Dabigatran vs. placebo in patients with acute coronary syndromes on dual antiplatelet therapy: a randomized, double-blind, phase II trial.

Published

Journal Article

AIM: 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. METHODS AND 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.

Full Text

Duke Authors

Cited Authors

  • Oldgren, J; Budaj, A; Granger, CB; Khder, Y; Roberts, J; Siegbahn, A; Tijssen, JGP; Van de Werf, F; Wallentin, L; RE-DEEM Investigators,

Published Date

  • November 2011

Published In

Volume / Issue

  • 32 / 22

Start / End Page

  • 2781 - 2789

PubMed ID

  • 21551462

Pubmed Central ID

  • 21551462

Electronic International Standard Serial Number (EISSN)

  • 1522-9645

Digital Object Identifier (DOI)

  • 10.1093/eurheartj/ehr113

Language

  • eng

Conference Location

  • England