Tullio Palmerini1, Letizia Bacchi Reggiani1, Diego Della Riva1, Mattia Romanello1, Fausto Feres2, Alexandre Abizaid2, Martine Gilard3, Marie-Claude Morice4, Marco Valgimigli5, Myeong-Ki Hong6, Byeong-Keuk Kim6, Yangsoo Jang6, Hyo-Soo Kim7, Kyung Woo Park7, Antonio Colombo8, Alaide Chieffo8, Jung-Min Ahn9, Seung-Jung Park9, Stefanie Schüpke10, Adnan Kastrati10, Gilles Montalescot11, Philippe Gabriel Steg12, Abdourahmane Diallo13, Eric Vicaut13, Gerard Helft14, Giuseppe Biondi-Zoccai15, Bo Xu16, Yaling Han17, Philippe Genereux18, Deepak L Bhatt19, Gregg W Stone20. 1. Dipartimento Cardio-Toraco-Vascolare, University of Bologna, Bologna, Italy. 2. Istituto Dante Pazzanese de Cardiologia, São Paulo, Brazil. 3. Department of Cardiology, Brest University, Brest, France. 4. Générale de Santé, Institut Cardiovasculaire Paris Sud, Massy, France. 5. Swiss Cardiovascular Center, Bern, Switzerland. 6. Severance Cardiovascular Hospital, Yonsei University College of Medicine, Seoul, South Korea. 7. Department of Internal Medicine, Seoul National University Hospital, Seoul, South Korea. 8. San Raffaele Scientific Institute, Milan, Italy. 9. The Heart Institute, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea. 10. ISAResearch Center, Deutsches Herzzentrum and Deutsches Zentrum für Herz-Kreislauf-Forschung, partner site Munich Heart Alliance, Munich, Germany. 11. Sorbonne Université-Paris 6, ACTION Study Group, Institut de Cardiologie, Centre Hospitalier Universitaire Pitié-Salpêtrière, Paris, France. 12. Hôpital Bichat, Assistance Publique-Hôpitaux de Paris, Paris, France. 13. Unité de Recherche Clinique Lariboisière Saint-Louis Hôpital Fernand Widal, Assistance Publique-Hôpitaux de Paris, Paris, France. 14. Institut de Cardiologie, Hôpital Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, Paris, France. 15. Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Latina, and Department of AngioCardioNeurology, IRCCS Neuromed, Pozzilli, Italy. 16. Catheterization Laboratory, Fu Wai Hospital, National Center for Cardiovascular Diseases, Beijing, China. 17. Department of Cardiology, General Hospital of Shenyang Military Region, Shenyang, China. 18. Columbia University Medical Center/New York-Presbyterian Hospital and the Cardiovascular Research Foundation, New York, New York. 19. Brigham and Women's Hospital Heart and Vascular Center and Harvard Medical School, Boston, Massachusetts. 20. Columbia University Medical Center/New York-Presbyterian Hospital and the Cardiovascular Research Foundation, New York, New York. Electronic address: gs2184@columbia.edu.
Abstract
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.
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.
Authors: Thomas A Mavrakanas; Yiannis S Chatzizisis; Karim Gariani; Dean J Kereiakes; Giuseppe Gargiulo; Gérard Helft; Martine Gilard; Fausto Feres; Ricardo A Costa; Marie-Claude Morice; Jean-Louis Georges; Marco Valgimigli; Deepak L Bhatt; Laura Mauri; David M Charytan Journal: Clin J Am Soc Nephrol Date: 2019-04-22 Impact factor: 8.237
Authors: M Verdoia; H Suryapranata; S Damen; C Camaro; E Benit; L Barbieri; S Rasoul; H B Liew; J Polad; W A W Ahmad; R Zambahari; J Lalmand; R J van der Schaaf; T H Koh; P Timmermans; D Dilling-Boer; L F Veenstra; A W J Van't Hof; S W L Lee; V Roolvink; E Ligtenberg; S Postma; E J J Kolkman; M A Brouwer; E Kedhi; G De Luca Journal: J Thromb Thrombolysis Date: 2021-04-13 Impact factor: 2.300
Authors: J M Ten Berg; B Zwart; A W J van 't Hof; A Liem; J Waltenberger; R J de Winter; J W Jukema Journal: Neth Heart J Date: 2017-12 Impact factor: 2.380