Does CYP2C19*17 Status in Those Taking Clopidogrel Modify Post-PCI MACE Risk?

Carriers of the gain-of-function allele CYP2C19*17 who were treated with clopidogrel after percutaneous coronary intervention (PCI) had neither a reduction in major adverse cardiovascular events (MACE) nor an increase in bleeding or thrombotic events. These findings were presented during the American College of Cardiology 2021 Annual Meeting, held virtually May 15 to 17, 2021.

Researchers assessed patients (N=5147) who participated in the Tailored Antiplatelet Therapy Following PCI study (TAILOR-PCI; Clinicaltrials.gov Identifier: NCT01742117), a randomized, genotype-guided study of clopidogrel use after PCI. The primary outcome measure was MACE and the secondary outcome measure was bleeding events on the basis of CYP2C19*17 status. At baseline, over one quarter of study participants (27.8%) were carriers of CYP2C19*17.

Carriers of CYP2C19*17 have been postulated to be at decreased ischemic risk and increased bleeding risk, when treated with clopidogrel.

In this study, MACE and bleeding events occurred among 4.2% of carriers and 4.8% of non-carriers treated with clopidogrel at 12 months (hazard ratio [HR], 0.83; 95% CI, 0.60-1.15; P =.26). Thrombosis in myocardial infarction major and minor events occurred among 1.3% of the carriers and 0.9% of the non-carriers at 12 months (HR, 1.27; 95% CI, 0.68-2.39; P =.45).

Major bleeding events were higher among carriers (1.1%) than non-carriers (0.6%) on clopidogrel at 12 months, though this difference was not significant (HR, 1.95; 95% CI, 0.89-4.26; P =.098).

Risks for MACE and bleeding events were increased among patients who were aged ³80 years (HR, 3.48; 95% CI, 1.09-11.14; P =.036). No significant differences were associated with MACE and bleeding in terms of sex (women: HR, 1.70; 95% CI, 0.80-3.63; P =.17), diabetes (HR, 1.24; 95% CI, 0.58-2.66; P =.58), proton pump inhibitor use at discharge (HR, 1.43; 95% CI, 0.67-3.04; P =.35), or CYP2C19*2/*3 status (HR, 1.56; 95% CI, 0.69-3.53; P =.29).

This study may have been limited by the fact it was a subanalysis of previously collected data.

The findings indicated there were not major interaction effects between clopidogrel and CYP2C19*17 status, with no effect on risk for MACE and bleeding events after PCI.

Reference

So DYF, Baudhuin L, Farkouh M, et al. Ischemic and bleeding outcomes of carriers of CYP2C19*17 treated with clopidogrel: insights from the TAILOR-PCI study. Presented at: American College of Cardiology (ACC) 2021 Annual Meeting; May 15-17, 2021. Abstract.