Author + information
- Received June 24, 2019
- Revision received August 1, 2019
- Accepted August 1, 2019
- Published online October 14, 2019.
- Kuniaki Takahashi, MDa,
- Patrick W. Serruys, MD, PhDb,∗ (, )@kuniaki_0125,
- Ply Chichareon, MDa,c,
- Chun Chin Chang, MDd,
- Mariusz Tomaniak, MDd,e,
- Rodrigo Modolo, MDa,f,
- Norihiro Kogame, MDa,
- Michael Magro, MD, PhDg,
- Saqib Chowdhary, MD, PhDh,
- Ingo Eitel, MDi,
- Robert Zweiker, MDj,
- Paul Ong, MDk,
- Michael Mundt Ottesen, MD, PhDl,
- Jan G.P. Tijssen, PhDa,m,
- Joanna J. Wykrzykowska, MD, PhDa,
- Robbert J. de Winter, MD, PhDa,
- Scot Garg, MD, PhDn,
- Hans-Peter Stoll, MDo,
- Christian Hamm, MDp,
- Philippe Gabriel Steg, MDq,
- Yoshinobu Onuma, MD, PhDd,m,
- Marco Valgimigli, MD, PhDr,
- Pascal Vranckx, MD, PhDs,
- Didier Carrie, MDt and
- Stephan Windecker, MDr
- aAcademic Medical Center, University of Amsterdam, Amsterdam, the Netherlands
- bInternational Centre for Circulatory Health, Imperial College London, London, United Kingdom
- cDivision of Cardiology, Department of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Songkhla, Thailand
- dDepartment of Cardiology, Thoraxcenter, Erasmus Medical Center, Rotterdam, the Netherlands
- eFirst Department of Cardiology, Medical University of Warsaw, Warsaw, Poland
- fDepartment of Internal Medicine, Cardiology Division, University of Campinas (UNICAMP), Campinas, Brazil
- gTweeSteden Ziekenhuis, Tilburg, the Netherlands
- hManchester University Foundation Trust, Manchester, United Kingdom
- iUniversity Heart Center Lübeck, Medical Clinic II (Cardiology/Angiology/Intensive Care Medicine) and German Center for Cardiovascular Research (DZHK), partner site Hamburg/Kiel/Lübeck, Lübeck, Germany
- jMedical University Hospital Graz, Graz, Austria
- kTan Tock Seng Hospital, Singapore
- lZealand University Hospital, Roskilde, Denmark
- mCardialysis B.V., Rotterdam, the Netherlands
- nRoyal Blackburn Hospital, Blackburn, United Kingdom
- oBiosensors Clinical Research, Morges, Switzerland
- pUniversity of Giessen and Kerckhoff Heart and Thorax Center, University of Giessen, Bad Nauheim, Germany
- qFACT (French Alliance for Cardiovascular Trials), Université Paris-Diderot, Paris, France
- rDepartment of Cardiology, University of Bern, Inselspital, Bern, Switzerland
- sJessa Ziekenhuis, Faculty of Medicine and Life Sciences at the Hasselt University, Hasselt, Belgium
- tRangueil Hospital, Toulouse, France
- ↵∗Address for correspondence:
Dr. Patrick W. Serruys, Erasmus University Medical Center, P.O. Box 2125, 3000 CC Rotterdam, the Netherlands.
Background Data on optimal antiplatelet treatment regimens in patients who undergo multivessel percutaneous coronary intervention (PCI) are sparse.
Objectives This post hoc study investigated the impact of an experimental strategy (1-month dual antiplatelet therapy [DAPT] followed by 23-month ticagrelor monotherapy) versus a reference regimen (12-month DAPT followed by 12-month aspirin monotherapy) according to multivessel PCI.
Methods The GLOBAL LEADERS trial is a prospective, multicenter, open-label, randomized controlled trial, allocating all-comer patients in a 1:1 ratio to either the experimental strategy or the reference regimen. The primary endpoint was the composite of all-cause death or new Q-wave myocardial infarction at 2 years. The secondary safety endpoint was Bleeding Academic Research Consortium type 3 or 5 bleeding.
Results Among the overall study population (n=15,845), 3,576 patients (22.4%) having multivessel PCI experienced a significantly higher risk of ischemic and bleeding events at 2 years, compared to those having single-vessel PCI. There was an interaction between the experimental strategy and multivessel PCI on the primary endpoint (hazard ratio: 0.62; 95% confidence interval: 0.44 to 0.88; pinteraction = 0.031). This difference was largely driven by a lower risk of all-cause mortality. In contrast, the risk of Bleeding Academic Research Consortium type 3 or 5 bleeding was statistically similar between the 2 regimens (hazard ratio: 0.92; 95% confidence interval: 0.61 to 1.39; pinteraction = 0.754).
Conclusions Long-term ticagrelor monotherapy following 1-month DAPT can favorably balance ischemic and bleeding risks in patients with multivessel PCI. These findings should be interpreted as hypothesis-generating and need to be replicated in future dedicated randomized trials. (GLOBAL LEADERS: A Clinical Study Comparing Two Forms of Anti-platelet Therapy After Stent Implantation; NCT01813435).
- drug-eluting stent
- dual antiplatelet therapy
- multivessel percutaneous coronary intervention
- ticagrelor monotherapy
The Global Leaders trial was supported by unrestricted grants from AstraZeneca, Biosensors, and The Medicines Company. ECRI (European Cardiovascular Research Institute) was formally the sponsor of the study. Dr. Serruys has received personal fees from Abbott 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. Dr. Chichareon has received a research grant from Biosensors. Dr. Tomaniak has received lecture fees from AstraZeneca. Dr. Modolo has received research grants from the Sao Paulo Research Foundation (FAPESP grant number 2017/22013-8), Biosensors, and SMT. Dr. Eitel has received personal fees from AstraZeneca, Bayer, and Edwards Lifesciences. Dr. de Winter has received an unrestricted educational research grant from AstraZeneca for the Academic Medical Center, University of Amsterdam. Dr. Tijssen has received personal fees from Cardialysis for Data Safety Monitoring Board membership of the ‘Global Leaders' trial. Dr. Stoll is a full-time employee of Biosensors International. Dr. Hamm has received personal fees from AstraZeneca. Dr. Steg has received grants and personal fees from Bayer/Janssen, Merck, Sanofi, Amarin, and Servier; and has received personal fees from Amgen, Bristol-Myers Squibb, Boehringer Ingelheim, Idorsia, Pfizer, Novartis, Novo Nordisk, Regeneron, Lilly, and AstraZeneca. Dr. Valgimigli has received grants and personal fees from Abbott, Terumo, and AstraZeneca; has received personal fees from Chiesi, Bayer, Daiichi-Sankyo, Amgen, Biosensors, and Idorsia; and has received grants from Medicure. Dr. Vranckx has received personal fees from AstraZeneca and The Medicines Company; and has received personal fees from Bayer Health Care, Daiichi-Sankyo, Terumo, and CLS Behring. Dr. Windecker has received grants from Amgen, Abbott, Biotronik, Bristol-Myers Squibb, Boston Scientific, Medtronic, Edwards Lifesciences, Bayer, St. Jude, and Terumo. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Jean-Philippe Collet, MD, served as Guest Associate Editor for this paper.
Listen to this manuscript's audio summary by Editor-in-Chief Dr. Valentin Fuster on JACC.org.
- Received June 24, 2019.
- Revision received August 1, 2019.
- Accepted August 1, 2019.
- 2019 American College of Cardiology Foundation
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