/235, 16.2%; LoF-Ticagrelor: 61/483, 12.6%) than clopidogrel (Non-LoF-Clopidogrel: 9/141, 6.4%; LoF-Clopidogrel: 6/91, 6.6%). The difference in bleeding event rates (p=0.013) was driven by greater bleeding in Non-LoF-Ticagrelor than Non-LoF-Clopidogrel (p=0.006). After controlling for covariates, patients receiving ticagrelor had higher bleeding risk compared to Non-LoF-Clopidogrel (hazard ratio (95% confidence interval) for Non-LoF-Ticagrelor: 3.086 (1.457-6.537), p=0.003; LoF-Ticagrelor: 2.499 (1.214-5.142), p=0.013). MACCE occurred in 32/950 patients (3.4%), and there was no significant difference in MACCE between groups.

CONCLUSION

CYP2C19 genetic testing identifies Non-LoF carriers who may benefit from de-escalating ticagrelor to clopidogrel, reducing bleeding events.