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

T Palmerini, L Bacchi Reggiani, D Della Riva, M Romanello, F Feres, A Abizaid, M Gilard, MC Morice, M Valgimigli, MK Hong, BK Kim, Y Jang, HS Kim, KW Park, A Colombo, A Chieffo, JM Ahn, SJ Park, S Schüpke, A KastratiG Montalescot, PG Steg, A Diallo, E Vicaut, G Helft, G Biondi-Zoccai, B Xu, Y Han, P Genereux, DL Bhatt, GW 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. © 2017 American College of Cardiology Foundation
Original languageEnglish
Pages (from-to)2011-2022
Number of pages12
JournalJournal of the American College of Cardiology
Volume69
Issue number16
DOIs
Publication statusPublished - 2017

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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

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Palmerini, T., Bacchi Reggiani, L., Della Riva, D., Romanello, M., Feres, F., Abizaid, A., ... 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, 69(16), 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, T; Bacchi Reggiani, L; Della Riva, D; Romanello, M; Feres, F; Abizaid, A; Gilard, M; Morice, MC; Valgimigli, M; Hong, MK; 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.

In: Journal of the American College of Cardiology, Vol. 69, No. 16, 2017, p. 2011-2022.

Research output: Contribution to journalArticle

Palmerini, T, Bacchi Reggiani, L, Della Riva, D, Romanello, M, Feres, F, Abizaid, A, Gilard, M, Morice, MC, Valgimigli, M, Hong, MK, 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
Palmerini, T ; Bacchi Reggiani, L ; Della Riva, D ; Romanello, M ; Feres, F ; Abizaid, A ; Gilard, M ; Morice, MC ; Valgimigli, M ; Hong, MK ; 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. / 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. {\circledC} 2017 American College of Cardiology Foundation",
author = "T Palmerini and {Bacchi Reggiani}, L and {Della Riva}, D and M Romanello and F Feres and A Abizaid and M Gilard and MC Morice and M Valgimigli and MK Hong and BK Kim and Y Jang and HS Kim and KW Park and A Colombo and A Chieffo and JM Ahn and SJ Park and S Sch{\"u}pke and A Kastrati and G Montalescot and PG Steg and A Diallo and E Vicaut and G Helft and G Biondi-Zoccai and B Xu and Y Han and P Genereux and DL Bhatt and GW Stone",
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TY - JOUR

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

AU - Palmerini, T

AU - Bacchi Reggiani, L

AU - Della Riva, D

AU - Romanello, M

AU - Feres, F

AU - Abizaid, A

AU - Gilard, M

AU - Morice, MC

AU - Valgimigli, M

AU - Hong, MK

AU - Kim, BK

AU - Jang, Y

AU - Kim, HS

AU - Park, KW

AU - Colombo, A

AU - Chieffo, A

AU - Ahn, JM

AU - Park, SJ

AU - Schüpke, S

AU - Kastrati, A

AU - Montalescot, G

AU - Steg, PG

AU - Diallo, A

AU - Vicaut, E

AU - Helft, G

AU - Biondi-Zoccai, G

AU - Xu, B

AU - Han, Y

AU - Genereux, P

AU - Bhatt, DL

AU - Stone, GW

PY - 2017

Y1 - 2017

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. © 2017 American College of Cardiology Foundation

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. © 2017 American College of Cardiology Foundation

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 -