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

Abstract

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 participants: 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.

Conflict of interest statement

Conflict of Interest Disclosures: Dr Chichareon reported grants from Biosensors International outside the submitted work. Dr Modolo reported grants from Biosensors and FAPESP outside the submitted work. Dr Tomaniak reported lecture fees from AstraZeneca outside the submitted work. Dr Barlis reported grants as part of the GLOBAL LEADERS trial during the conduct of the study. Dr Wykrzykowska reported grants and personal feels from Abbott during the conduct of the study. Dr Piek reported nonfinancial support from Abbott Vascular and personal fees and nonfinancial support from Philips/Volcano outside the submitted work. Dr Hamm reported personal fees from AstraZeneca during the conduct of the study. Dr Steg reported other support from ECRI during the conduct of the study; grants and personal fees from Amarin, Bayer, Servier, and Sanofi; grants from AstraZeneca; and personal fees from Boehringer Ingelheim, BMS, Novartis, Pfizer, and Novo Nordisk outside the submitted work. Dr Juni reported grants from AstraZeneca, Biotronik, Biosensors International, Eli Lilly, The Medicines Company, and Canadian Institutes of Health Research outside the submitted work and serves as unpaid member of the steering group of trials funded by AstraZeneca, Biotronik, Biosensors, St Jude Medical, and The Medicines Company. Dr Windecker reported grants from Amgen, Abbott, Bayer, BMS, CSL Behring, Edwards Lifesciences, Medtronic, Polares, and Sinomed outside the submitted work. Dr Mehran reported grants from Abbott Laboratories, AstraZeneca, Bayer, Beth Israel Deaconess, BMS, CSL Behring, DSI, Medtronic, Novartis Pharmaceuticals, and OrbusNeich; personal fees from Abbott Laboratories, Boston Scientific, Medscape/WebMD, Siemens Medical Solutions, PLx Opco/PLx Pharma, Roivant Services, Sanofi, Medtelligence (Janssen Scientific Affairs), and Janssen Scientific Affairs; other support from Abbott Laboratories, Abiomed, The Medicines Company, Spectranetics/Philips/Volcano Corp, Bristol Myers Squibb, Watermark Research Partners, Claret Medical, and Elixir Medical personal fees; and nonfinancial and other support from Regeneron Pharmaceuticals outside the submitted work. Dr Serruys reported personal fees from Abbott, Biosensors, Medtronic, Micell, Sinomed, Philips/Volcano, Xeltis, and HeartFlow outside the submitted work. No other disclosures were reported.

Figures

Figure 1.. Association of Sex With Clinical Outcomes at 2 Years After Percutaneous Coronary Intervention

BARC indicates Bleeding Academic Research Consortium; HR, hazard ratio. aData were analyzed using the unadjusted Kaplan-Meier method. bAdjusted by age, diabetes, renal impairment, presentation of acute coronary syndrome, prior myocardial infarction (MI), peripheral vascular disease, chronic obstructive pulmonary disease, and history of coronary artery bypass grafting.

Figure 2.. Clinical Outcomes at 2 Years According to Sex and Antiplatelet Strategy

BARC indicates Bleeding Academic Research Consortium; HR, hazard ratio; RR, risk ratio. aData were analyzed using the unadjusted Kaplan-Meier method. bUnadjusted hazard ratio between experimental (exp) vs reference (ref) strategy in each sex.

Figure 3.. Interaction Between Sex and Antiplatelet Strategy on Primary Efficacy and Secondary Safety End Point (Bleeding Academic Research Consortium [BARC] 3 or 5 Bleeding) at 1 and 2 Years

The x-axis shows the categories of the patients according to sex and clinical presentation, and the y-axis shows the unadjusted Kaplan-Meier (KM) estimate of primary efficacy end point (all-cause mortality or new Q-wave myocardial infarction) or secondary safety end point (BARC 3 or 5 bleeding) at 1 and 2 years after percutaneous coronary intervention. ACS indicates acute coronary syndrome; CAD, coronary artery disease; DAPT, dual antiplatelet therapy.