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

doi: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

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

Department of Internal Medicine

Research output: Contribution to journal › Article › peer-review

335 Citations (Scopus)

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 language	English
Pages (from-to)	2371-2382
Number of pages	12
Journal	The Lancet
Volume	385
Issue number	9985
DOIs	https://doi.org/10.1016/S0140-6736(15)60263-X
Publication status	Published - 2015 Jun 13

Bibliographical note

Funding Information:
None of the funders of any of the individual trials had any role in the study design, data collection, data interpretation or drafting or review of the manuscript. TP has received speaker fee from Abbott Vascular and research grant from Eli Lilly. GB-Z has consulted for Bayer Pharma, and Novartis, has lectured for Abbott Vascular, AstraZeneca, DirectFlow Medical, and St Jude Medical, and has received career grant support from Medtronic. PG has received speaker fees from Abbott and Cardiovascular System Inc. FF has received speaker fees from Biosensors and Eli Lilly, and has been consultant for Medtronic and Scitech. DLB discloses the following relationships: advisory board of Cardax, Elsevier Practice Update Cardiology, Medscape Cardiology, Regado Biosciences; Board of Directors of Boston VA Research Institute, Society of Cardiovascular Patient Care; Chair of American Heart Association Get With The Guidelines Steering Committee; Data Monitoring Committees of Duke Clinical Research Institute, Harvard Clinical Research Institute, Mayo Clinic, and Population Health Research Institute; Honoraria from American College of Cardiology (Senior Associate Editor, Clinical Trials and News, ACC.org ), Belvoir Publications (Editor in Chief, Harvard Heart Letter), Duke Clinical Research Institute (clinical trial steering committees), Harvard Clinical Research Institute (clinical trial steering committee), HMP Communications (Editor in Chief, Journal of Invasive Cardiology), Journal of the American College of Cardiology (Associate Editor; Section Editor, Pharmacology), Population Health Research Institute (clinical trial steering committee), Slack Publications (Chief Medical Editor, Cardiology Today's Intervention), WebMD (CME steering committees); and Clinical Cardiology (Deputy Editor); research funding from Amarin, AstraZeneca, Bristol-Myers Squibb, Eisai, Ethicon, Forest Laboratories, Ischemix, Medtronic, Pfizer, Roche, Sanofi-Aventis, and The Medicines Company; and unfunded research from FlowCo, PLx Pharma, Takeda. GWS has served as a consultant for Osprey, Reva, Boston Scientific, AstraZeneca, Eli Lilly, Daiichi Sankyo partnership, Gilead, InspireMD, TherOx, Atrium, Volcano, InfraReDx, Miracor, Velomedix, CSI, AGA, and Thoratec, and has equity in the Biostar family of funds, the MedFocus family of funds, Caliber, Guided Delivery Systems, Micardia, Embrella, and VNT. The other authors declare no competing interests.

Publisher Copyright:
© 2015 Elsevier Ltd.

All Science Journal Classification (ASJC) codes

Medicine(all)

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10.1016/S0140-6736(15)60263-X

Cite this

Palmerini, T., Benedetto, U., Bacchi-Reggiani, L., Riva, D. D., Biondi-Zoccai, G., Feres, F., Abizaid, A., Hong, M. K., Kim, B. K., Jang, Y., Kim, H. S., Park, K. W., Genereux, P., Bhatt, D. L., Orlandi, C., De Servi, S., Petrou, M., Rapezzi, C., & Stone, G. W. (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, 385(9985), 2371-2382. https://doi.org/10.1016/S0140-6736(15)60263-X

@article{1482e23ce25f4b3391cffc32b7cd639c,

title = "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",

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.}",

note = "Funding Information: None of the funders of any of the individual trials had any role in the study design, data collection, data interpretation or drafting or review of the manuscript. TP has received speaker fee from Abbott Vascular and research grant from Eli Lilly. GB-Z has consulted for Bayer Pharma, and Novartis, has lectured for Abbott Vascular, AstraZeneca, DirectFlow Medical, and St Jude Medical, and has received career grant support from Medtronic. PG has received speaker fees from Abbott and Cardiovascular System Inc. FF has received speaker fees from Biosensors and Eli Lilly, and has been consultant for Medtronic and Scitech. DLB discloses the following relationships: advisory board of Cardax, Elsevier Practice Update Cardiology, Medscape Cardiology, Regado Biosciences; Board of Directors of Boston VA Research Institute, Society of Cardiovascular Patient Care; Chair of American Heart Association Get With The Guidelines Steering Committee; Data Monitoring Committees of Duke Clinical Research Institute, Harvard Clinical Research Institute, Mayo Clinic, and Population Health Research Institute; Honoraria from American College of Cardiology (Senior Associate Editor, Clinical Trials and News, ACC.org ), Belvoir Publications (Editor in Chief, Harvard Heart Letter), Duke Clinical Research Institute (clinical trial steering committees), Harvard Clinical Research Institute (clinical trial steering committee), HMP Communications (Editor in Chief, Journal of Invasive Cardiology), Journal of the American College of Cardiology (Associate Editor; Section Editor, Pharmacology), Population Health Research Institute (clinical trial steering committee), Slack Publications (Chief Medical Editor, Cardiology Today's Intervention), WebMD (CME steering committees); and Clinical Cardiology (Deputy Editor); research funding from Amarin, AstraZeneca, Bristol-Myers Squibb, Eisai, Ethicon, Forest Laboratories, Ischemix, Medtronic, Pfizer, Roche, Sanofi-Aventis, and The Medicines Company; and unfunded research from FlowCo, PLx Pharma, Takeda. GWS has served as a consultant for Osprey, Reva, Boston Scientific, AstraZeneca, Eli Lilly, Daiichi Sankyo partnership, Gilead, InspireMD, TherOx, Atrium, Volcano, InfraReDx, Miracor, Velomedix, CSI, AGA, and Thoratec, and has equity in the Biostar family of funds, the MedFocus family of funds, Caliber, Guided Delivery Systems, Micardia, Embrella, and VNT. The other authors declare no competing interests. Publisher Copyright: {\textcopyright} 2015 Elsevier Ltd.",

year = "2015",

month = jun,

day = "13",

doi = "10.1016/S0140-6736(15)60263-X",

language = "English",

volume = "385",

pages = "2371--2382",

journal = "The Lancet",

issn = "0140-6736",

publisher = "Elsevier Limited",

number = "9985",

}

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

Research output: Contribution to journal › Article › peer-review

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.

N1 - Funding Information: None of the funders of any of the individual trials had any role in the study design, data collection, data interpretation or drafting or review of the manuscript. TP has received speaker fee from Abbott Vascular and research grant from Eli Lilly. GB-Z has consulted for Bayer Pharma, and Novartis, has lectured for Abbott Vascular, AstraZeneca, DirectFlow Medical, and St Jude Medical, and has received career grant support from Medtronic. PG has received speaker fees from Abbott and Cardiovascular System Inc. FF has received speaker fees from Biosensors and Eli Lilly, and has been consultant for Medtronic and Scitech. DLB discloses the following relationships: advisory board of Cardax, Elsevier Practice Update Cardiology, Medscape Cardiology, Regado Biosciences; Board of Directors of Boston VA Research Institute, Society of Cardiovascular Patient Care; Chair of American Heart Association Get With The Guidelines Steering Committee; Data Monitoring Committees of Duke Clinical Research Institute, Harvard Clinical Research Institute, Mayo Clinic, and Population Health Research Institute; Honoraria from American College of Cardiology (Senior Associate Editor, Clinical Trials and News, ACC.org ), Belvoir Publications (Editor in Chief, Harvard Heart Letter), Duke Clinical Research Institute (clinical trial steering committees), Harvard Clinical Research Institute (clinical trial steering committee), HMP Communications (Editor in Chief, Journal of Invasive Cardiology), Journal of the American College of Cardiology (Associate Editor; Section Editor, Pharmacology), Population Health Research Institute (clinical trial steering committee), Slack Publications (Chief Medical Editor, Cardiology Today's Intervention), WebMD (CME steering committees); and Clinical Cardiology (Deputy Editor); research funding from Amarin, AstraZeneca, Bristol-Myers Squibb, Eisai, Ethicon, Forest Laboratories, Ischemix, Medtronic, Pfizer, Roche, Sanofi-Aventis, and The Medicines Company; and unfunded research from FlowCo, PLx Pharma, Takeda. GWS has served as a consultant for Osprey, Reva, Boston Scientific, AstraZeneca, Eli Lilly, Daiichi Sankyo partnership, Gilead, InspireMD, TherOx, Atrium, Volcano, InfraReDx, Miracor, Velomedix, CSI, AGA, and Thoratec, and has equity in the Biostar family of funds, the MedFocus family of funds, Caliber, Guided Delivery Systems, Micardia, Embrella, and VNT. The other authors declare no competing interests. Publisher Copyright: © 2015 Elsevier Ltd.

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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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

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