Author + information
- Received May 2, 2019
- Revision received August 8, 2019
- Accepted August 10, 2019
- Published online October 28, 2019.
- Anna Franzone, MD, PhDa,
- Eugène McFadden, MDb,c,
- Sergio Leonardi, MD, MHSd,
- Raffaele Piccolo, MD, PhDa,
- Pascal Vranckx, MD, PhDe,
- Patrick W. Serruys, MD, PhDf,
- Edouard Benit, MDg,
- Christoph Liebetrau, MDh,i,
- Luc Janssens, MDj,
- Maurizio Ferrario, MDd,
- Aleksander Zurakowski, MDk,
- Roberto Diletti, MD, PhDl,
- Marcello Dominici, MDm,
- Kurt Huber, MDn,
- Ton Slagboom, MDo,
- Paweł Buszman, MDp,q,
- Leonardo Bolognese, MDr,
- Carlo Tumscitz, MDs,
- Krzysztof Bryniarski, MD, PhDt,
- Adel Aminian, MDu,
- Mathias Vrolix, MDv,
- Ivo Petrov, MDw,
- Scot Garg, MD, PhDx,
- Christoph Naber, MDy,
- Janusz Prokopczuk, MDz,
- Christian Hamm, MDi,aa,
- Philippe Gabriel Steg, MDbb,
- Dik Heg, PhDcc,
- Peter Jüni, MDdd,
- Stephan Windecker, MDee,
- Marco Valgimigli, MD, PhDee,∗ (, )@vlgmrc,
- for the GLASSY Investigators
- aDepartment of Advanced Biomedical Sciences, Federico II University of Naples, Naples, Italy
- bCardialysis Core Laboratories and Clinical Trial Management, Rotterdam, the Netherlands
- cDepartment of Cardiology, Cork University Hospital, Cork, Ireland
- dUniversity of Pavia and Fondazione IRCCS Policlinico S. Matteo, Pavia, Italy
- eDepartment of Cardiology and Critical Care Medicine, Hartcentrum Hasselt, Jessa Ziekenhuis, Belgium
- fDepartment of Cardiology, Imperial College of London, London, United Kingdom
- gDepartment of Cardiology, Jessa Hospital, Hasselt, Belgium
- hDepartment of Cardiology, Kerckhoff Heart and Thorax Center, Bad Nauheim, Germany
- iGerman Center for Cardiovascular Research (DZHK), partner site RheinMain, Frankfurt am Main, Germany
- jImelda Hospital, Bonheiden, Belgium
- kDepartment of Interventional Cardiology, American Heart of Poland SA, Chrzanów, Poland
- lThoraxcenter, Erasmus Medical Center, Rotterdam, the Netherlands
- mS. Maria University-Hospital, Terni, Italy
- n3rd Medical Department, Cardiology, Wilhelminenhospital, and Sigmund Freud University Medical School, Vienna, Austria
- oOnze Lieve Vrouwe Gasthuis Amsterdam, Amsterdam, the Netherlands
- pCenter for Cardiovascular Research and Development, American Heart of Poland, Sanatoryjna 1, Ustroń, Poland
- qDepartment of Epidemiology and Statistics, Medical University of Silesia, Poniatowskiego 15, Katowice
- rAzienda Toscana Usl Sudest, Arezzo, Italy
- sCardiology Unit Sant'Anna Hospital, Ferrara, Italy
- tJagiellonian University Medical College, The John Paul II Hospital, Krakow, Poland
- uDepartment of Cardiology, Centre Hospitalier Universitaire de Charleroi, Charleroi, Belgium
- vZiekenhuis Oost Limburg, Genk, Belgium
- wAcibadem City Clinic Cardiovascular Center, Sofia, Bulgaria
- xEast Lancashire Hospitals NHS Trust, Blackburn, United Kingdom
- yContilia Heart and Vascular Centre, Stadtspital Triemli, Zürich, Switzerland
- zPolsko-Amerykańskie Kliniki Serca Kozle, Kozle, Poland
- aaDepartment of Cardiology, Kerckhoff Heart and Thorax Center, Bad Nauheim, Germany
- bbHôpital Bichat, AP-HP, Université Paris-Diderot, Paris, France
- ccInstitute of Social and Preventive Medicine and Clinical Trials Unit, University of Bern, Bern, Switzerland
- ddApplied Health Research Centre, Li Ka Shing Knowledge Institute of St. Michael's Hospital, Department of Medicine, University of Toronto, Toronto, Ontario, Canada
- eeDepartment of Cardiology, Inselspital, University of Bern, Bern, Switzerland
- ↵∗Address for correspondence:
Prof. Marco Valgimigli, Swiss Cardiovascular Center Bern, Bern Inselspital, University of Bern, Bern University Hospital, CH-3010 Bern, Switzerland.
Background The GLOBAL LEADERS (GLOBAL LEADERS: A Clinical Study Comparing Two Forms of Anti-platelet Therapy After Stent Implantation) study randomly assigned 15,991 patients undergoing percutaneous coronary intervention to 1-month dual antiplatelet therapy (DAPT) followed by 23-month ticagrelor monotherapy or conventional 12-month DAPT followed by 12-month aspirin. Apart from Q-wave myocardial infarction (MI), all study endpoints were analyzed as investigator reported.
Objectives This was a pre-specified ancillary study assessing whether experimental therapy is noninferior, and if met, superior, to conventional treatment for the coprimary efficacy endpoint of all-cause death, nonfatal MI, nonfatal stroke, or urgent target vessel revascularization and superior in preventing BARC 3 (Bleeding Academic Research Consortium) or 5 bleeding (coprimary safety endpoint) at 2 years with a 0.025 significance level to preserve nominal 5% alpha error.
Methods An independent clinical event committee adjudicated investigator-reported and eventually unreported events of 7,585 patients from the 20 top-enrolling participating sites.
Results The 2-year coprimary efficacy endpoint occurred in 271 (7.14%) and in 319 (8.41%) patients in the experimental and conventional groups, respectively (rate ratio [RR]: 0.85; 95% confidence interval [CI]: 0.72 to 0.99), fulfilling noninferiority (p noninferiority <0.001), but not superiority (p superiority = 0.0465). The rates of BARC 3 or 5 bleeding did not differ (RR: 1.00; 95% CI: 0.75 to 1.33; p = 0.986). A time-dependent treatment effect was observed with the experimental strategy being associated with a lower risk of MI (RR: 0.54; 95% CI: 0.33 to 0.88; p interaction = 0.062) and definite stent thrombosis (RR: 0.14; 95% CI: 0.03 to 0.63; p interaction = 0.007) after 1-year post-percutaneous coronary intervention.
Conclusions Ticagrelor monotherapy after 1-month DAPT was noninferior, but not superior, to conventional treatment in the prevention of ischemic events, and it did not decrease major bleeding risk as compared with conventional treatment. (GLOBAL LEADERS Adjudication Sub-Study [GLASSY]; NCT03231059).
Dr. McFadden has received personal fees and nonfinancial support from the University of Bern and Daiichi-Sankyo Europe; and has received travel grants from AstraZeneca and Menarini Ireland. Dr. Leonardi has received grants from AstraZeneca; and has received personal fees from AstraZeneca, Bayer, Chiesi, and Bristol-Myers Squibb/Pfizer. Dr. Vranckx has received personal fees from AstraZeneca, The Medicines Company, Terumo, CLS Behring, Daiichi-Sankyo, and Bayer Health Care. Dr. Serruys has received personal fees from Abbott, Biosensors, Cardialysis, Medtronic, Sinomedical Sciences, Philips/Volcano, Xeltis, and HeartFlow; and has received consultancy fees from Abbott Laboratories, Biosensors, Cardialysis, Medtronic, Sino Medical Sciences Technology, Philips/Volcano, Xeltis, and HeartFlow. Dr. Diletti has received grants from AstraZeneca. Dr. Naber has received personal fees from Abbott, Medtronic, Biosensors, and Biotronik. Dr. Hamm has received personal fees from and served on an Advisory Board for AstraZeneca. Dr. Steg has received grants from Bayer/Janssen, Merck, Sanofi, Servier, and Amarin; and has received consulting, speaking, or other personal fees from Merck, Sanofi, Amarin, Amgen, Bayer/Janssen, Servier, Bristol-Myers Squibb, Idorsia, Boehringer Ingelheim, Pfizer, Novartis, Regeneron, Eli Lilly, Novartis, Novo-Nordisk, AstraZeneca, and Servier. Dr. Jüni serves as an unpaid member of the steering group of trials funded by AstraZeneca, Biotronik, Biosensors, St. Jude Medical, and The Medicines Company; and has received research grants paid to his institution from AstraZeneca, Biotronik, Biosensors International, Eli Lilly and The Medicines Company; and has received and honoraria to the institution for participation in advisory boards from Amgen, but has not received personal payments by any pharmaceutical company or device manufacturer. Dr. Windecker has received grants from Amgen, Abbott, Biotronik, Bristol-Myers Squibb, Boston Scientific, Medtronic, Bayer, Edwards Lifesciences, St. Jude Medical, Terumo, Sinomed, and Polares. Dr. Valgimigli has received grants from Abbott, Medicure, Terumo, and AstraZeneca; and has received speaker fees and personal fees from Chiesi, Bayer, Daiichi-Sankyo, Amgen, Terumo, Alvimedica, AstraZeneca, Biosensors, and Idorsia. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Received May 2, 2019.
- Revision received August 8, 2019.
- Accepted August 10, 2019.
- 2019 American College of Cardiology Foundation
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