title: Dabigatran vs. placebo in patients with acute coronary syndromes on dual antiplatelet therapy: a randomized, double-blind, phase II trial.
abstract: OBJECTIVE
  After an acute coronary syndrome, patients remain at risk of recurrent ischaemic events, despite contemporary treatment, including aspirin and clopidogrel. We evaluated the safety and indicators of efficacy of the novel oral direct thrombin inhibitor dabigatran.
  
  
  RESULTS
  In this double-blind, placebo-controlled, dose-escalation trial, 1861 patients (99.2% on dual antiplatelet treatment) in 161 centres were enrolled at mean 7.5 days (SD 3.8) after an ST-elevation (60%) or non-ST-elevation (40%) myocardial infarction and randomized to twice daily treatment with dabigatran 50 mg (n = 369), 75 mg (n = 368), 110 mg (n = 406), 150 mg (n = 347), or placebo (n = 371). Primary outcome was the composite of major or clinically relevant minor bleeding during the 6-month treatment period. There were 96 primary outcome events and, compared with placebo, a dose-dependent increase with dabigatran, hazard ratio (HR) 1.77 (95% confidence intervals 0.70, 4.50) for 50 mg; HR 2.17 (0.88, 5.31) for 75 mg; HR 3.92 (1.72, 8.95) for 110 mg; and HR 4.27 (1.86, 9.81) for 150 mg. Compared with placebo, D-dimer concentrations were reduced in all dabigatran dose groups by an average of 37 and 45% at weeks 1 and 4, respectively (P< 0.001). Fourteen (3.8%) patients died, had a myocardial infarction or stroke in the placebo group compared with 17 (4.6%) in 50 mg, 18 (4.9%) in 75 mg, 12 (3.0%) in 110 mg, and 12 (3.5%) in the 150 mg dabigatran groups.
  
  
  CONCLUSIONS
  Dabigatran, in addition to dual antiplatelet therapy, was associated with a dose-dependent increase in bleeding events and significantly reduced coagulation activity in patients with a recent myocardial infarction.
authors.affiliation: Uppsala Clinical Research Center and Department of Medical Sciences,  Uppsala University, S-751 85 Uppsala,  Sweden.
authors.forename: Jonas
authors.initials: J
authors.lastname: Oldgren
authors.forename: Andrzej
authors.initials: A
authors.lastname: Budaj
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Granger
authors.forename: Yasser
authors.initials: Y
authors.lastname: Khder
authors.forename: Juliet
authors.initials: J
authors.lastname: Roberts
authors.forename: Agneta
authors.initials: A
authors.lastname: Siegbahn
authors.forename: Jan G P
authors.initials: JG
authors.lastname: Tijssen
authors.forename: Frans
authors.initials: F
authors.lastname: Van de Werf
authors.forename: Lars
authors.initials: L
authors.lastname: Wallentin
mesh_terms: D054058:Acute Coronary Syndrome / Q000188:drug therapy*; D000368:Aged; D001241:Aspirin / Q000008:administration & dosage / Q000009:adverse effects; D001562:Benzimidazoles / Q000008:administration & dosage* / Q000009:adverse effects; D000077144:Clopidogrel; D000069604:Dabigatran; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004338:Drug Combinations; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism; D005343:Fibrinolytic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D011446:Prospective Studies; D012008:Recurrence; D013988:Ticlopidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D016896:Treatment Outcome; D015091:beta-Alanine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*
chemical_list: D001562:Benzimidazoles; D004338:Drug Combinations; D005338:Fibrin Fibrinogen Degradation Products; D005343:Fibrinolytic Agents; D010975:Platelet Aggregation Inhibitors; C036309:fibrin fragment D; D015091:beta-Alanine; D000077144:Clopidogrel; D000069604:Dabigatran; D013988:Ticlopidine; D001241:Aspirin