Author + information
- Received December 7, 2016
- Revision received February 6, 2017
- Accepted February 12, 2017
- Published online May 1, 2017.
- Eric A. Secemsky, MD, MSca,b,c,d,
- Robert W. Yeh, MD, MScc,d,
- Dean J. Kereiakes, MDe,
- Donald E. Cutlip, MDc,
- P. Gabriel Steg, MDf,g,
- Joseph M. Massaro, PhDc,
- Patricia K. Apruzzese, MAc,
- Laura Mauri, MD, MScb,c,∗ (, )
- Dual Antiplatelet Therapy Study Investigators
- aDivision of Cardiology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts
- bDivision of Cardiology and Center for Clinical Biometrics, Department of Medicine, Brigham and Women’s Hospital, Boston, Massachusetts
- cBaim Institute for Clinical Research, Boston, Massachusetts
- dSmith Center for Outcomes Research in Cardiology, Beth Israel Deaconess Medical Center, Boston, Massachusetts
- eThe Christ Hospital Heart and Vascular Center and The Lindner Center for Research and Education, Cincinnati, Ohio
- fUniversité Paris-Diderot, INSERM U-1148, Hôpital Bichat, Département Hospitalo-Universitaire Fibrosis, Inflammation, and Remodelling, Assistance Publique–Hôpitaux de Paris, Paris, France
- gNational Heart and Lung Institute, Institute of Cardiovascular Medicine and Science, Royal Brompton Hospital, Imperial College, London, United Kingdom
- ↵∗Address for correspondence:
Dr. Laura Mauri, Division of Cardiology, Harvard Medical School, Brigham and Women’s Hospital, 75 Francis Street, Boston, Massachusetts 02115.
Objectives This study sought to determine whether patients with peripheral arterial disease (PAD) experience different reductions in ischemic event and increases in bleeding events with extended duration dual antiplatelet therapy versus those without PAD.
Background Patients with PAD have increased ischemic and bleeding risks after coronary stenting.
Methods The DAPT (Dual Antiplatelet Therapy) study randomized 11,648 patients free from ischemic and bleeding events 12 months after coronary stenting to continued thienopyridine plus aspirin therapy for an additional 18 months versus aspirin therapy alone. The effects of continued thienopyridine on myocardial infarction (MI) or stent thrombosis, major adverse cardiovascular and cerebrovascular events (death, MI, or stroke) and bleeding (GUSTO [Global Utilization of t-PA and Streptokinase for Occluded Coronary Arteries] moderate or severe) were assessed among those with versus without PAD.
Results Among 11,648 randomized patients, 649 (5.57%) had PAD. Between 12 and 30 months, randomized patients with PAD had higher rates of MI/stent thrombosis (6.03% vs. 2.92%; p < 0.001), major adverse cardiovascular and cerebrovascular events (11.65% vs. 4.62%; p < 0.001), and bleeding (4.86% vs. 1.74%; p < 0.001). Continued thienopyridine versus placebo was associated with consistent treatment effects for MI/stent thrombosis (with PAD, HR: 0.63; 95% CI: 0.32 to 1.22; without PAD, HR: 0.53; 95% CI: 0.42, 0.66; interaction p = 0.631), major adverse cardiovascular and cerebrovascular events (with PAD, HR: 1.06; 95% CI: 0.67 to 1.67; without PAD, HR: 0.70; 95% CI: 0.59 to 0.84; interaction p = 0.103), and bleeding (with PAD, HR, 1.82; 95% CI: 0.87 to 3.83; without PAD, HR: 1.66; 95% CI: 1.23 to 2.24; interaction p = 0.811).
Conclusions Among patients undergoing coronary stenting, those with PAD have more ischemic and bleeding events versus those without PAD. Extended duration dual antiplatelet therapy is associated with consistent ischemic benefit and bleeding harm among patients with and without PAD.
Sponsored by the Baim Institute for Clinical Research (formerly known as Harvard Clinical Research Institute); and supported by the National Heart, Lung and Blood Institute (K23 HL 118138), Abbott, Boston Scientific Corporation, Cordis Corporation, Medtronic, Inc., Bristol-Myers Squibb Company/Sanofi Pharmaceuticals Partnership, Eli Lilly and Company, and Daiichi Sankyo Company Limited, and the U.S. Department of Health and Human Services (1RO1FD003870-01).
Dr. Yeh has received research grants from Abiomed and Boston Scientific; and advisory board/consulting for Abbott and Boston Scientific. Dr. Kereiakes has received research funding and consultant to Abbott Vascular, Boston Scientific, and Sanofi. Dr. Cutlip has received grant funding from Medtronic, Boston Scientific, and Celonova. Dr. Steg has received research grants from Merck, Sanofi, and Servier; and speaking or consulting fees from Amarin, AstraZeneca, Bayer, Boehringer-Ingelheim, Bristol-Myers Squibb, CSL-Behring, Daiichi Sankyo, GlaxoSmithKline, Janssen, Lilly, Merck Novartis, Pfizer, Regeneron, Sanofi, Servier, and The Medicines Company. Dr. Massaro has received personal fees from Baim Institute for Clinical Research. Dr. Mauri has received grants from Abbott, Boston Scientific, Cordis, Medtronic, Eli Lilly/Daiichi Sankyo, and Sanofi/Bristol-Myers Squibb, during the conduct of the study; outside the submitted work she reports consulting fees from Amgen and St. Jude Medical; serves on the steering committee for Biotronik and Corvia; is a lecturer for AstraZeneca, Sanofi, Daiichi-Sankyo; and is an investigator for Boehringer Ingelheim and ReCor. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Received December 7, 2016.
- Revision received February 6, 2017.
- Accepted February 12, 2017.
- 2017 American College of Cardiology Foundation