Bleeding-Related Deaths in Relation to the Duration of Dual-Antiplatelet Therapy After Coronary Stenting

Tullio Palmerini, Letizia Bacchi Reggiani, Diego Della Riva, Mattia Romanello, Fausto Feres, Alexandre Abizaid, Martine Gilard, Marie Claude Morice, Marco Valgimigli, Myeong Ki Hong, Byeong Keuk Kim, Yangsoo Jang, Hyo Soo Kim, Kyung Woo Park, Antonio Colombo, Alaide Chieffo, Jung Min Ahn, Seung Jung Park, Stefanie Schüpke, Adnan KastratiGilles Montalescot, Philippe Gabriel Steg, Abdourahmane Diallo, Eric Vicaut, Gerard Helft, Giuseppe Biondi-Zoccai, Bo Xu, Yaling Han, Philippe Genereux, Deepak L. Bhatt, Gregg W. Stone

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)2011-2022
Number of pages12
JournalJournal of the American College of Cardiology
Volume69
Issue number16
DOIs
Publication statusPublished - Apr 25 2017

Keywords

  • drug-eluting stent
  • dual antiplatelet therapy
  • mortality

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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    Palmerini, T., Bacchi Reggiani, L., Della Riva, D., Romanello, M., Feres, F., Abizaid, A., Gilard, M., Morice, M. C., Valgimigli, M., Hong, M. K., Kim, B. K., Jang, Y., Kim, H. S., Park, K. W., Colombo, A., Chieffo, A., Ahn, J. M., Park, S. J., Schüpke, S., ... Stone, G. W. (2017). Bleeding-Related Deaths in Relation to the Duration of Dual-Antiplatelet Therapy After Coronary Stenting. Journal of the American College of Cardiology, 69(16), 2011-2022. https://doi.org/10.1016/j.jacc.2017.02.029