title: Impact of Bleeding and Bivalirudin Therapy on Mortality Risk in Women Undergoing Percutaneous Coronary Intervention (from the REPLACE-2, ACUITY, and HORIZONS-AMI Trials).
abstract: Women have higher bleeding complication and mortality rates after percutaneous coronary interventions (PCI). The contribution of female gender to bleeding and mortality is poorly understood. We evaluated the effect of gender and bleeding on outcomes of patients treated with bivalirudin during PCI by performing a patient-level pooled analysis of 3 randomized controlled trials (the Randomized Evaluation in PCI Linking Angiomax to Reduced Clinical Events, Acute Catheterization and Urgent Intervention Triage strategY, and Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction) comparing bivalirudin versus heparin plus glycoprotein IIb/IIIa inhibitor (GPI) treatment in patients undergoing PCI. Of 14,784 patients, 7,413 patients received bivalirudin (1,870 women) and 7,371 patients received heparin + GPI (1,910 women). Women had significantly higher 30-day non-coronary artery bypass grafting (CABG)-related major bleeding rates (7.6% vs 3.8%, p <0.0001). After multivariate adjustment, female gender increased the hazard of major bleeding by 80% (hazard ratio 1.80, 95% confidence interval 1.52 to 2.11, p <0.001). Furthermore, women had a higher 1-year mortality rate (3.7% vs 2.7%, p = 0.002) than men; 30-day major bleeding was the strongest independent predictor of 1-year mortality in women (hazard ratio 2.48, 95% confidence interval 1.57 to 3.91, p = 0.001). Bivalirudin therapy in women reduced 30-day non-CABG-related major bleeding (5.6% vs 9.7%, p <0.0001) and 1-year mortality (2.9% vs 4.4%, p = 0.02) compared to standard therapy. In conclusion, in this cohort of patients treated for acute coronary syndrome and ST-segment elevation myocardial infarction, women have a near 2-fold increase in bleeding complications compared to men after PCI. Bleeding complications rather than gender is the strongest independent predictor of 1-year mortality in patients undergoing PCI. Furthermore, we observed a more pronounced clinical benefit in women treated with bivalirudin including a 44% reduction in major bleeding and a significant reduction in mortality rates at 1 year.
authors.affiliation: Division of Cardiovascular Medicine, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut.
authors.forename: Vivian G
authors.initials: VG
authors.lastname: Ng
authors.affiliation: Bristol Heart Institute, University Hospitals Bristol, Bristol, United Kingdom.
authors.forename: Andreas
authors.initials: A
authors.lastname: Baumbach
authors.affiliation: Department of Interventional Cardiology, Hosp Italiano, Buenos Aires, Argentina.
authors.forename: Liliana
authors.initials: L
authors.lastname: Grinfeld
authors.affiliation: Department of Cardiovascular Medicine, Cleveland Clinic Foundation, Cleveland, Ohio.
authors.forename: A Michael
authors.initials: AM
authors.lastname: Lincoff
authors.affiliation: Columbia University Medical Center and the Cardiovascular Research Foundation, New York, New York.
authors.forename: Roxana
authors.initials: R
authors.lastname: Mehran
authors.affiliation: Columbia University Medical Center and the Cardiovascular Research Foundation, New York, New York.
authors.forename: Gregg W
authors.initials: GW
authors.lastname: Stone
authors.affiliation: Division of Cardiovascular Medicine, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut. Electronic address: Alexandra.lansky@yale.edu.
authors.forename: Alexandra J
authors.initials: AJ
authors.lastname: Lansky
mesh_terms: D000368:Aged; D000991:Antithrombins / Q000008:administration & dosage / Q000009:adverse effects; D001118:Argentina / Q000453:epidemiology; D004562:Electrocardiography; D005260:Female; D005500:Follow-Up Studies; D006470:Hemorrhage / Q000139:chemically induced* / Q000401:mortality; D006629:Hirudins / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000401:mortality / Q000628:therapy*; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000009:adverse effects; D062645:Percutaneous Coronary Intervention / Q000379:methods*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects; D012307:Risk Factors; D015996:Survival Rate / Q000639:trends; D013997:Time Factors; D006113:United Kingdom / Q000453:epidemiology; D014481:United States / Q000453:epidemiology
chemical_list: D000991:Antithrombins; D006629:Hirudins; D010446:Peptide Fragments; D011994:Recombinant Proteins; C074619:bivalirudin