title: Risk and Benefits of Triple Therapy in Patients Undergoing Coronary Stent Implantation Requiring Oral Anticoagulation: A Meta-Analysis of 16 Studies.
abstract: BACKGROUND
  Patients with coronary artery disease who undergo stent implantation and have concomitant indication for long-term oral anticoagulation represent a considerable proportion of the overall population. To date there is still no consensus about the optimal antithrombotic strategy to choose in this kind of patients, due to the difficult balance between an increased risk of bleeding and thromboembolic complications. Therefore, the aim of this study was to perform a meta-analysis to evaluate the risk and benefits of triple antithrombotic therapy versus dual antithrombotic therapy in patients undergoing coronary stent implantation, requiring long-term oral anticoagulation.
  
  
  METHODS
  We performed formal searches of PubMed, EMBASE, Cochrane central register of controlled trials and major international scientific session abstracts from January 1990 to September 2015 regarding the use of triple antithrombotic therapy (TT) versus dual therapy (DT) in patients undergoing percutaneous coronary stent implantation that required chronic oral anticoagulation. Data regarding study design, inclusion/exclusion criteria, number of patients, and selected endpoints was extracted by 2 investigators. Disagreements were resolved by consensus.
  
  
  RESULTS
  Sixteen trials with a total of 21716 patients undergoing coronary stent implantation with indication to long term oral anticoagulation, were finally included. A total of 6950 received TT, whereas 14766 received DT alone. The follow-up period ranged from 180 to 730 days. Data regarding mortality were available in 21658 patients (99.7 %). All cause mortality was observed in 10.4 % patients in TT versus 16.3 % in DT (OR [95 % CI] =0.73 [0.66-0.80], p <0.001; phet<0.001). In addition, TT was associated with a reduced incidence of MI (6.4 versus 9.8 %, OR [95 % CI] = 0.74 [0.65-0.84], p < 0.001; phet< 0.001) and ischemic stroke (1.8 versus 3.9 %, OR [95 % CI] = 0.55 [0.45-0.68], p < 0.001; phet= 0.07). As expected, TT was associated with a significant increase in major bleeding events (10.8 versus 8.5 %, OR [95 % CI] = 1.38 [1.25-1.53], p < 0.001; phet= 0.02). By meta regression analysis we found that benefits in mortality with TT were inversely related with the risk of bleedings (beta [95 % CI] = 2.25 (1.55; 2.95), p < 0.00001). The benefits with TT regarding overall mortality, recurrent MI and ischemic stroke were also confirmed in a pre-specified analysis versus DAPT or oral anticoagulation in association with a single antiplatelet agent.
  
  
  CONCLUSIONS
  This meta-analysis showed that among patients undergoing coronary stent implantation, requiring chronic OAC, the use of a TT is associated with a significant reduction in overall mortality, recurrent MI and ischemic stroke. As expected, we found a higher incidence of bleedings in patients treated with triple therapy. The benefits in mortality were lost in patients at high-risk for bleedings.
authors.affiliation: Division of Cardiology, Azienda Ospedaliera-Universitaria "Maggiore della Carità", Eastern Piedmont University, C.so Mazzini, 18, 28100, Novara, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Barbieri
authors.affiliation: Division of Cardiology, Azienda Ospedaliera-Universitaria "Maggiore della Carità", Eastern Piedmont University, C.so Mazzini, 18, 28100, Novara, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Verdoia
authors.affiliation: Division of Cardiology, Azienda Ospedaliera-Universitaria "Maggiore della Carità", Eastern Piedmont University, C.so Mazzini, 18, 28100, Novara, Italy.
authors.forename: Alon
authors.initials: A
authors.lastname: Schaffer
authors.affiliation: Department of Cardiology, UMC St Radboud, Nijmegen, The Netherlands.
authors.forename: Harry
authors.initials: H
authors.lastname: Suryapranata
authors.affiliation: Division of Cardiology, Azienda Ospedaliera-Universitaria "Maggiore della Carità", Eastern Piedmont University, C.so Mazzini, 18, 28100, Novara, Italy. giuseppe.deluca@maggioreosp.novara.it.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: De Luca
mesh_terms: D000925:Anticoagulants / Q000008:administration & dosage* / Q000627:therapeutic use; D001241:Aspirin / Q000008:administration & dosage / Q000627:therapeutic use; D000077144:Clopidogrel; D003324:Coronary Artery Disease / Q000188:drug therapy* / Q000453:epidemiology / Q000601:surgery; D004358:Drug Therapy; D005343:Fibrinolytic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D006470:Hemorrhage / Q000139:chemically induced / Q000453:epidemiology; D006801:Humans; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage* / Q000627:therapeutic use; D012306:Risk; D015607:Stents; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000627:therapeutic use; D014859:Warfarin / Q000008:administration & dosage / Q000627:therapeutic use
chemical_list: D000925:Anticoagulants; D005343:Fibrinolytic Agents; D010975:Platelet Aggregation Inhibitors; D014859:Warfarin; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin
keywords: Bleedings; Thromboembolic complications; Triple therapy