GLOBAL LEADERS: A Clinical Study Comparing Two Forms of Antiplatelet Therapy After Stent Implantation - GLOBAL LEADERS
Contribution To Literature:
The GLOBAL LEADERS trial failed to show that 23 months of ticagrelor after 1 month of DAPT was superior to standard therapy at preventing adverse events.
The goal of the trial was to evaluate 1 month of aspirin plus ticagrelor followed by 23 months of ticagrelor monotherapy compared with 1 year of dual antiplatelet therapy (DAPT) (aspirin plus either clopidogrel or ticagrelor) followed by 1 year of aspirin monotherapy among patients undergoing percutaneous coronary intervention (PCI) with a biolimus-eluting stent.
Patients undergoing PCI for stable or unstable coronary disease were randomized to DAPT aspirin/ticagrelor for 1 month, followed by ticagrelor for 23 months (n = 7,980) versus DAPT for 12 months (aspirin/clopidogrel for stable coronary disease or aspirin/ticagrelor for unstable coronary disease), followed by aspirin for 12 months (n = 7,988).
- Total number of enrollees: 15,968
- Duration of follow-up: 24 months
- Mean patient age: 65 years
- Percentage female: 23%
- Percentage with diabetes: 26%
- Patients undergoing PCI with a biolimus-eluting stent for stable or unstable coronary disease
- Intolerance to aspirin or ticagrelor
- Use of a cytochrome P3A4 inhibitor
- Use of fibrinolytic therapy within 24 hours of PCI
- Severe hepatic disease
- Planned coronary artery bypass grafting or noncardiac surgery
- Need for anticoagulation
- Known major bleeding
- Recent stroke
Other salient features/characteristics:
- Radial access: 74%
The primary outcome, all-cause mortality or nonfatal myocardial infarction, occurred in 3.8% of the experimental group compared with 4.4% of the control group (p = 0.073). The findings were the same in multiple tested subgroups.
- All-cause mortality: 2.8% of the experimental group vs. 3.2% of the control group (p = 0.18)
- Myocardial infarction: 1.0% of the experimental group vs. 1.3% of the control group (p = 0.14)
- Grade 3 or 5 bleeding: 2.0% of the experimental group vs. 2.1% of the control group (p = 0.77)
GLASSY (GLOBAL LEADERS Adjudication Sub-StudY) examined centrally adjudicated outcomes rather than investigator reported events. Results include:
- All-cause death, myocardial infarction, stroke, or urgent target vessel revascularization (primary efficacy endpoint for GLASSY): 7.1% of the experimental group vs. 8.4% of the control group (p for noninferiority < 0.001, p for superiority = 0.047); prespecified criterion for superiority was <0.025)
- Landmark analysis at 1 year revealed enhanced benefit favoring the experimental group for the outcome of definite stent thrombosis (p for interaction = 0.007)
- Grade 3 or 5 bleeding: 2.5% of the experimental group vs. 2.5% of the control group (p = 0.99)
Among patients who underwent PCI with a biolimus-eluting stent, 1 month of DAPT followed by ticagrelor monotherapy for 23 months was noninferior, but not superior to 12 months of DAPT followed by aspirin monotherapy for 12 months. The composite outcome, components of the primary outcome, and major bleeding were similar between treatment groups.
The current recommendations of DAPT for 6-12 months after PCI, followed by aspirin monotherapy, remain the same. The GLASSY substudy revealed that 1 month of DAPT was noninferior to 12 months of DAPT at preventing death, myocardial infarction, stroke, or urgent target vessel revascularization. One month of DAPT also failed to reduce major bleeding events compared with 12 months of DAPT.
Franzone A, McFadden E, Leonardi S, et al. Ticagrelor Alone Versus Dual Antiplatelet Therapy From 1 Month After Drug-Eluting Coronary Stenting. J Am Coll Cardiol 2019;74:2223-34.
Editorial Comment: Mehran R, Cao D, Baber U. Ticagrelor Monotherapy After Coronary Stenting: Is the GLASS Half Full or Half Empty? J Am Coll Cardiol 2019;74:2235-7.
Presented by Dr. Marco Valgimigli at the American College of Cardiology Annual Scientific Session (ACC 2019), New Orleans, LA, March 17, 2019.
Vranckx P, Valgimigli M, Jüni P, et al., on behalf of the GLOBAL LEADERS Investigators. Ticagrelor plus aspirin for 1 month, followed by ticagrelor monotherapy for 23 months vs aspirin plus clopidogrel or ticagrelor for 12 months, followed by aspirin monotherapy for 12 months after implantation of a drug-eluting stent: a multicentre, open-label, randomised superiority trial. Lancet 2018;392:940-9.
Editorial Comment: Bhatt DL. Aspirin—still the GLOBAL LEADER in antiplatelet therapy. Lancet 2018;392:896-7.
Presented by Dr. Patrick Serruys at the European Society of Cardiology Congress, Munich, Germany, August 27, 2018.
Keywords: ACC Annual Scientific Session, ACC19, ESC Congress, ESC18, Acute Coronary Syndrome, Aspirin, Adenosine, Anticoagulants, Coronary Disease, Drug-Eluting Stents, Myocardial Infarction, Myocardial Ischemia, Percutaneous Coronary Intervention, Platelet Aggregation Inhibitors, Primary Prevention
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