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, Myeongki 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 Kastrati & 11 others Gilles 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

35 Citations (Scopus)

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 - 2017 Apr 25

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Hemorrhage
Randomized Controlled Trials
Mortality
Therapeutics
Drug-Eluting Stents
Confidence Intervals
Meta-Analysis
Intention to Treat Analysis
MEDLINE
Population
Cause of Death
Multivariate Analysis
Databases

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

Cite this

Palmerini, T., Bacchi Reggiani, L., Della Riva, D., Romanello, M., Feres, F., Abizaid, A., ... 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
Palmerini, Tullio ; Bacchi Reggiani, Letizia ; Della Riva, Diego ; Romanello, Mattia ; Feres, Fausto ; Abizaid, Alexandre ; Gilard, Martine ; Morice, Marie Claude ; Valgimigli, Marco ; Hong, Myeongki ; Kim, Byeong Keuk ; Jang, Yangsoo ; Kim, Hyo Soo ; Park, Kyung Woo ; Colombo, Antonio ; Chieffo, Alaide ; Ahn, Jung Min ; Park, Seung Jung ; Schüpke, Stefanie ; Kastrati, Adnan ; Montalescot, Gilles ; Steg, Philippe Gabriel ; Diallo, Abdourahmane ; Vicaut, Eric ; Helft, Gerard ; Biondi-Zoccai, Giuseppe ; Xu, Bo ; Han, Yaling ; Genereux, Philippe ; Bhatt, Deepak L. ; Stone, Gregg W. / Bleeding-Related Deaths in Relation to the Duration of Dual-Antiplatelet Therapy After Coronary Stenting. In: Journal of the American College of Cardiology. 2017 ; Vol. 69, No. 16. pp. 2011-2022.
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title = "Bleeding-Related Deaths in Relation to the Duration of Dual-Antiplatelet Therapy After Coronary Stenting",
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.",
author = "Tullio Palmerini and {Bacchi Reggiani}, Letizia and {Della Riva}, Diego and Mattia Romanello and Fausto Feres and Alexandre Abizaid and Martine Gilard and Morice, {Marie Claude} and Marco Valgimigli and Myeongki Hong and Kim, {Byeong Keuk} and Yangsoo Jang and Kim, {Hyo Soo} and Park, {Kyung Woo} and Antonio Colombo and Alaide Chieffo and Ahn, {Jung Min} and Park, {Seung Jung} and Stefanie Sch{\"u}pke and Adnan Kastrati and Gilles Montalescot and Steg, {Philippe Gabriel} and Abdourahmane Diallo and Eric Vicaut and Gerard Helft and Giuseppe Biondi-Zoccai and Bo Xu and Yaling Han and Philippe Genereux and Bhatt, {Deepak L.} and Stone, {Gregg W.}",
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language = "English",
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pages = "2011--2022",
journal = "Journal of the American College of Cardiology",
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Palmerini, T, Bacchi Reggiani, L, Della Riva, D, Romanello, M, Feres, F, Abizaid, A, Gilard, M, Morice, MC, Valgimigli, M, Hong, M, Kim, BK, Jang, Y, Kim, HS, Park, KW, Colombo, A, Chieffo, A, Ahn, JM, Park, SJ, Schüpke, S, Kastrati, A, Montalescot, G, Steg, PG, Diallo, A, Vicaut, E, Helft, G, Biondi-Zoccai, G, Xu, B, Han, Y, Genereux, P, Bhatt, DL & Stone, GW 2017, 'Bleeding-Related Deaths in Relation to the Duration of Dual-Antiplatelet Therapy After Coronary Stenting', Journal of the American College of Cardiology, vol. 69, no. 16, pp. 2011-2022. https://doi.org/10.1016/j.jacc.2017.02.029

Bleeding-Related Deaths in Relation to the Duration of Dual-Antiplatelet Therapy After Coronary Stenting. / Palmerini, Tullio; Bacchi Reggiani, Letizia; Della Riva, Diego; Romanello, Mattia; Feres, Fausto; Abizaid, Alexandre; Gilard, Martine; Morice, Marie Claude; Valgimigli, Marco; Hong, Myeongki; Kim, Byeong Keuk; Jang, Yangsoo; Kim, Hyo Soo; Park, Kyung Woo; Colombo, Antonio; Chieffo, Alaide; Ahn, Jung Min; Park, Seung Jung; Schüpke, Stefanie; Kastrati, Adnan; Montalescot, Gilles; Steg, Philippe Gabriel; Diallo, Abdourahmane; Vicaut, Eric; Helft, Gerard; Biondi-Zoccai, Giuseppe; Xu, Bo; Han, Yaling; Genereux, Philippe; Bhatt, Deepak L.; Stone, Gregg W.

In: Journal of the American College of Cardiology, Vol. 69, No. 16, 25.04.2017, p. 2011-2022.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Bleeding-Related Deaths in Relation to the Duration of Dual-Antiplatelet Therapy After Coronary Stenting

AU - Palmerini, Tullio

AU - Bacchi Reggiani, Letizia

AU - Della Riva, Diego

AU - Romanello, Mattia

AU - Feres, Fausto

AU - Abizaid, Alexandre

AU - Gilard, Martine

AU - Morice, Marie Claude

AU - Valgimigli, Marco

AU - Hong, Myeongki

AU - Kim, Byeong Keuk

AU - Jang, Yangsoo

AU - Kim, Hyo Soo

AU - Park, Kyung Woo

AU - Colombo, Antonio

AU - Chieffo, Alaide

AU - Ahn, Jung Min

AU - Park, Seung Jung

AU - Schüpke, Stefanie

AU - Kastrati, Adnan

AU - Montalescot, Gilles

AU - Steg, Philippe Gabriel

AU - Diallo, Abdourahmane

AU - Vicaut, Eric

AU - Helft, Gerard

AU - Biondi-Zoccai, Giuseppe

AU - Xu, Bo

AU - Han, Yaling

AU - Genereux, Philippe

AU - Bhatt, Deepak L.

AU - Stone, Gregg W.

PY - 2017/4/25

Y1 - 2017/4/25

N2 - 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.

AB - 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.

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U2 - 10.1016/j.jacc.2017.02.029

DO - 10.1016/j.jacc.2017.02.029

M3 - Article

VL - 69

SP - 2011

EP - 2022

JO - Journal of the American College of Cardiology

JF - Journal of the American College of Cardiology

SN - 0735-1097

IS - 16

ER -