Dabigatran vs. placebo in patients with acute coronary syndromes on dual
antiplatelet therapy: a randomized, double-blind, phase II trial.
Author(s): Oldgren J, Budaj A, Granger CB, Khder Y, Roberts J, Siegbahn A, Tijssen JG, Van
de Werf F, Wallentin L; RE-DEEM Investigators.
Affiliation(s): Uppsala Clinical Research Center and Department of Medical Sciences, Uppsala
University, S-751 85 Uppsala, Sweden.
Publication date & source: 2011, Eur Heart J. , 32(22):2781-9
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.
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