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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
  
  
  BACKGROUND
  None.
authors.affiliation: Dipartimento Cardio-Toraco-Vascolare, University of Bologna, Italy.
authors.forename: Tullio
authors.initials: T
authors.lastname: Palmerini
authors.affiliation: Oxford Heart Center, Oxford University, Oxford, UK.
authors.forename: Umberto
authors.initials: U
authors.lastname: Benedetto
authors.affiliation: Dipartimento Cardio-Toraco-Vascolare, University of Bologna, Italy.
authors.forename: Letizia
authors.initials: L
authors.lastname: Bacchi-Reggiani
authors.affiliation: Dipartimento Cardio-Toraco-Vascolare, University of Bologna, Italy.
authors.forename: Diego
authors.initials: D
authors.lastname: Della Riva
authors.affiliation: Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Latina, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Biondi-Zoccai
authors.affiliation: Istituto Dante Pazzanese de Cardiologia, Sao Paulo, Brazil.
authors.forename: Fausto
authors.initials: F
authors.lastname: Feres
authors.affiliation: Istituto Dante Pazzanese de Cardiologia, Sao Paulo, Brazil.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Abizaid
authors.affiliation: Severance Cardiovascular Hospital and Science Institute, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Myeong-Ki
authors.initials: MK
authors.lastname: Hong
authors.affiliation: Severance Cardiovascular Hospital and Science Institute, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Byeong-Keuk
authors.initials: BK
authors.lastname: Kim
authors.affiliation: Severance Cardiovascular Hospital and Science Institute, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Yangsoo
authors.initials: Y
authors.lastname: Jang
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.
authors.forename: Hyo-Soo
authors.initials: HS
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.
authors.forename: Kyung Woo
authors.initials: KW
authors.lastname: Park
authors.affiliation: Columbia University Medical Center/New York-Presbyterian Hospital and the Cardiovascular Research Foundation, New York, NY, USA; Hôpital du Sacré-Coeur de Montréal, Montréal, Québec, Canada.
authors.forename: Philippe
authors.initials: P
authors.lastname: Genereux
authors.affiliation: Brigham and Women's Hospital Heart and Vascular Center and Harvard Medical School, Boston, MA, USA.
authors.forename: Deepak L
authors.initials: DL
authors.lastname: Bhatt
authors.affiliation: Dipartimento Cardio-Toraco-Vascolare, University of Bologna, Italy.
authors.forename: Carlotta
authors.initials: C
authors.lastname: Orlandi
authors.affiliation: Policlinico S Matteo, Pavia, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: De Servi
authors.affiliation: Oxford Heart Center, Oxford University, Oxford, UK.
authors.forename: Mario
authors.initials: M
authors.lastname: Petrou
authors.affiliation: Dipartimento Cardio-Toraco-Vascolare, University of Bologna, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Rapezzi
authors.affiliation: Columbia University Medical Center/New York-Presbyterian Hospital and the Cardiovascular Research Foundation, New York, NY, USA. Electronic address: gs2184@columbia.edu.
authors.forename: Gregg W
authors.initials: GW
authors.lastname: Stone
mesh_terms: D003324:Coronary Artery Disease / Q000401:mortality* / Q000628:therapy*; D004359:Drug Therapy, Combination; D054855:Drug-Eluting Stents; D006470:Hemorrhage / Q000453:epidemiology; D006801:Humans; D009203:Myocardial Infarction / Q000453:epidemiology / Q000517:prevention & control; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects*; D016032:Randomized Controlled Trials as Topic; D013927:Thrombosis / Q000453:epidemiology / Q000517:prevention & control; D013997:Time Factors
chemical_list: D010975:Platelet Aggregation Inhibitors