Pascal Vranckx1, Marco Valgimigli2, Peter Jüni3, Christian Hamm4, Philippe Gabriel Steg5, Dik Heg6, Gerrit Anne van Es7, Eugene P McFadden8, Yoshinobu Onuma9, Cokky van Meijeren10, Ply Chichareon11, Edouard Benit1, Helge Möllmann4, Luc Janssens12, Maurizio Ferrario13, Aris Moschovitis2, Aleksander Zurakowski14, Marcello Dominici15, Robert Jan Van Geuns16, Kurt Huber17, Ton Slagboom18, Patrick W Serruys19, Stephan Windecker20. 1. Jessa Ziekenhuis, Faculty of Medicine and Life Sciences at the Hasselt University, Hasselt, Belgium. 2. Department of Cardiology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland. 3. Applied Health Research Centre, Li Ka Shing Knowledge Institute of St Michael's Hospital, Department of Medicine and Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, ON, Canada. 4. Kerckhoff Heart and Thorax Center, Bad Nauheim, Germany. 5. Université Paris-Diderot, Hôpital Bichat, Assistance Publique-Hôpitaux de Paris, INSERM U-1148, French Alliance for Cardiovascular Trials, Paris, France; National Heart and Lung Institute, Royal Brompton Hospital, Imperial College London, London, UK. 6. Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland. 7. European Cardiovascular Research Institute, Rotterdam, Netherlands. 8. Cork University Hospital, Cork, Ireland. 9. Erasmus Medical Center, Rotterdam, Netherlands; Cardialysis, Rotterdam, Netherlands. 10. Cardialysis, Rotterdam, Netherlands. 11. Academic Medical Center of Amsterdam, Amsterdam, Netherlands. 12. Imeldaziekenhuis, Bonheiden, Belgium. 13. UOC Cardiologia, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy. 14. American Heart of Poland, Center for Cardiovascular Research and Development, Katowice, Poland. 15. Azienda Ospedaliera S Maria, Terni, Italy. 16. Erasmus Medical Center, Rotterdam, Netherlands. 17. 3rd Department of Medicine, Cardiology and Intensive Care Medicine, Wilhelminenhospital and Sigmund Freud University, Medical Faculty, Vienna, Austria. 18. Onze Lieve vrouwe Gasthuis, Amsterdam, Netherlands. 19. Erasmus Medical Center, Rotterdam, Netherlands; Academic Medical Center of Amsterdam, Amsterdam, Netherlands. Electronic address: patrick.w.j.c.serruys@gmail.com. 20. Department of Cardiology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland. Electronic address: stephan.windecker@insel.ch.
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.
RCT Entities:
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.
Authors: Mariusz Tomaniak; Ply Chichareon; Yoshinobu Onuma; Efthymios N Deliargyris; Kuniaki Takahashi; Norihiro Kogame; Rodrigo Modolo; Chun Ching Chang; Tessa Rademaker-Havinga; Robert F Storey; George D Dangas; Deepak L Bhatt; Dominick J Angiolillo; Christian Hamm; Marco Valgimigli; Stephan Windecker; Philippe Gabriel Steg; Pascal Vranckx; Patrick W Serruys Journal: JAMA Cardiol Date: 2019-11-01 Impact factor: 14.676
Authors: Safi U Khan; Mohammed Osman; Muhammad U Khan; Muhammad Shahzeb Khan; Di Zhao; Mamas A Mamas; Nazir Savji; Ahmad Al-Abdouh; Rani K Hasan; Erin D Michos Journal: Ann Intern Med Date: 2020-03-17 Impact factor: 25.391