Comparative Effectiveness of Clopidogrel vs. Potent P2Y₁₂ Inhibitors in CYP2C19 Normal Metabolizers Following...

Evidence suggests that cytochrome P450 2C19 (CYP2C19) genotyping may guide clopidogrel therapy after percutaneous coronary intervention (PCI). However, evidence on the effectiveness of clopidogrel and potent P2Y12 inhibitors (ticagrelor or prasugrel) in patients with CYP2C19 normal metabolizer (NM) genotype remain limited.

This retrospective cohort study utilized nationwide genetic data from China Medical University Hospital, Taiwan. We included patients undergoing PCI with CYP2C19 NM who received dual antiplatelet therapy (DAPT) between 2004 and 2020. The primary outcome was a composite of thrombotic events, including MI, stroke or rehospitalization for stent implantation. Major bleeding events included intracranial and gastrointestinal bleeding requiring hospitalization. Inverse probability of treatment weighting balanced baseline covariates. Hazard ratios and 95% confidence intervals were estimated using Cox regression.

Among patients with CYP2C19 NM with MI (n = 1825), potent P2Y₁₂ inhibitors were associated with a reduced risk of thrombotic events in patients with MI (HR: 0.76; 95% CI: 0.58-0.98). However, no difference in bleeding risk was observed between treatment groups. Several sensitivity analyses, including as-treated analysis, supported the robustness of our findings.

Among patients with MI with CYP2C19 NM undergoing percutaneous coronary intervention, the use of potent P2Y₁₂ inhibitors was associated with a reduced risk of thrombotic events at 1 year compared to clopidogrel. These findings indicate genotype-guided de-escalation strategies warrant further investigation across diverse clinical settings.