Sex-Specific Differences in Clinical Outcomes After Percutaneous Coronary Intervention: Insights from the TAILOR-PCI Trial

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 (P_int=0.59) or BARC bleeding (P_int=0.47) nor for sex and genotype (MACE P_int=0.15, and BARC bleeding P_int=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.

Keywords: TAILOR‐PCI; genotype; sex differences.

Figure 1. Study cohort.

A total of 5302 patients were randomized; however, only 5276 patients were eligible for analysis. ACS indicates acute coronary syndrome; CAD, stable coronary artery disease; and PCI, percutaneous coronary intervention.

Figure 2. Genotype status.

Genotype status among 5276 randomized patients: female patients n=1293, and male patients n=3983.

Figure 3. Event rates among all randomized patients according to sex.

Kaplan–Meier estimated event rates (unadjusted) in female and male subjects for the primary end point of time to cardiovascular mortality, myocardial infarction, stroke, stent thrombosis, or severe recurrent ischemia (A) and the safety end point time to Bleeding Academic Research Consortium 2, 3, 5 bleeding (B); n=5276 randomized patients: female patients n=1293, male patients n=3983. HR indicates hazard ratio.

Figure 4. Analysis of interaction between sex and treatment strategy.

Interaction analysis between sex and randomized treatment strategy. A, All randomized patients (n=5, 276). (B) LOF cohort (n=1849 patients). BARC indicates Bleeding Academic Research Consortium; CT, conventional therapy; CV, cardiovascular; GG, genotype‐guided therapy; and LOF, loss of function. Adjusted hazard ratios and 95% CIs are shown.

Figure 5. Analysis of interaction between sex and genotype.

n=5044 patients. BARC indicates Bleeding Academic Research Consortium; CV, cardiovascular; and LOF, loss of carrier. Adjusted hazard ratios and 95% CIs are shown.