title: Duration of Triple Therapy in Patients Requiring Oral Anticoagulation After Drug-Eluting Stent Implantation: The ISAR-TRIPLE Trial.
abstract: BACKGROUND
  Patients receiving oral anticoagulation (OAC) who undergo drug-eluting stent (DES) implantation require additional dual antiplatelet therapy with aspirin and clopidogrel. Such triple therapy confers an elevated bleeding risk, and its optimal duration is not known.
  
  
  OBJECTIVE
  The goal of this study was to evaluate whether shortening the duration of clopidogrel therapy from 6 months to 6 weeks after DES implantation was associated with a superior net clinical outcome in patients receiving concomitant aspirin and OAC.
  
  
  METHODS
  In this randomized, open-label trial, we enrolled patients receiving OAC who underwent DES implantation at 3 European centers between September 2008 and December 2013. A total of 614 patients receiving concomitant aspirin and OAC were randomized to either 6-week clopidogrel therapy (n=307) or 6-month clopidogrel therapy (n=307). The primary endpoint was a composite of death, myocardial infarction (MI), definite stent thrombosis, stroke, or Thrombolysis In Myocardial Infarction (TIMI) major bleeding at 9 months.
  
  
  RESULTS
  The primary endpoint occurred in 30 patients (9.8%) in the 6-week group compared with 27 patients (8.8%) in the 6-month group (hazard ratio [HR]: 1.14; 95% CI: 0.68 to 1.91; p=0.63). There were no significant differences for the secondary combined ischemic endpoint of cardiac death, MI, definite stent thrombosis, and ischemic stroke (12 [4.0%] vs. 13 [4.3%]; HR: 0.93; 95% CI: 0.43 to 2.05; p=0.87) or the secondary bleeding endpoint of TIMI major bleeding (16 [5.3%] vs. 12 [4.0%]; HR: 1.35; 95% CI: 0.64 to 2.84; p=0.44).
  
  
  CONCLUSIONS
  Six weeks of triple therapy was not superior to 6 months with respect to net clinical outcomes. These results suggest that physicians should weigh the trade-off between ischemic and bleeding risk when choosing the shorter or longer duration of triple therapy. (Triple Therapy in Patients on Oral Anticoagulation After Drug Eluting Stent Implantation [ISAR-TRIPLE]; NCT00776633).
authors.affiliation: Deutsches Herzzentrum München, Technische Universität, Klinik für Herz- und Kreislauferkrankungen, Munich, Germany.
authors.forename: Katrin A
authors.initials: KA
authors.lastname: Fiedler
authors.affiliation: Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Michael
authors.initials: M
authors.lastname: Maeng
authors.affiliation: Klinikum der Universität München, Ludwig-Maximilians Universität, Medizinische Klinik und Poliklinik I, Munich, Germany; Deutsches Zentrum für Herz Kreislaufforschung, partner site Munich Heart Alliance, Munich, Germany.
authors.forename: Julinda
authors.initials: J
authors.lastname: Mehilli
authors.affiliation: Deutsches Herzzentrum München, Technische Universität, Klinik für Herz- und Kreislauferkrankungen, Munich, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Schulz-Schüpke
authors.affiliation: Deutsches Herzzentrum München, Technische Universität, Klinik für Herz- und Kreislauferkrankungen, Munich, Germany; Deutsches Zentrum für Herz Kreislaufforschung, partner site Munich Heart Alliance, Munich, Germany.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Byrne
authors.affiliation: Klinikum der Universität München, Ludwig-Maximilians Universität, Medizinische Klinik und Poliklinik I, Munich, Germany; Deutsches Zentrum für Herz Kreislaufforschung, partner site Munich Heart Alliance, Munich, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Sibbing
authors.affiliation: Klinikum rechts der Isar, Technische Universität, I. Medizinische Klinik und Poliklinik, Munich, Germany.
authors.forename: Petra
authors.initials: P
authors.lastname: Hoppmann
authors.affiliation: Klinikum rechts der Isar, Technische Universität, I. Medizinische Klinik und Poliklinik, Munich, Germany.
authors.forename: Simon
authors.initials: S
authors.lastname: Schneider
authors.affiliation: Deutsches Herzzentrum München, Technische Universität, Klinik für Herz- und Kreislauferkrankungen, Munich, Germany.
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Fusaro
authors.affiliation: Deutsches Herzzentrum München, Technische Universität, Klinik für Herz- und Kreislauferkrankungen, Munich, Germany.
authors.forename: Ilka
authors.initials: I
authors.lastname: Ott
authors.affiliation: Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Steen D
authors.initials: SD
authors.lastname: Kristensen
authors.affiliation: Klinikum rechts der Isar, Technische Universität, I. Medizinische Klinik und Poliklinik, Munich, Germany.
authors.forename: Tareq
authors.initials: T
authors.lastname: Ibrahim
authors.affiliation: Klinikum der Universität München, Ludwig-Maximilians Universität, Medizinische Klinik und Poliklinik I, Munich, Germany; Deutsches Zentrum für Herz Kreislaufforschung, partner site Munich Heart Alliance, Munich, Germany.
authors.forename: Steffen
authors.initials: S
authors.lastname: Massberg
authors.affiliation: Deutsches Herzzentrum München, Technische Universität, Klinik für Herz- und Kreislauferkrankungen, Munich, Germany; Deutsches Zentrum für Herz Kreislaufforschung, partner site Munich Heart Alliance, Munich, Germany.
authors.forename: Heribert
authors.initials: H
authors.lastname: Schunkert
authors.affiliation: Deutsches Zentrum für Herz Kreislaufforschung, partner site Munich Heart Alliance, Munich, Germany; Klinikum rechts der Isar, Technische Universität, I. Medizinische Klinik und Poliklinik, Munich, Germany.
authors.forename: Karl-Ludwig
authors.initials: KL
authors.lastname: Laugwitz
authors.affiliation: Deutsches Herzzentrum München, Technische Universität, Klinik für Herz- und Kreislauferkrankungen, Munich, Germany; Deutsches Zentrum für Herz Kreislaufforschung, partner site Munich Heart Alliance, Munich, Germany.
authors.forename: Adnan
authors.initials: A
authors.lastname: Kastrati
authors.affiliation: Klinikum der Universität München, Ludwig-Maximilians Universität, Medizinische Klinik und Poliklinik I, Munich, Germany. Electronic address: n.sarafoff@gmail.com.
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Sarafoff
mesh_terms: D000368:Aged; D001241:Aspirin / Q000008:administration & dosage* / Q000009:adverse effects; D000077144:Clopidogrel; D054855:Drug-Eluting Stents; D005260:Female; D006801:Humans; D008297:Male; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D013988:Ticlopidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin
keywords: aspirin; atrial fibrillation; clopidogrel; percutaneous coronary intervention; vitamin K antagonist