Abstract
Background: We hypothesised that ticagrelor, in combination with aspirin for 1 month, followed by ticagrelor alone, improves outcomes after percutaneous coronary intervention compared with standard antiplatelet regimens. Methods: GLOBAL LEADERS was a randomised, open-label superiority trial at 130 sites in 18 countries. Patients undergoing percutaneous coronary intervention with a biolimus A9-eluting stent for stable coronary artery disease or acute coronary syndromes were randomly assigned (1:1) to 75–100 mg aspirin daily plus 90 mg ticagrelor twice daily for 1 month, followed by 23 months of ticagrelor monotherapy, or standard dual antiplatelet therapy with 75–100 mg aspirin daily plus either 75 mg clopidogrel daily (for patients with stable coronary artery disease) or 90 mg ticagrelor twice daily (for patients with acute coronary syndromes) for 12 months, followed by aspirin monotherapy for 12 months. Randomisation was concealed, stratified by centre and clinical presentation (stable coronary artery disease vs acute coronary syndrome), and blocked, with randomly varied block sizes of two and four. The primary endpoint at 2 years was a composite of all-cause mortality or non-fatal centrally adjudicated new Q-wave myocardial infarction as assessed by a core lab in a blinded manner. The key secondary safety endpoint was site-reported bleeding assessed according to the Bleeding Academic Research Consortium criteria (grade 3 or 5). Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01813435, and is closed to new participants, with follow-up completed. Findings: Between July 1, 2013, and Nov 9, 2015, 15 968 participants were randomly assigned, 7980 to the experimental group and 7988 to the control group. At 2 years, 304 (3·81%) participants in the experimental group had died or had a non-fatal centrally adjudicated new Q-wave myocardial infarction, compared with 349 (4·37%) participants in the control group (rate ratio 0·87 [95% CI 0·75–1·01]; p=0·073]). There was no evidence for a difference in treatment effects for the primary endpoint across prespecified subgroups of acute coronary syndromes and stable coronary artery disease (p=0·93). Grade 3 or 5 bleeding occurred in 163 participants in the experimental group and 169 in the control group (2·04% vs 2·12%; rate ratio 0·97 [95% CI 0·78–1·20]; p=0·77). Interpretation: Ticagrelor in combination with aspirin for 1 month followed by ticagrelor alone for 23 months was not superior to 12 months of standard dual antiplatelet therapy followed by 12 months of aspirin alone in the prevention of all-cause mortality or new Q-wave myocardial infarction 2 years after percutaneous coronary intervention. Funding: AstraZeneca, Biosensors, and The Medicines Company.
| Original language | English |
|---|---|
| Journal | The Lancet |
| Volume | 392 |
| Issue number | 10151 |
| Pages (from-to) | 940-949 |
| Number of pages | 10 |
| ISSN | 0140-6736 |
| DOIs | |
| Publication status | Published - 15.09.2018 |
Funding
GLOBAL LEADERS was sponsored by the European Clinical Research Institute, which received funding from Biosensors International, AstraZeneca, and the Medicines Company. PJ is a Tier 1 Canada Research Chair in Clinical Epidemiology of Chronic Diseases. This research was completed, in part, with funding from the Canada Research Chairs Programme. PV has received personal fees from AstraZeneca and the Medicines Company during the conduct of the study and personal fees from Bayer Health Care, Terumo, and Daiichi-Sankyo outside the submitted work. MV has received personal fees from Abbott, AstraZeneca, Chiesi, Bayer, Daiichi Sankyo, Terumo, Alvi Medical, and Amgen, and grants from the Swiss National Foundation, Terumo, Medicure, Abbott, and AstraZeneca, outside the submitted work. PJ's institution has received research grants from AstraZeneca, Biotronik, Biosensors International, Eli Lilly, and the Medicines Company, outside the submitted work. PJ has served as an unpaid member of the steering group of trials funded by AstraZeneca, Biotronik, Biosensors, St Jude Medical, and the Medicines Company. CH has received personal fees from AstraZeneca outside the submitted work. PGS has received research grants from Bayer/Janssen, grants and personal fees from Merck, Sanofi, and Amarin, personal fees from Amgen, Bristol-Myers Squibb, Boehringer Ingelheim, Pfizer, Novartis, Regeneron, Lilly, and AstraZeneca, and grants, personal fees, and non-financial support from Servier, all outside the submitted work. DH is affiliated with Clinical Trials Unit Bern at the University of Bern, which has a staff policy of not accepting honoraria or consultancy fees. However, it is involved in the design, conduct, or analysis of clinical studies funded by not-for-profit and for-profit organisations, including pharmaceutical and medical device companies. An up-to-date list of Clinical Trials Unit Bern's conflicts of interest is available online . EPM has received personal fees from the European Clinical Research Institute during the conduct of the study, grants from AstraZeneca, personal fees from Abbott Vascular and Daiichi Sankyo, non-financial support from Menarini Ireland, and grants from Bayer and Terumo outside the submitted work. YO has received consultancy fees from Abbott Vascular. HM has received personal fees from AstraZeneca, Bayer, Bristol-Myers Squibb, Boehringer Ingelheim, Daiichi Sankyo, and Pfizer. RJVG has received grants and personal fees from Abbott Vascular, grants from Boston Scientific outside the submitted work. KH has received personal fees from AstraZeneca, Sanofi Aventis, and Biosensors outside the submitted work. PWS has received personal fees from Abbot Laboratories, AstraZeneca, Biotronik, Cardialysis, GLG Research, Medtronic, Sino Medical Sciences Technology, Société Europa Digital Publishing, Stentys France, Svelte Medical Systems, Philips/Volcano, St Jude Medical, Qualimed, and Xeltis, outside the submitted work. SW's institution has research contracts with Abbott, Amgen, Bayer, Biotronik, Boston Scientific, Edwards Lifesciences, Medtronic, St Jude Medical, Symetis SA, and Terumo outside the submitted work. All other authors declare no competing interests.
Research Areas and Centers
- Centers: Cardiological Center Luebeck (UHZL)
DFG Research Classification Scheme
- 2.22-12 Cardiology, Angiology
