Author + information
- Received February 5, 2020
- Revision received March 5, 2020
- Accepted March 9, 2020
- Published online May 11, 2020.
- George Dangas, MD, PhDa,
- Usman Baber, MD, MSa,
- Samin Sharma, MDa,
- Gennaro Giustino, MDa,
- Shamir Mehta, MD, MScb,
- David J. Cohen, MD, MScc,
- Dominick J. Angiolillo, MD, PhDd,
- Samantha Sartori, PhDa,
- Rishi Chandiramani, MDa,
- Carlo Briguori, MD, PhDe,
- Dariusz Dudek, MD, PhDf,g,
- Javier Escaned, MD, PhDh,
- Kurt Huber, MDi,
- Timothy Collier, MScj,
- Ran Kornowski, MDk,
- Vijay Kunadian, MBBS, MDl,
- Upendra Kaul, MDm,
- Keith Oldroyd, MBChB, MD (hons)n,
- Gennaro Sardella, MDo,
- Richard Shlofmitz, MDp,
- Bernhard Witzenbichler, MDq,
- Han Ya-Ling, MD, PhDr,
- Stuart Pocock, PhDj,
- C. Michael Gibson, MDs and
- Roxana Mehran, MDa,∗ (, )@Drroxmehran
- aThe Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, New York
- bPopulation Health Research Institute, McMaster University and Hamilton Health Sciences, Hamilton, Ontario, Canada
- cUniversity of Missouri-Kansas City, Kansas City, Missouri
- dDivision of Cardiology, University of Florida College of Medicine, Jacksonville, Florida
- eMediterranea Cardiocentro, Naples, Italy
- fInstitute of Cardiology, Jagiellonian University Medical College, Krakow, Poland
- gMaria Cecilia Hospital, GVM Care & Research, Cotignola (RA), Italy
- hHospital Clínico San Carlos IDISCC, Complutense University of Madrid, Madrid, Spain
- i3rd Department of Medicine, Cardiology and Intensive Care Medicine, Wilhelminen Hospital, and Sigmund Freud University, Medical Faculty, Vienna, Austria
- jDepartment of Medical Statistics, London School of Hygiene and Tropical Medicine, London, United Kingdom
- kCardiology Department, Rabin Medical Center, Petach Tikva, Israel
- lTranslational 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
- mBatra Hospital and Medical Research Center, New Delhi, India
- nWest of Scotland Heart and Lung Centre, Golden Jubilee National Hospital, Glasgow, United Kingdom
- oDepartment of Cardiology, Policlinico Umberto I, Sapienza University of Rome, Rome, Italy
- pSt. Francis Hospital, Roslyn, New York
- qDepartment of Cardiology and Pneumology, Helios Amper-Klinikum, Dachau, Germany
- rDepartment of Cardiology, General Hospital of Shenyang Military Region, Shenyang, Liaoning, China
- sDivision of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
- ↵∗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 Whether a regimen of ticagrelor monotherapy attenuates bleeding complications without increasing ischemic risk in patients undergoing complex percutaneous coronary intervention (PCI) is unknown.
Objectives The purpose of this study was to evaluate the effect of ticagrelor monotherapy versus ticagrelor plus aspirin in patients undergoing complex PCI from the randomized, double-blind, placebo-controlled TWILIGHT (Ticagrelor with Aspirin or Alone in High-Risk Patients after Coronary Intervention) trial.
Methods In the TWILIGHT trial, after 3 months of ticagrelor plus aspirin, event-free and adherent patients remained on ticagrelor and were randomly assigned to receive aspirin or placebo for 1 year. Complex PCI was defined as any of the following: 3 vessels treated, ≥3 lesions treated, total stent length >60 mm, bifurcation with 2 stents implanted, atherectomy device use, left main PCI, surgical bypass graft or chronic total occlusion as target lesions. Bleeding and ischemic endpoints were evaluated at 1 year after randomization.
Results Among 7,119 patients randomized in the main trial, complex PCI was performed in 2,342 patients. Compared to ticagrelor plus aspirin, ticagrelor plus placebo resulted in significantly lower rates of Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 bleeding (4.2% vs. 7.7%; hazard ratio [HR]: 0.54; 95% confidence interval [CI]: 0.38 to 0.76). BARC type 3 or 5 bleeding was also significantly reduced (1.1% vs. 2.6%; HR: 0.41; 95% CI: 0.21 to 0.80). There were no significant between-group differences in death, myocardial infarction, or stroke (3.8% vs. 4.9%; HR: 0.77; 95% CI: 0.52 to 1.15), nor in stent thrombosis.
Conclusions Among patients undergoing complex PCI who initially completed 3 months of ticagrelor plus aspirin, continuation of ticagrelor monotherapy was associated with lower incidence of bleeding without increasing the risk of ischemic events compared to continuing ticagrelor plus aspirin. (Ticagrelor With Aspirin or Alone in High-Risk Patients After Coronary Intervention [TWILIGHT]; NCT02270242)
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. Baber has received honoraria from AstraZeneca, Boston Scientific, and Amgen; and has received a grant from AstraZeneca. Dr. Giustino has received consultant fees (Advisory Board) for Bristol-Myers Squibb/Pfizer. 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. 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. 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, and RenalGuard Solutions. 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. Huber has received lecture fees from AstraZeneca and Bayer. 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. 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. 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 5, 2020.
- Revision received March 5, 2020.
- Accepted March 9, 2020.
- 2020 American College of Cardiology Foundation
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