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Clopidogrel Use in CYP2C19 Loss-of-Function Carriers With High Bleeding Risk After Percutaneous Coronary Intervention
Yuichi Sawayama1, Yukinori Tomita2, Soji Kohyama1
1Department of Cardiovascular Medicine, Shiga University of Medical Science.
Insights
For patients with high bleeding risk undergoing percutaneous coronary intervention, clopidogrel use in CYP2C19 loss-of-function carriers is linked to more ischemic events. This highlights risks associated with specific genetic profiles and antiplatelet therapy choices.
Area of Science:
- Cardiology
- Pharmacogenomics
- Interventional Cardiology
Background:
- The impact of clopidogrel in patients with high bleeding risk (HBR) and CYP2C19 loss-of-function (LOF) following percutaneous coronary intervention (PCI) remains unclear.
- CYP2C19 genetic variations affect clopidogrel metabolism and efficacy, posing potential risks in specific patient populations.
- High bleeding risk criteria, such as the Academic Research Consortium definition, identify patients susceptible to bleeding complications.
Purpose of the Study:
- To investigate the association between clopidogrel use in CYP2C19 LOF carriers with HBR and adverse clinical outcomes after PCI.
- To compare ischemic and bleeding events between patients with decreased P2Y12 inhibitor action versus retained action.
Main Methods:
- Retrospective observational study of 618 patients undergoing PCI with available CYP2C19 polymorphism data.
- Patients with HBR were stratified into groups based on P2Y12 inhibitor action: decreased (clopidogrel in CYP2C19 LOF carriers) and retained.
- Clinical outcomes at 1 year were compared using inverse probability-weighted Cox proportional hazard regression.
Main Results:
- The primary ischemic outcome (cardiovascular death, myocardial infarction, ischemic stroke) was significantly higher in the decreased action group (10.2%) compared to the retained group (3.0%).
- No significant difference was observed in the primary bleeding outcome (BARC 3 or 5) between the decreased (3.4%) and retained (6.9%) groups.
- No significant interactions were found between treatment groups and HBR status for either ischemic or bleeding outcomes.
Conclusions:
- In patients with high bleeding risk, clopidogrel use in CYP2C19 loss-of-function carriers is significantly associated with an increased risk of ischemic events post-PCI.
- These findings underscore the importance of considering pharmacogenetic profiles in antiplatelet therapy selection for HBR patients undergoing PCI.
Background:
It is not known whether clopidogrel use in cytochrome P450 (CYP) 2C19 loss-of-function (LOF) carriers with high bleeding risk (HBR) contributes to adverse outcomes after percutaneous coronary intervention (PCI).
Methods And Results:
This retrospective observational study included 618 consecutive patients with available CYP2C19 polymorphism information who underwent PCI between September 2014 and August 2021. Patients with HBR (319 [52%] met the Academic Research Consortium definition) were divided into 2 groups according to P2Y12inhibitor action, namely decreased (i.e., clopidogrel in CYP2C19 LOF carriers) and retained (i.e., clopidogrel in CYP2C19 LOF non-carriers or prasugrel regardless of CYP2C19 polymorphisms), and clinical outcomes at 1 year were compared using inverse probability-weighted Cox proportional hazard regression. The primary ischemic outcome (a composite of cardiovascular death, myocardial infarction, or ischemic stroke) was significantly higher in the decreased than retained group (10.2% vs. 3.0%; adjusted hazard ratio [aHR] 2.78; 95% confidence interval [CI] 1.40-5.52; P=0.004). The primary bleeding outcome (Bleeding Academic Research Consortium 3 or 5) did not differ significantly between the decreased and retained groups (3.4% vs. 6.9%, respectively; aHR 0.48; 95% CI 0.22-1.01; P=0.054). There were no interactions between the treatment groups and HBR status in primary ischemic and bleeding outcomes.
Conclusions:
Among patients with HBR, clopidogrel use in CYP2C19 LOF carriers was significantly associated with increased ischemic events after PCI.
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