Mortality in patients treated with extended duration dual antiplatelet therapy after drug-eluting stent implantation

A pairwise and Bayesian network meta-analysis of randomised trials

Tullio Palmerini, Umberto Benedetto, Letizia Bacchi-Reggiani, Diego Della Riva, Giuseppe Biondi-Zoccai, Fausto Feres, Alexandre Abizaid, Myeong Ki Hong, Byeong Keuk Kim, Yangsoo Jang, Hyo Soo Kim, Kyung Woo Park, Philippe Genereux, Deepak L. Bhatt, Carlotta Orlandi, Stefano De Servi, Mario Petrou, Claudio Rapezzi, Gregg W. Stone

Research output: Contribution to journalArticle

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Abstract

Background Despite recent studies, the optimum duration of dual antiplatelet therapy (DAPT) after coronary drug-eluting stent placement remains uncertain. We performed a meta-analysis with several analytical approaches to investigate mortality and other clinical outcomes with different DAPT strategies. Methods We searched Medline, Embase, Cochrane databases, and proceedings of international meetings on Nov 20, 2014, for randomised controlled trials comparing different DAPT durations after drug-eluting stent implantation. We extracted study design, inclusion and exclusion criteria, sample characteristics, and clinical outcomes. DAPT duration was categorised in each study as shorter versus longer, and as 6 months or shorter versus 1 year versus longer than 1 year. Analyses were done by both frequentist and Bayesian approaches. Findings We identified ten trials published between Dec 16, 2011, and Nov 16, 2014, including 31 666 randomly assigned patients. By frequentist pairwise meta-analysis, shorter DAPT was associated with significantly lower all-cause mortality compared with longer DAPT (HR 0·82, 95% CI 0·69-0·98; p=0·02; number needed to treat [NNT]=325), with no significant heterogeneity apparent across trials. The reduced mortality with shorter compared with longer DAPT was attributable to lower non-cardiac mortality (0·67, 0·51-0·89; p=0·006; NNT=347), with similar cardiac mortality (0·93, 0·73-1·17; p=0.52). Shorter DAPT was also associated with a lower risk of major bleeding, but a higher risk of myocardial infarction and stent thrombosis. We noted similar results in a Bayesian framework with non-informative priors. By network meta-analysis, patients treated with 6-month or shorter DAPT and 1-year DAPT had higher risk of myocardial infarction and stent thrombosis but lower risk of mortality compared with patients treated with DAPT for longer than 1 year. Patients treated with DAPT for 6 months or shorter had similar rates of mortality, myocardial infarction, and stent thrombosis, but lower rates of major bleeding than did patients treated with 1-year DAPT. Interpretation Although treatment with DAPT beyond 1 year after drug-eluting stent implantation reduces myocardial infarction and stent thrombosis, it is associated with increased mortality because of an increased risk of non-cardiovascular mortality not offset by a reduction in cardiac mortality. Funding None.

Original languageEnglish (US)
Pages (from-to)2371-2382
Number of pages12
JournalThe Lancet
Volume385
Issue number9985
DOIs
StatePublished - Jun 13 2015

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Drug-Eluting Stents
Mortality
Therapeutics
Stents
Thrombosis
Myocardial Infarction
Numbers Needed To Treat
Network Meta-Analysis
Meta-Analysis
Hemorrhage
Bayes Theorem

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this

Palmerini, Tullio ; Benedetto, Umberto ; Bacchi-Reggiani, Letizia ; Riva, Diego Della ; Biondi-Zoccai, Giuseppe ; Feres, Fausto ; Abizaid, Alexandre ; Hong, Myeong Ki ; Kim, Byeong Keuk ; Jang, Yangsoo ; Kim, Hyo Soo ; Park, Kyung Woo ; Genereux, Philippe ; Bhatt, Deepak L. ; Orlandi, Carlotta ; De Servi, Stefano ; Petrou, Mario ; Rapezzi, Claudio ; Stone, Gregg W. / Mortality in patients treated with extended duration dual antiplatelet therapy after drug-eluting stent implantation : A pairwise and Bayesian network meta-analysis of randomised trials. In: The Lancet. 2015 ; Vol. 385, No. 9985. pp. 2371-2382.
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abstract = "Background Despite recent studies, the optimum duration of dual antiplatelet therapy (DAPT) after coronary drug-eluting stent placement remains uncertain. We performed a meta-analysis with several analytical approaches to investigate mortality and other clinical outcomes with different DAPT strategies. Methods We searched Medline, Embase, Cochrane databases, and proceedings of international meetings on Nov 20, 2014, for randomised controlled trials comparing different DAPT durations after drug-eluting stent implantation. We extracted study design, inclusion and exclusion criteria, sample characteristics, and clinical outcomes. DAPT duration was categorised in each study as shorter versus longer, and as 6 months or shorter versus 1 year versus longer than 1 year. Analyses were done by both frequentist and Bayesian approaches. Findings We identified ten trials published between Dec 16, 2011, and Nov 16, 2014, including 31 666 randomly assigned patients. By frequentist pairwise meta-analysis, shorter DAPT was associated with significantly lower all-cause mortality compared with longer DAPT (HR 0·82, 95{\%} CI 0·69-0·98; p=0·02; number needed to treat [NNT]=325), with no significant heterogeneity apparent across trials. The reduced mortality with shorter compared with longer DAPT was attributable to lower non-cardiac mortality (0·67, 0·51-0·89; p=0·006; NNT=347), with similar cardiac mortality (0·93, 0·73-1·17; p=0.52). Shorter DAPT was also associated with a lower risk of major bleeding, but a higher risk of myocardial infarction and stent thrombosis. We noted similar results in a Bayesian framework with non-informative priors. By network meta-analysis, patients treated with 6-month or shorter DAPT and 1-year DAPT had higher risk of myocardial infarction and stent thrombosis but lower risk of mortality compared with patients treated with DAPT for longer than 1 year. Patients treated with DAPT for 6 months or shorter had similar rates of mortality, myocardial infarction, and stent thrombosis, but lower rates of major bleeding than did patients treated with 1-year DAPT. Interpretation Although treatment with DAPT beyond 1 year after drug-eluting stent implantation reduces myocardial infarction and stent thrombosis, it is associated with increased mortality because of an increased risk of non-cardiovascular mortality not offset by a reduction in cardiac mortality. Funding None.",
author = "Tullio Palmerini and Umberto Benedetto and Letizia Bacchi-Reggiani and Riva, {Diego Della} and Giuseppe Biondi-Zoccai and Fausto Feres and Alexandre Abizaid and Hong, {Myeong Ki} and Kim, {Byeong Keuk} and Yangsoo Jang and Kim, {Hyo Soo} and Park, {Kyung Woo} and Philippe Genereux and Bhatt, {Deepak L.} and Carlotta Orlandi and {De Servi}, Stefano and Mario Petrou and Claudio Rapezzi and Stone, {Gregg W.}",
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Palmerini, T, Benedetto, U, Bacchi-Reggiani, L, Riva, DD, Biondi-Zoccai, G, Feres, F, Abizaid, A, Hong, MK, Kim, BK, Jang, Y, Kim, HS, Park, KW, Genereux, P, Bhatt, DL, Orlandi, C, De Servi, S, Petrou, M, Rapezzi, C & Stone, GW 2015, 'Mortality in patients treated with extended duration dual antiplatelet therapy after drug-eluting stent implantation: A pairwise and Bayesian network meta-analysis of randomised trials', The Lancet, vol. 385, no. 9985, pp. 2371-2382. https://doi.org/10.1016/S0140-6736(15)60263-X

Mortality in patients treated with extended duration dual antiplatelet therapy after drug-eluting stent implantation : A pairwise and Bayesian network meta-analysis of randomised trials. / Palmerini, Tullio; Benedetto, Umberto; Bacchi-Reggiani, Letizia; Riva, Diego Della; Biondi-Zoccai, Giuseppe; Feres, Fausto; Abizaid, Alexandre; Hong, Myeong Ki; Kim, Byeong Keuk; Jang, Yangsoo; Kim, Hyo Soo; Park, Kyung Woo; Genereux, Philippe; Bhatt, Deepak L.; Orlandi, Carlotta; De Servi, Stefano; Petrou, Mario; Rapezzi, Claudio; Stone, Gregg W.

In: The Lancet, Vol. 385, No. 9985, 13.06.2015, p. 2371-2382.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Mortality in patients treated with extended duration dual antiplatelet therapy after drug-eluting stent implantation

T2 - A pairwise and Bayesian network meta-analysis of randomised trials

AU - Palmerini, Tullio

AU - Benedetto, Umberto

AU - Bacchi-Reggiani, Letizia

AU - Riva, Diego Della

AU - Biondi-Zoccai, Giuseppe

AU - Feres, Fausto

AU - Abizaid, Alexandre

AU - Hong, Myeong Ki

AU - Kim, Byeong Keuk

AU - Jang, Yangsoo

AU - Kim, Hyo Soo

AU - Park, Kyung Woo

AU - Genereux, Philippe

AU - Bhatt, Deepak L.

AU - Orlandi, Carlotta

AU - De Servi, Stefano

AU - Petrou, Mario

AU - Rapezzi, Claudio

AU - Stone, Gregg W.

PY - 2015/6/13

Y1 - 2015/6/13

N2 - Background Despite recent studies, the optimum duration of dual antiplatelet therapy (DAPT) after coronary drug-eluting stent placement remains uncertain. We performed a meta-analysis with several analytical approaches to investigate mortality and other clinical outcomes with different DAPT strategies. Methods We searched Medline, Embase, Cochrane databases, and proceedings of international meetings on Nov 20, 2014, for randomised controlled trials comparing different DAPT durations after drug-eluting stent implantation. We extracted study design, inclusion and exclusion criteria, sample characteristics, and clinical outcomes. DAPT duration was categorised in each study as shorter versus longer, and as 6 months or shorter versus 1 year versus longer than 1 year. Analyses were done by both frequentist and Bayesian approaches. Findings We identified ten trials published between Dec 16, 2011, and Nov 16, 2014, including 31 666 randomly assigned patients. By frequentist pairwise meta-analysis, shorter DAPT was associated with significantly lower all-cause mortality compared with longer DAPT (HR 0·82, 95% CI 0·69-0·98; p=0·02; number needed to treat [NNT]=325), with no significant heterogeneity apparent across trials. The reduced mortality with shorter compared with longer DAPT was attributable to lower non-cardiac mortality (0·67, 0·51-0·89; p=0·006; NNT=347), with similar cardiac mortality (0·93, 0·73-1·17; p=0.52). Shorter DAPT was also associated with a lower risk of major bleeding, but a higher risk of myocardial infarction and stent thrombosis. We noted similar results in a Bayesian framework with non-informative priors. By network meta-analysis, patients treated with 6-month or shorter DAPT and 1-year DAPT had higher risk of myocardial infarction and stent thrombosis but lower risk of mortality compared with patients treated with DAPT for longer than 1 year. Patients treated with DAPT for 6 months or shorter had similar rates of mortality, myocardial infarction, and stent thrombosis, but lower rates of major bleeding than did patients treated with 1-year DAPT. Interpretation Although treatment with DAPT beyond 1 year after drug-eluting stent implantation reduces myocardial infarction and stent thrombosis, it is associated with increased mortality because of an increased risk of non-cardiovascular mortality not offset by a reduction in cardiac mortality. Funding None.

AB - Background Despite recent studies, the optimum duration of dual antiplatelet therapy (DAPT) after coronary drug-eluting stent placement remains uncertain. We performed a meta-analysis with several analytical approaches to investigate mortality and other clinical outcomes with different DAPT strategies. Methods We searched Medline, Embase, Cochrane databases, and proceedings of international meetings on Nov 20, 2014, for randomised controlled trials comparing different DAPT durations after drug-eluting stent implantation. We extracted study design, inclusion and exclusion criteria, sample characteristics, and clinical outcomes. DAPT duration was categorised in each study as shorter versus longer, and as 6 months or shorter versus 1 year versus longer than 1 year. Analyses were done by both frequentist and Bayesian approaches. Findings We identified ten trials published between Dec 16, 2011, and Nov 16, 2014, including 31 666 randomly assigned patients. By frequentist pairwise meta-analysis, shorter DAPT was associated with significantly lower all-cause mortality compared with longer DAPT (HR 0·82, 95% CI 0·69-0·98; p=0·02; number needed to treat [NNT]=325), with no significant heterogeneity apparent across trials. The reduced mortality with shorter compared with longer DAPT was attributable to lower non-cardiac mortality (0·67, 0·51-0·89; p=0·006; NNT=347), with similar cardiac mortality (0·93, 0·73-1·17; p=0.52). Shorter DAPT was also associated with a lower risk of major bleeding, but a higher risk of myocardial infarction and stent thrombosis. We noted similar results in a Bayesian framework with non-informative priors. By network meta-analysis, patients treated with 6-month or shorter DAPT and 1-year DAPT had higher risk of myocardial infarction and stent thrombosis but lower risk of mortality compared with patients treated with DAPT for longer than 1 year. Patients treated with DAPT for 6 months or shorter had similar rates of mortality, myocardial infarction, and stent thrombosis, but lower rates of major bleeding than did patients treated with 1-year DAPT. Interpretation Although treatment with DAPT beyond 1 year after drug-eluting stent implantation reduces myocardial infarction and stent thrombosis, it is associated with increased mortality because of an increased risk of non-cardiovascular mortality not offset by a reduction in cardiac mortality. Funding None.

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DO - 10.1016/S0140-6736(15)60263-X

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JO - The Lancet

JF - The Lancet

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