title: New oral anticoagulants in addition to single or dual antiplatelet therapy after an acute coronary syndrome: a systematic review and meta-analysis.
abstract: BACKGROUND
  Oral anticoagulation in addition to antiplatelet treatment after an acute coronary syndrome might reduce ischaemic events but increase bleeding risk. We performed a meta-analysis to evaluate the efficacy and safety of adding direct thrombin or factor-Xa inhibition by any of the novel oral anticoagulants (apixaban, dabigatran, darexaban, rivaroxaban, and ximelagatran) to single (aspirin) or dual (aspirin and clopidogrel) antiplatelet therapy in this setting.
  
  
  RESULTS
  All seven published randomized, placebo-controlled phase II and III studies of novel oral anticoagulants in acute coronary syndromes were included. The database consisted of 30 866 patients, 4135 (13.4%) on single, and 26 731 (86.6%) on dual antiplatelet therapy, with a non-ST- or ST-elevation acute coronary syndrome within the last 7-14 days. We defined major adverse cardiovascular events (MACEs) as the composite of all-cause mortality, myocardial infarction, or stroke; and clinically significant bleeding as the composite of major and non-major bleeding requiring medical attention according to the study definitions. When compared with aspirin alone the combination of an oral anticoagulant and aspirin reduced the incidence of MACE [hazard ratio (HR) and 95% confidence interval 0.70; 0.59-0.84], but increased clinically significant bleeding (HR: 1.79; 1.54-2.09). Compared with dual antiplatelet therapy with aspirin and clopidogrel, adding an oral anticoagulant decreased the incidence of MACE modestly (HR: 0.87; 0.80-0.95), but more than doubled the bleeding (HR: 2.34; 2.06-2.66). Heterogeneity between studies was low, and results were similar when restricting the analysis to phase III studies.
  
  
  CONCLUSIONS
  In patients with a recent acute coronary syndrome, the addition of a new oral anticoagulant to antiplatelet therapy results in a modest reduction in cardiovascular events but a substantial increase in bleeding, most pronounced when new oral anticoagulants are combined with dual antiplatelet therapy.
authors.affiliation: Department of Medical Sciences, Uppsala University, Uppsala, Sweden. jonas.oldgren@ucr.uu.se
authors.forename: Jonas
authors.initials: J
authors.lastname: Oldgren
authors.forename: Lars
authors.initials: L
authors.lastname: Wallentin
authors.forename: John H
authors.initials: JH
authors.lastname: Alexander
authors.forename: Stefan
authors.initials: S
authors.lastname: James
authors.forename: Birgitta
authors.initials: B
authors.lastname: Jönelid
authors.forename: Gabriel
authors.initials: G
authors.lastname: Steg
authors.forename: Johan
authors.initials: J
authors.lastname: Sundström
mesh_terms: D054058:Acute Coronary Syndrome / Q000188:drug therapy*; D000284:Administration, Oral; D000368:Aged; D000925:Anticoagulants / Q000008:administration & dosage* / Q000009:adverse effects; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D004338:Drug Combinations; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome
chemical_list: D000925:Anticoagulants; D004338:Drug Combinations; D010975:Platelet Aggregation Inhibitors
keywords: Acute coronary syndrome; Antiplatelet therapy; Meta-analysis; Myocardial infarction; Oral anticoagulants