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Original Investigation
November 6, 2019

Association of Sex With Outcomes in Patients Undergoing Percutaneous Coronary Intervention: A Subgroup Analysis of the GLOBAL LEADERS Randomized Clinical Trial

Author Affiliations
  • 1Heart Center, Department of Clinical and Experimental Cardiology, Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands
  • 2Cardiology Unit, Department of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Songkhla, Thailand
  • 3Cardiology Division, Department of Internal Medicine, University of Campinas, Campinas, Brazil
  • 4Erasmus Medical Center, Erasmus University, Rotterdam, the Netherlands
  • 5First Department of Cardiology, Medical University of Warsaw, Warsaw, Poland
  • 6Department of Cardiology, Fondazione Cardiocentro Ticino, Lugano, Switzerland
  • 7Royal Bournemouth and Christchurch National Health Services Trust, Bournemouth, England
  • 8Division of Interventional Cardiology, Cardio-Thoracic-Vascular Department, San Raffaele Scientific Institute, Milan, Italy
  • 9GCS ES Axium Rambot, Aix en Provence, France
  • 10St Vincent’s and Northern Hospitals, Melbourne Medical School, The University of Melbourne, Victoria, Australia
  • 11East Lancashire Hospitals National Health Services Trust, Blackburn, Lancashire, England
  • 12Kerckhoff Heart Center, Campus University of Giessen, Bad Nauheim, Germany
  • 13French Alliance for Cardiovascular Trials; Hôpital Bichat, AP-HP; Université Paris-Diderot; INSERM U-1148; Paris, France
  • 14Royal Brompton Hospital, Imperial College, London, England
  • 15Applied Health Research Centre, Li Ka Shing Knowledge Institute, St Michael’s Hospital, Department of Medicine, University of Toronto, Toronto, Canada
  • 16Department of Cardiology, Bern University Hospital, Bern, Switzerland
  • 17Cardialysis Clinical Trials Management and Core Laboratories, Westblaak 98, Rotterdam, the Netherlands
  • 18Interventional Cardiovascular Research and Clinical Trials, The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, New York
  • 19National Heart and Lung Institute, Imperial College London, London, England
JAMA Cardiol. Published online November 6, 2019. doi:https://doi.org/10.1001/jamacardio.2019.4296
Key Points

Question  What is the association of sex with patient outcomes after percutaneous coronary intervention?

Findings  In this prespecified subgroup analysis of the GLOBAL LEADERS randomized clinical trial, there was no between-sex difference in the risk of 2-year all-cause mortality or new Q-wave myocardial infarction. The risks of bleeding and hemorrhagic stroke in women were higher than in men, and compared with dual antiplatelet therapy, ticagrelor monotherapy was associated with lower risk of bleeding at 1 year in men but not in women.

Meaning  The effect of antiplatelet strategy on bleeding at 1 year may be different between the sexes.


Importance  Women experience worse ischemic and bleeding outcomes after percutaneous coronary intervention (PCI).

Objectives  To assess the association of sex with patient outcomes at 2 years after contemporary PCI and with the efficacy and safety of 2 antiplatelet strategies.

Design, Setting, and Analysis  This study is a prespecified subgroup analysis of the investigator-initiated, prospective, randomized GLOBAL LEADERS study evaluating 2 strategies of antiplatelet therapy after PCI in an unselected population including 130 secondary/tertiary care hospitals in different countries. The main study enrolled 15 991 unselected patients undergoing PCI between July 2013 and November 2015. Patients had an outpatient clinic visit at 30 days and 3, 6, 12, 18, and 24 months after the index procedure. Data were analyzed between January 1, 2019, and March 31, 2019.

Interventions  Eligible patients were randomized to either the experimental or reference antiplatelet strategy. Experimental strategy consisted of 1 month of dual antiplatelet therapy (DAPT) followed by 23 months of ticagrelor monotherapy, while the reference strategy comprised of 12 months of DAPT followed by 12 months of aspirin monotherapy.

Main Outcomes and Measures  The primary efficacy end point was the composite of all-cause mortality and new Q-wave myocardial infarction at 2 years. The secondary safety end point was Bleeding Academic Research Consortium type 3 or 5 bleeding.

Results  Of the 15 968 patients included in this study, 3714 (23.3%) were women. The risk of the primary end point at 2 years was similar between women and men (adjusted hazard ratio [HR], 1.00; 95% CI, 0.83-1.20). Compared with men, women had higher risk of Bleeding Academic Research Consortium type 3 or 5 bleeding (adjusted HR, 1.32; 95% CI, 1.04-1.67) and hemorrhagic stroke at 2 years (adjusted HR, 4.76; 95% CI, 1.92-11.81). At 2 years, there was no between-sex difference in the efficacy and safety of the 2 antiplatelet strategies. At 1 year, compared with DAPT, ticagrelor monotherapy was associated with a lower risk of bleeding in men (HR, 0.72; 95% CI, 0.53-0.98) but not in women (HR, 1.23; 95% CI, 0.80-1.89; P for interaction = .045).

Conclusions and Relevance  Compared with men, women experienced a higher risk of bleeding and hemorrhagic stroke after PCI. The effect of 2 antiplatelet strategies on death and Q-wave myocardial infarction following PCI did not differ between the sexes at 2 years.

Trial Registration  ClinicalTrials.gov identifier: NCT01813435