Sex-Specific Differences in Clinical Outcomes After Percutaneous Coronary Intervention: Insights from the TAILOR-PCI
Mina Madan1, J Dawn Abbott2, Ryan Lennon3
1Schulich Heart CentreSunnybrook Health Sciences CentreUniversity of Toronto Toronto Ontario Canada.
Insights
In TAILOR-PCI, CYP2C19 loss-of-function alleles were common in both men and women undergoing percutaneous coronary intervention. Genotype-guided antiplatelet therapy did not significantly alter major adverse cardiac events or bleeding risks compared to standard clopidogrel treatment.
Area of Science:
- Cardiovascular Medicine
- Pharmacogenomics
- Interventional Cardiology
Background:
- The TAILOR-PCI trial investigated genotype-guided antiplatelet therapy post-percutaneous coronary intervention (PCI).
- CYP2C19 loss-of-function alleles are linked to reduced clopidogrel efficacy and increased ischemic event risk.
- A sex-specific analysis was conducted to evaluate genotype and cardiovascular outcomes.
Purpose of the Study:
- To analyze sex-specific differences in cardiovascular outcomes and bleeding events.
- To assess the impact of CYP2C19 genotype on treatment efficacy in men and women after PCI.
- To determine if genotype-guided antiplatelet therapy improves outcomes compared to conventional clopidogrel therapy, stratified by sex.
Main Methods:
- A prespecified sex-specific analysis of the TAILOR-PCI randomized trial.
- Cox proportional-hazards models were used to analyze associations between sex, CYP2C19 genotype, major adverse cardiac events (MACE), and Bleeding Academic Research Consortium (BARC) bleeding.
- Data from 5276 randomized patients were analyzed at 12 months post-PCI.
Main Results:
- Approximately 36% of both men and women carried CYP2C19 loss-of-function alleles, primarily as heterozygotes.
- Adjusted risks for MACE and BARC bleeding were comparable between women and men at 12 months.
- No significant interactions were found between sex and treatment strategy, or between sex and genotype, for MACE or bleeding outcomes.
Conclusions:
- CYP2C19 loss-of-function alleles are prevalent in both sexes undergoing PCI.
- Women and men exhibited similar risks of MACE and bleeding post-PCI.
- Genotype-guided antiplatelet therapy did not demonstrate a significant benefit over conventional therapy for reducing MACE or bleeding in either sex.
Abstract:
Background TAILOR-PCI (Tailored Antiplatelet Initiation to Lessen Outcomes due to decreased Clopidogrel Response After Percutaneous Coronary Intervention) studied genotype-guided selection of antiplatelet therapy after percutaneous coronary intervention versus conventional therapy with clopidogrel. The presence of CYP2C19 loss-of-function alleles in patients treated with clopidogrel may be associated with increased risk for ischemic events. We report a prespecified sex-specific analysis of genotyping and associated cardiovascular outcomes from this study. Methods and Results Associations between sex and major adverse cardiac events (MACE: cardiovascular death, myocardial infarction, stroke, stent thrombosis, and severe recurrent ischemia) and Bleeding Academic Research Consortium (BARC) bleeding at 12 months were analyzed using Cox proportional-hazards models. Among 5276 randomized patients, loss-of-function carriers were observed in ≈36% of both sexes, and >80% of carriers were heterozygotes. At 12 months, after adjustment for baseline differences, risks of MACE (HR , 1.28 [0.97 to 1.68]; P=0.088) and BARC bleeding (hazard ratio [HR], 1.36 [0.91 to 2.05]; P=0.14) were comparable among women and men. There were no significant interactions between sex and treatment strategy for MACE interaction P value (Pint=0.59) or BARC bleeding (Pint=0.47) nor for sex and genotype (MACE Pint=0.15, and BARC bleeding Pint=0.60). Conclusions CYP2C19 loss-of-function alleles were present in ≈1 in 3 women and men. Women had similar adjusted risks of MACE and bleeding as men following percutaneous coronary intervention. Genotype-guided therapy did not significantly reduce the risk of MACE or bleeding relative to conventional therapy for both sexes. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01742117.
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