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Published on: November 8, 2024
Outcomes of Ticagrelor Versus High-dose Clopidogrel in CYP2C19 Intermediate Metabolizer Undergoing Percutaneous
Hui-Min Huang1,2, Feng-Ying Ran1,2, Jun Chen1
1Sinopharm Dongfeng General Hospital, Hubei University of Medicine, Shiyan, China.
Insights
For patients with CYP2C19 intermediate metabolizer status after coronary intervention, ticagrelor did not significantly reduce major adverse cardiac events compared to clopidogrel, but increased bleeding risk.
Area of Science:
- Cardiology
- Pharmacogenomics
Background:
- Antiplatelet therapy selection for CYP2C19 intermediate metabolizers (IM) remains controversial.
- Percutaneous coronary intervention for acute coronary syndromes necessitates optimized antiplatelet strategies.
Purpose of the Study:
- To compare the clinical efficacy and safety of ticagrelor versus high-dose clopidogrel in CYP2C19 IM patients post-percutaneous coronary intervention.
- To evaluate the impact of these antiplatelet agents on major adverse cardiac and cerebrovascular events (MACCE) and bleeding.
Main Methods:
- Retrospective, single-center study of 532 CYP2C19 IM patients.
- Patients received either ticagrelor or high-dose clopidogrel.
- Outcomes assessed included MACCE (cardiovascular death, myocardial infarction, stroke, stent thrombosis) and Bleeding Academic Research Consortium (BARC) bleeding events at 12 months.
- Inverse probability treatment weighting (IPTW) was used for confounder adjustment.
Main Results:
- No significant difference in MACCE rates between ticagrelor and clopidogrel groups (IPTW-adjusted HR: 0.71; 95% CI: 0.32-1.58).
- Ticagrelor was associated with a statistically significant higher incidence of BARC type 2, 3, or 5 bleeding events compared to clopidogrel (IPTW-adjusted HR: 2.29; 95% CI: 1.10-4.78).
Conclusions:
- Ticagrelor treatment in CYP2C19 IM patients post-percutaneous coronary intervention did not show a significant benefit in reducing MACCE compared to high-dose clopidogrel.
- Ticagrelor significantly increased the risk of bleeding events in this patient population.
- Further research is warranted to clarify the association between these antiplatelet therapies and MACCE in CYP2C19 IM.
Abstract:
Guidelines on antiplatelet recommendation for CYP2C19 intermediate metabolizer (IM) have not come to an agreement. This study aimed to evaluate the clinical benefit of ticagrelor when compared with high-dose clopidogrel in CYP2C19 IM after percutaneous coronary intervention for acute coronary syndromes. Patients were enrolled according to CYP2C19 genotype and individual antiplatelet therapy. Patient characteristics and clinical outcomes were collected through electronic medical record system. The primary outcome was major adverse cardiac and cerebrovascular event (MACCE), namely a composite of death from cardiovascular causes, myocardial infarction, stroke, and stent thrombosis within 12 months. The secondary outcome was Bleeding Academic Research Consortium scale bleeding events within 12 months. The Cox proportional hazards regression model was performed, with inverse probability treatment weighting (IPTW) adjusting for potential confounders. A total of 532 CYP2C19 IM were enrolled in this retrospective single-center study. No statistically significant difference in incidence rate of MACCE was found between patients receiving ticagrelor versus clopidogrel (7.01 vs. 9.52 per 100 patient-years; IPTW-adjusted hazard ratio 0.71; 95% confidence interval: 0.32-1.58; adjusted log-rank P = 0.396), but the incidence rate of Bleeding Academic Research Consortium type 2, 3, or 5 bleeding events was statistically higher in the loss of function-ticagrelor group than in the loss of function-clopidogrel group (13.53 vs. 6.16 per 100 patient-years; IPTW-adjusted hazard ratio: 2.29; 95% confidence interval: 1.10-4.78; adjusted log-rank P = 0.027). Ticagrelor treatment in CYP2C19 IM resulted in a statistically higher risk of bleeding compared with high-dose clopidogrel, whereas a clear association between treatments and MACCE warrants further investigations.
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