Author + information
- Received October 19, 2016
- Revision received January 25, 2017
- Accepted February 10, 2017
- Published online April 17, 2017.
- Tullio Palmerini, MDa,
- Letizia Bacchi Reggiani, MStata,
- Diego Della Riva, MDa,
- Mattia Romanello, MDa,
- Fausto Feres, MDb,
- Alexandre Abizaid, MDb,
- Martine Gilard, MDc,
- Marie-Claude Morice, MDd,
- Marco Valgimigli, MD, PhDe,
- Myeong-Ki Hong, MD, PhDf,
- Byeong-Keuk Kim, MD, PhDf,
- Yangsoo Jang, MD, PhDf,
- Hyo-Soo Kim, MD, PhDg,
- Kyung Woo Park, MDg,
- Antonio Colombo, MDh,
- Alaide Chieffo, MDh,
- Jung-Min Ahn, MDi,
- Seung-Jung Park, MDi,
- Stefanie Schüpke, MDj,
- Adnan Kastrati, MDj,
- Gilles Montalescot, MDk,
- Philippe Gabriel Steg, MDl,
- Abdourahmane Diallo, MDm,
- Eric Vicaut, MDm,
- Gerard Helft, MDn,
- Giuseppe Biondi-Zoccai, MD, MStato,
- Bo Xu, MDp,
- Yaling Han, MDq,
- Philippe Genereux, MDr,
- Deepak L. Bhatt, MD, MPHs and
- Gregg W. Stone, MDr,∗ ()
- aDipartimento Cardio-Toraco-Vascolare, University of Bologna, Bologna, Italy
- bIstituto Dante Pazzanese de Cardiologia, São Paulo, Brazil
- cDepartment of Cardiology, Brest University, Brest, France
- dGénérale de Santé, Institut Cardiovasculaire Paris Sud, Massy, France
- eSwiss Cardiovascular Center, Bern, Switzerland
- fSeverance Cardiovascular Hospital, Yonsei University College of Medicine, Seoul, South Korea
- gDepartment of Internal Medicine, Seoul National University Hospital, Seoul, South Korea
- hSan Raffaele Scientific Institute, Milan, Italy
- iThe Heart Institute, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea
- jISAResearch Center, Deutsches Herzzentrum and Deutsches Zentrum für Herz-Kreislauf-Forschung, partner site Munich Heart Alliance, Munich, Germany
- kSorbonne Université-Paris 6, ACTION Study Group, Institut de Cardiologie, Centre Hospitalier Universitaire Pitié-Salpêtrière, Paris, France
- lHôpital Bichat, Assistance Publique–Hôpitaux de Paris, Paris, France
- mUnité de Recherche Clinique Lariboisière Saint-Louis Hôpital Fernand Widal, Assistance Publique–Hôpitaux de Paris, Paris, France
- nInstitut de Cardiologie, Hôpital Pitié-Salpêtrière, Assistance Publique–Hôpitaux de Paris, Paris, France
- oDepartment of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Latina, and Department of AngioCardioNeurology, IRCCS Neuromed, Pozzilli, Italy
- pCatheterization Laboratory, Fu Wai Hospital, National Center for Cardiovascular Diseases, Beijing, China
- qDepartment of Cardiology, General Hospital of Shenyang Military Region, Shenyang, China
- rColumbia University Medical Center/New York-Presbyterian Hospital and the Cardiovascular Research Foundation, New York, New York
- sBrigham and Women’s Hospital Heart and Vascular Center and Harvard Medical School, Boston, Massachusetts
- ↵∗Address for correspondence:
Dr. Gregg W. Stone, Columbia University Medical Center, The Cardiovascular Research Foundation, 1700 Broadway, 8th Floor, New York, New York 10019.
Background Although some randomized controlled trials (RCTs) and meta-analyses have suggested that prolonged dual-antiplatelet therapy (DAPT) may be associated with increased mortality, the mechanistic underpinnings of this association remain unclear.
Objectives The aim of this study was to analyze the associations among bleeding, mortality, and DAPT duration after drug-eluting stent implantation in a meta-analysis of RCTs.
Methods RCTs comparing different DAPT durations after drug-eluting stent placement were sought through the MEDLINE, Embase, and Cochrane databases and the proceedings of international meetings. Deaths were considered possibly bleeding related if occurring within 1 year of the episodes of bleeding. Primary analysis was by intention-to-treat. Secondary analysis was performed in a modified intention-to-treat population in which events occurring when all patients were on DAPT were excluded.
Results Individual patient data were obtained for 6 RCTs, and aggregate data were available for 12 RCTs. Patients with bleeding had significantly higher rates of mortality compared with those without, and in a time-adjusted multivariate analysis, bleeding was an independent predictor of mortality occurring within 1 year of the bleeding episode (hazard ratio: 6.93; 95% confidence interval: 4.53 to 10.60; p < 0.0001). Shorter DAPT was associated with lower rates of all-cause death compared with longer DAPT (hazard ratio: 0.85; 95% confidence interval: 0.73 to 1.00; p = 0.05), which was driven by lower rates of bleeding-related deaths with shorter DAPT compared with prolonged DAPT (hazard ratio: 0.65; 95% confidence interval: 0.43 to 0.99; p = 0.04). Mortality unrelated to bleeding was comparable between the 2 groups. Similar results were apparent in the modified intention-to-treat population.
Conclusions Bleeding was strongly associated with the occurrence of mortality within 1 year after the bleeding event. Shorter compared with longer DAPT was associated with lower risk for bleeding-related death, a finding that may underlie the lower all-cause mortality with shorter DAPT in the RCTs of different DAPT durations after DES.
Medtronic provided the data of the OPTIMIZE trial. Dr. Palmerini has received speaking fees from Abbott Vascular; and a research grant from Eli Lilly. Dr. Biondi-Zoccai has consulted for Bayer Pharma and Novartis; has lectured for Abbott Vascular, AstraZeneca, DirectFlow Medical, and St. Jude Medical; and has received career grant support from Medtronic. Dr. Genereux has received speaking fees from Abbott and Cardiovascular Systems. Dr. Valgimigli has received grants from AstraZeneca, Medtronic, and The Medicines Company. Dr. Feres has received speaking fees from Biosensors and Eli Lilly; and has been a consultant for Medtronic and SciTech. Dr. Montalescot has received research grants to the institution or consulting or lecture fees from ADIR, Amgen, AstraZeneca, Bayer, Berlin Chimie, Boehringer Ingelheim, Bristol-Myers Squibb, Beth Israel Deaconess Medical Center, Brigham and Women’s Hospital, The Cardiovascular Research Foundation, Celladon, CME Resources, Daiichi-Sankyo, Eli Lilly, Europa, Elsevier, Fédération Française de Cardiologie, Fondazione Anna Maria Sechi per il Cuore, Gilead, ICAN, Janssen, Lead-Up, Menarini, Medtronic, Merck Sharpe & Dohme, Pfizer, Sanofi, The Medicines Company, The TIMI Study Group, and WebMD. 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. Bhatt is a member of the advisory boards of Cardax, Elsevier Practice Update Cardiology, Medscape Cardiology, and Regado Biosciences; is a member of the boards of directors of the Boston VA Research Institute and the Society of Cardiovascular Patient Care; is chair of the American Heart Association Quality Oversight Committee; is a member of the data monitoring committees of the Duke Clinical Research Institute, the Harvard Clinical Research Institute, the Mayo Clinic, and the Population Health Research Institute; has received honoraria from the American College of Cardiology (senior associate editor, Clinical Trials and News, ACC.org), Belvoir Publications (Editor-in-Chief, Harvard Heart Letter), the Duke Clinical Research Institute (clinical trial steering committees), the Harvard Clinical Research Institute (clinical trial steering committee), HMP Communications (Editor-in-Chief, Journal of Invasive Cardiology), the Journal of the American College of Cardiology (guest editor, associate editor), the Population Health Research Institute (clinical trial steering committee), Slack Publications (chief medical editor, Cardiology Today’s Intervention), the Society of Cardiovascular Patient Care (secretary/treasurer), WebMD (continuing medical education steering committees); has other relationships with Clinical Cardiology (deputy editor), the NCDR-ACTION Registry Steering Committee (vice chair), and the VA CART Research and Publications Committee (chair); has received research funding from Amarin, Amgen, AstraZeneca, Bristol-Myers Squibb, Eisai, Ethicon, Forest Laboratories, Ischemix, Medtronic, Pfizer, Roche, Sanofi, and The Medicines Company; has received royalties from Elsevier (editor, Cardiovascular Intervention: A Companion to Braunwald’s Heart Disease); is a cite co-investigator for Biotronik, Boston Scientific, and St. Jude Medical; is a trustee of the American College of Cardiology; and has conducted unfunded research for FlowCo, PLx Pharma, and Takeda. Dr. Morice has received minor lecture fees from GE, Abbott, and Terumo. All other authors have reported that they have reported that they have no relationships relevant to the contents of this paper to disclose.
- Received October 19, 2016.
- Revision received January 25, 2017.
- Accepted February 10, 2017.
- 2017 American College of Cardiology Foundation