Sex-Based Outcomes in Patients with a High Bleeding Risk after Percutaneous Coronary Intervention and 1-Month Dual Antiplatelet Therapy: A Secondary Analysis of the LEADERS FREE Randomized Clinical Trial

Importance: Female sex has been identified as a risk factor for bleeding after percutaneous coronary intervention (PCI) and may have contributed to the underuse of drug-eluting stents in women. This risk may be further enhanced among patients with a high bleeding risk. Objective: To assess the 2-year outcomes by sex in patients with a high bleeding risk who were enrolled in the LEADERS FREE trial. Design, Setting, and Participants: This cohort study is a prespecified, sex-based secondary analysis of the LEADERS FREE double-blind, randomized clinical trial that was conducted at 68 sites in 20 countries from December 2012 to May 2014. Patients with a high bleeding risk who underwent PCI and met the trial eligibility criteria were enrolled at the participating sites and followed up for up to 2 years. Interventions: Patients were randomized 1:1 to either a bare-metal stent or a polymer-free, biolimus A9-eluting drug-coated stent with 1-month of dual antiplatelet therapy. Main Outcomes and Measures: The primary safety end point was a composite of cardiac death, myocardial infarction, or stent thrombosis. The primary efficacy end point was clinically driven target lesion revascularization. Bleeding was assessed using the Bleeding Academic Research Consortium (BARC) scale, and the source of bleeding was recorded. Results: A total of 2432 patients with a high bleeding risk were included in the study. Of these patients, the mean (SD) age was 75 (9) years, and 1694 (69.7%) were men and 738 (30.3%) were women. Women and men had similar incidence of the 2-year primary safety (14.7% vs 13.6%; P =.37) and efficacy (9.2% vs 9.5%; P =.70) end points. The drug-coated stent was found to be superior to the bare-metal stent in both sexes, with lower target lesion revascularization (women: 6.3% vs 12.1%; men: 7.0% vs 12.0%; P for interaction =.70) and similar rates of the primary safety end point (women: 12.4% vs 17.0%; men: 12.6% vs 14.5%; P for interaction =.40). Overall, 2-year BARC types 3 to 5 major bleeding (10.2% vs 8.6%; P =.14) was not statistically different between the sexes, but women experienced greater BARC types 3 to 5 major bleeding within the first 30 days (5.1% vs 2.4%; P =.007) and greater vascular access site major bleeding than men (2.2% vs 0.5%; P <.001). In both sexes, vascular (women: Hazard ratio [HR], 3.45 [95% CI, 1.51-7.87]; men: HR, 4.14 [95% CI, 1.33-12.95]) and nonvascular major bleeding (women: HR, 3.76 [95% CI, 2.17-6.53]; men: HR, 4.62 [95% CI, 3.23-6.61]) were associated with greater 2-year mortality. Conclusions and Relevance: This study found no sex differences in the ischemic outcomes of patients with a high bleeding risk after PCI, but women appeared to demonstrate greater early bleeding and major bleeding from the vascular access site. Both women and men with major bleeding seemed to experience worse 2-year mortality, suggesting that bleeding avoidance strategies should be uniformly adopted for all patients, with close attention dedicated to women to avoid denying them the benefits of PCI. Trial Registration: ClinicalTrials.gov Identifier: NCT02843633.