Author + information
- Received April 3, 2017
- Revision received May 31, 2017
- Accepted June 1, 2017
- Published online August 21, 2017.
- Raffaele Piccolo, MDa,
- Fausto Feres, MDb,
- Alexandre Abizaid, MDb,
- Martine Gilard, MDc,
- Marie-Claude Morice, MDc,
- Myeong-Ki Hong, MD, PhDd,
- Hyo-Soo Kim, MD, PhDe,
- Antonio Colombo, MDf,
- Deepak L. Bhatt, MD, MPHg,
- Tullio Palmerini, MDh,
- Gregg W. Stone, MDi,j,
- Stephan Windecker, MDa and
- Marco Valgimigli, MD, PhDa,∗ ()
- aDepartment of Cardiology, University Hospital of Bern, University of Bern, Switzerland
- bInstituto Dante Pazzanese de Cardiologia, São Paulo, Brazil
- cDepartment of Cardiology, CHU de la Cavale Blanche, Brest, France
- dDivision of Cardiology, Severance Cardiovascular Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
- eDepartment of Internal Medicine, Cardiovascular Center, Seoul National University Hospital, Seoul, Republic of Korea
- fInterventional Cardiology Unit, San Raffaele Scientific Institute, Milan, Italy
- gHeart and Vascular Center, Brigham and Women’s Hospital, Harvard Medical School, Harvard University, Boston, Massachusetts
- hDipartimento Cardio-Toraco-Vascolare, University of Bologna, Bologna, Italy
- iColumbia University Medical Center/New York-Presbyterian Hospital, New York, New York
- jCardiovascular Research Foundation, New York, New York
- ↵∗Address for correspondence:
Dr. Marco Valgimigli, Department of Cardiology, University Hospital of Bern, University of Bern, 3010 Bern, Switzerland.
Objectives The study sought to evaluate the presence of a clinically relevant rebound phenomenon after dual antiplatelet therapy (DAPT) discontinuation in randomized trials.
Background It is currently unknown whether clopidogrel discontinuation after short-term DAPT is associated with an early hazard of ischemic events.
Methods The authors performed an individual participant data analysis and aggregate meta-analysis. The primary outcome was major adverse cardiac and cerebrovascular events (MACCE), defined as the composite of cardiac death, myocardial infarction (MI), or stroke.
Results The study included 11,473 PCI patients with individual participant data from 6 randomized trials comparing short-term DAPT (3 or 6 months) versus long-term DAPT (12 months or more). During the first 90 days following clopidogrel discontinuation, there was no significant increase in the risk of MACCE between patients randomized to short-term DAPT compared with long-term DAPT (hazard ratio [HR]: 1.18; 95% confidence interval [CI]: 0.71 to 1.98; p = 0.52; absolute risk difference 0.10%; 95% CI: −0.16% to 0.36%). The risk of MI or stent thrombosis was similar among patients randomized to short-term DAPT versus long-term DAPT (HR: 0.93; 95% CI: 0.46 to 1.90; p = 0.85). In the aggregate data meta-analysis of 11 trials including 38,919 patients, a higher risk of early MACCE was observed after long-term (≥12 months) DAPT duration (HR: 2.28; 95% CI: 1.69 to 3.09; p < 0.001) but not short-term (<12 months) DAPT duration (HR: 1.08; 95% CI: 0.67 to 1.74; p for interaction = 0.036).
Conclusions Among patients undergoing PCI with predominantly new-generation DES, discontinuation of clopidogrel after 3 or 6 months DAPT duration was not associated with an early increase in adverse clinical events. An early increase in MACCE was observed after long-term (≥12 months) DAPT exposure.
Dr. Piccolo has received a research grant from the Veronesi Foundation. Dr. Morice has received minor lecture fees from GE, Abbott, and Terumo. Dr. Bhatt has served on the advisory board for Cardax, Elsevier Practice Update Cardiology, Medscape Cardiology, and Regado Biosciences; has served on the board of directors for Boston VA Research Institute and Society of Cardiovascular Patient Care; has served as the Chair of the American Heart Association Quality Oversight Committee; has served on the data monitoring committee of the Duke Clinical Research Institute, Harvard Clinical Research Institute, Mayo Clinic, and Population Health Research Institute; has received honoraria from American College of Cardiology (Senior Associate Editor, Clinical Trials and News, ACC.org), Belvoir Publications (Editor in Chief, Harvard Heart Letter), Duke Clinical Research Institute (clinical trial steering committees), Harvard Clinical Research Institute (clinical trial steering committee), HMP Communications (Editor in Chief, Journal of Invasive Cardiology), Journal of the American College of Cardiology (Guest Editor; Associate Editor), Population Health Research Institute (clinical trial steering committee), Slack Publications (Chief Medical Editor, Cardiology Today’s Intervention), Society of Cardiovascular Patient Care (Secretary/Treasurer), and WebMD (CME steering committees); has served as the Deputy Editor of Clinical Cardiology; has served as the Chair of the NCDR-ACTION Registry Steering Committee and VA CART Research and Publications Committee; has received research funding from Amarin, Amgen, AstraZeneca, Bristol-Myers Squibb, Eisai, Ethicon, Forest Laboratories, Ischemix, Lilly, Medtronic, Pfizer, Roche, Sanofi, and The Medicines Company; has received royalties from Elsevier (Editor, Cardiovascular Intervention: A Companion to Braunwald’s Heart Disease); has served as the site co-investigator for Biotronik, Boston Scientific, and St. Jude Medical; has served as a trustee of the American College of Cardiology; and has performed unfunded research for FlowCo, PLx Pharma, and Takeda. Dr. Palmerini has received a speaker fee from Abbott Vascular; and a research grant from Eli Lilly. Dr. Windecker has received institutional research grants from Abbott Vascular, Biotronik, Boston Scientific, Medtronic, Edwards Lifesciences, and St. Jude Medical. Dr. Valgimigli has served on the advisory board for AstraZeneca and St. Jude Vascular; has received lecture fees from AstraZeneca, Terumo Medical, Alvimedica, St. Jude Medical, Abbott Vascular, The Medicines Company, and Correvio; has received travel support from The Medicines Company; and has received institutional grant support from AstraZeneca. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Received April 3, 2017.
- Revision received May 31, 2017.
- Accepted June 1, 2017.
- 2017 American College of Cardiology Foundation