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Published on: November 8, 2024
Antiplatelet Therapy and Bleeding Outcomes With CYP2C19 Genotyping
James C Coons1,2, James M Stevenson3, Ami Patel2
1Heart and Vascular Institute and Department of Pharmacy, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
Insights
Antiplatelet therapy with potent agents like ticagrelor or prasugrel increases bleeding risk in patients after percutaneous coronary intervention (PCI). CYP2C19 genotyping may guide de-escalation to clopidogrel, especially after bleeding events.
Area of Science:
- Cardiology
- Pharmacogenomics
- Clinical Research
Background:
- Antiplatelet therapy is crucial after percutaneous coronary intervention (PCI).
- The role of CYP2C19 genotyping in guiding antiplatelet therapy and its impact on bleeding risk in real-world settings remains under-investigated.
- P2Y12 inhibitors are commonly used post-PCI.
Purpose of the Study:
- To evaluate the impact of antiplatelet therapy, guided by CYP2C19 genotyping, on bleeding events in a real-world post-PCI population.
- To assess the association between different P2Y12 inhibitors and bleeding risk.
- To investigate the rates and predictors of antiplatelet de-escalation.
Main Methods:
- Prospective, single-center cohort study with 1-year follow-up.
- Included patients undergoing PCI, CYP2C19 genotyping, and P2Y12 inhibitor therapy.
- Primary outcome: time to first bleed (Bleeding Academic Research Consortium criteria). Secondary outcomes: major bleeding, antiplatelet switching.
Main Results:
- A high incidence of bleeding (33%) was observed post-PCI.
- Treatment with ticagrelor or prasugrel was associated with a significantly increased risk of any bleeding (aHR 2.04) and major bleeding compared to clopidogrel.
- This increased bleeding risk with potent agents was also observed in non-carriers of CYP2C19 no-function alleles.
- Antiplatelet de-escalation to clopidogrel occurred in 36% of patients on potent agents, more frequently after a bleed in non-carriers of no-function alleles.
Conclusions:
- Bleeding is a frequent complication in patients on antiplatelet therapy post-PCI.
- Potent P2Y12 inhibitors (ticagrelor, prasugrel) are linked to higher bleeding risks, particularly in individuals without CYP2C19 no-function alleles.
- Genotype-guided de-escalation of antiplatelet therapy warrants further investigation in prospective clinical trials.
Purpose:
The impact of antiplatelet therapy with availability of CYP2C19 genotyping on bleeding in a real-world setting has not been extensively studied.
Methods:
Prospective, single-center, cohort study conducted between December 2015 and October 2019 with 1-year follow-up. Patients underwent percutaneous coronary intervention (PCI), CYP2C19 genotyping, and received P2Y12 inhibitor therapy. The primary outcome was time to first bleed of any severity using Bleeding Academic Research Consortium criteria. Secondary outcomes included time to first major bleed and rates of antiplatelet switching.
Results:
The primary outcome occurred in 697 of 2091 (33%) participants at a median of 15 days. Major bleeding occurred in 176 (8%) of patients. Compared to clopidogrel, treatment with ticagrelor or prasugrel was associated with increased risk of any bleeding (adjusted HR [aHR] 2.04, 95% CI 1.69-2.46). For patients without CYP2C19 no function alleles, treatment with prasugrel or ticagrelor was associated with increased risk of any bleeding (aHR 2.31, 95% CI 1.83-2.90). Similar associations were observed for major bleeding. No difference in ischemic events was observed. Among patients discharged on ticagrelor or prasugrel, 199 (36%) were de-escalated to clopidogrel within 1 year. De-escalation was more likely after a bleed if patients did not have a no function allele (35.9% vs 19.1%; P = .02).
Conclusion:
Bleeding is common in post-PCI patients on antiplatelet therapy. Patients on high potency agents had higher bleeding risk in the population at-large and in non-carriers of CYP2C19 no function alleles. Genotype-guided antiplatelet de-escalation should be further explored in prospective studies.
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