Author + information
- Received February 4, 2020
- Revision received February 28, 2020
- Accepted March 9, 2020
- Published online May 11, 2020.
- Dominick J. Angiolillo, MD, PhDa,
- Usman Baber, MD, MSb,
- Samantha Sartori, PhDb,
- Carlo Briguori, MD, PhDc,
- George Dangas, MD, PhDb,
- David J. Cohen, MD, MScd,
- Shamir R. Mehta, MD, MSce,
- C. Michael Gibson, MDf,
- Rishi Chandiramani, MDb,
- Kurt Huber, MDg,
- Ran Kornowski, MDh,
- Giora Weisz, MDi,
- Vijay Kunadian, MBBS, MDj,
- Keith G. Oldroyd, MBChB, MD (hons)k,
- Han Ya-Ling, MD, PhDl,
- Upendra Kaul, MDm,
- Bernhard Witzenbichler, MDn,
- Dariusz Dudek, MD, PhDo,p,
- Gennaro Sardella, MDq,
- Javier Escaned, MD, PhDr,
- Samin Sharma, MDb,
- Richard A. Shlofmitz, MDs,
- Timothy Collier, MSct,
- Stuart Pocock, PhDt and
- Roxana Mehran, MDb,∗ (, )@Drroxmehran
- aDivision of Cardiology, University of Florida College of Medicine, Jacksonville, Florida
- bThe Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, New York
- cMediterranea Cardiocentro, Naples, Italy
- dUniversity of Missouri-Kansas City, Kansas City, Missouri
- ePopulation Health Research Institute, McMaster University and Hamilton Health Sciences, Hamilton, Ontario, Canada
- fDivision of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
- g3rd Department of Medicine, Cardiology and Intensive Care Medicine, Wilhelminen Hospital, and Sigmund Freud University, Medical Faculty, Vienna, Austria
- hCardiology Department, Rabin Medical Center, Petach Tikva, Israel
- iDepartment of Cardiology, Montefiore Medical Center, Bronx, New York
- jTranslational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University and Freeman Hospital, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom
- kWest of Scotland Heart and Lung Centre, Golden Jubilee National Hospital, Glasgow, United Kingdom
- lDepartment of Cardiology, General Hospital of Shenyang Military Region, Shenyang, Liaoning, China
- mBatra Hospital and Medical Research Center, New Delhi, India
- nDepartment of Cardiology and Pneumology, Helios Amper-Klinikum, Dachau, Germany
- oInstitute of Cardiology, Jagiellonian University Medical College, Krakow, Poland
- pMaria Cecilia Hospital, GVM Care & Research, Cotignola (RA), Italy
- qDepartment of Cardiology, Policlinico Umberto I, Sapienza University of Rome, Rome, Italy
- rHospital Clínico San Carlos IDISCC, Complutense University of Madrid, Madrid, Spain
- sSt. Francis Hospital, Roslyn, New York
- tDepartment of Medical Statistics, London School of Hygiene and Tropical Medicine, London, United Kingdom
- ↵∗Address for correspondence:
Dr. Roxana Mehran, Center for Interventional Cardiovascular Research and Clinical Trials, The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1030, New York, New York 10029-6574.
Background P2Y12 inhibitor monotherapy with ticagrelor after a brief period of dual antiplatelet therapy can reduce bleeding without increasing ischemic harm after percutaneous coronary intervention (PCI). The impact of this approach among patients with diabetes mellitus (DM) remains unknown.
Objectives The purpose of this study was to examine the effect of ticagrelor monotherapy versus ticagrelor plus aspirin among patients with DM undergoing PCI.
Methods This was a pre-specified analysis of the DM cohort in the TWILIGHT (Ticagrelor With Aspirin or Alone in High-Risk Patients after Coronary Intervention) trial. After 3 months of ticagrelor plus aspirin, patients were maintained on ticagrelor and randomized to aspirin or placebo for 1 year. The primary endpoint was Bleeding Academic Research Consortium 2, 3, or 5 bleeding. The composite ischemic endpoint was all-cause death, myocardial infarction, or stroke.
Results Patients with DM comprised 37% (n = 2,620) of the randomized cohort and were characterized by more frequent comorbidities and a higher prevalence of multivessel disease. The incidence of Bleeding Academic Research Consortium 2, 3, or 5 bleeding was 4.5% and 6.7% among patients with DM randomized to ticagrelor plus placebo versus ticagrelor plus aspirin (hazard ratio: 0.65; 95% confidence interval: 0.47 to 0.91; p = 0.012). Ticagrelor monotherapy was not associated with an increase in ischemic events compared with ticagrelor plus aspirin (4.6% vs. 5.9%; hazard ratio: 0.77; 95% confidence interval: 0.55 to 1.09; p = 0.14). In the overall trial population, there was no significant interaction between DM status and treatment group for the primary bleeding or ischemic endpoints.
Conclusions Compared with ticagrelor plus aspirin, the effect of ticagrelor monotherapy in reducing the risk of clinically relevant bleeding without any increase in ischemic events was consistent among patients with or without DM undergoing PCI. (Ticagrelor With Aspirin or Alone in High-Risk Patients After Coronary Intervention [TWILIGHT]; NCT02270242)
This work is supported by an investigator-initiated grant from AstraZeneca. Dr. Angiolillo has received grant support, consulting fees, and honoraria from Amgen, Aralez, Bayer, Biosensors, Boehringer Ingelheim, Bristol-Myers Squibb, Chiesi, Daiichi-Sankyo, Eli Lilly, Janssen, Merck, and Sanofi; has received consulting fees and honoraria from Haemonetics, PhaseBio, PLx Pharma, Pfizer, and The Medicines Company; has received grant support and fees for review activities from CeloNova; has received fees for review activities from St. Jude Medical; and has received grant support from CSL Behring, Eisai, Gilead, Idorsia Pharmaceuticals, Matsutani Chemical Industry, Novartis, Osprey Medical, RenalGuard Solutions, and the Scott R. MacKenzie Foundation. Dr. Baber has received honoraria from AstraZeneca, Boston Scientific, and Amgen; and has received a grant from AstraZeneca. Dr. Dangas has received research grants to his institution from AstraZeneca, Abbott, Boston Scientific, Medtronic, Bayer, and Daiichi-Sankyo; has received Advisory Board fees from Abbott, Boston Scientific, and Sanofi; has served as a consultant for Merck, CSL Behring, Bayer, Biosensors, and Daiichi-Sankyo; and has previously held stock in Medtronic. Dr. Cohen has received grant support, paid to his institution, and consulting fees from AstraZeneca, Medtronic, Abbott Vascular, and Boston Scientific; and has received grant support, paid to his institution, from AstraZeneca. Dr. Mehta has received grant support from, served on an executive committee, and served as site investigator for AstraZeneca; and has received a research grant from Boston Scientific. Dr. Gibson has received grant support and consulting fees from Angel Medical, Bayer, CSL Behring, Janssen Pharmaceuticals, Johnson & Johnson, and Portola Pharmaceuticals; has received consulting fees from The Medicines Company, AstraZeneca, Eli Lilly, Gilead Sciences, Novo Nordisk, WebMD, UpToDate Cardiovascular Medicine, Amarin Pharma, Amgen, Boehringer Ingelheim, Chiesi, Merck, PharmaMar, Sanofi, Somahlution, Verreseon Corporation, Boston Scientific, Impact Bio, MedImmume, Medtelligence, MicroPort, PERT Consortium, and GE Healthcare; has held equity in nference; has served as chief executive officer of Baim Institute; and has received grant support, paid to Baim Institute, from Bristol-Myers Squibb. Dr. Huber has received lecture fees from AstraZeneca and Bayer. Dr. Weisz has received grant support and Advisory Board fees from Corindus; has received Advisory Board fees from and held equity in Filterlex; has served on the Advisory Board for and held options in Trisol, Magenta, and Intratech; and has received institutional grant support from Abbott, Ancora, CSI, and ShockWave. Dr. Kunadian has received consulting fees/honoraria from Bayer, Amgen, Daiichi-Sankyo, Abbott Vascular, and AstraZeneca; and has received a major institutional research grant from AstraZeneca. Dr. Oldroyd has received grant support and lecture fees from AstraZeneca; and has received lecture fees from Biosensors, Abbott Vascular, and GE. Dr. Escaned has received consulting fees and lecture fees from Abbott, Philips, Boston Scientific, and Medtronic; and has received lecture fees from Abiomed, Terumo, and Biosensors. Dr. Sharma has served on the Speakers Bureau for Abbott Vascular, Boston Scientific, and Cardiovascular Systems; and has served on the Advisory Board of Boston Scientific. Dr. Collier has served on Data Monitoring Committees sponsored by AstraZeneca, Boston Scientific, Daiichi-Sankyo, Devax, Infraredx, Medtronic, Pfizer, and Zoll. Dr. Pocock has received research grants and consultancy honoraria from AstraZeneca. Dr. Mehran has received consulting fees from Abbott Vascular, Boston Scientific, Medscape/WebMD, Siemens Medical Solutions, Phillips/Volcano/Spectranetics, Roviant Sciences, Sanofi Italy, Bracco Group, Janssen, and AstraZeneca; has received grant support, paid to her institution, from Bayer, CSL Behring, DSI, Medtronic, Novartis Pharmaceuticals, OrbusNeich, Osprey Medical, PLC/RenalGuard, and Abbott Vascular; has received grant support and Advisory Board fees, paid to her institution, from Bristol-Myers Squibb; has received fees for serving on a Data and Safety Monitoring Board from Watermark Research Funding; has received advisory fees and lecture fees from Medintelligence (Janssen); and has received lecture fees from Bayer. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Patrick W. Serruys, MD, PhD, served as Guest Associate Editor for this paper.
The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the JACC author instructions page.
- Received February 4, 2020.
- Revision received February 28, 2020.
- Accepted March 9, 2020.
- 2020 American College of Cardiology Foundation
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