RE-DEEM: Dabigatran causes no safety concerns in phase II ACS trial
MedWire News: When added to dual anti-platelet therapy (DAT), the orally administered direct thrombin inhibitor (DTI), dabigatran etexilate, results in a “low and acceptable bleeding rate” compared with placebo in patients who have suffered an acute myocardial infarction (MI), according to data presentedat the American Heart Association 2009 Scientific Sessions in, Orlando, Florida, USA.
“Dabigatran up to 150 mg twice daily on top of DAT can be used with modestly increased bleeding risk,” said Jonas Oldgren (Uppsala University Hospital, Sweden). He presented the findings from the phase II RE-DEEM (Randomized Dabigatran Etexilate Dose Finding Study In Patients With Acute Coronary Syndromes [ACS] Post Index Event With Additional Risk Factors For Cardiovascular Complications Also Receiving Aspirin And Clopidogrel) trial.
RE-DEEM was a randomized, double-blind, placebo-controlled dose-escalation study and involved 1861 patients with ST or non-ST elevation MI (60% STEMI; 40% NSTEMI) with at least one additional risk factor for cardiovascular (CV) complications. Four doses of dabigatran were tested against placebo – 50, 75, 110 or 150 mg twice daily – with treatment lasting for 6 months.
The mean age of the patients was 61.8 years and the majority (76%) were male. Just over half (54%) of patients had undergone angioplasty, and nearly all were being treated with aspirin plus clopidogrel at randomization.
The primary outcome of the trial was major bleeding and/or clinically relevant minor bleeding. Major bleeding was defined by the International Society on Thrombosis and Haemostasis (ISTH) as fatal bleeding and/or symptomatic bleeding in a critical area or organ and/or bleeding causing a fall in hemoglobin (Hgb) of ≥20 g/l or leading to transfusion of ≥2 units of whole blood or red cells.
Oldgren reported a dose-dependent response in the frequency of bleeding, with higher percentages of patients treated with the 100 mg and 150 mg dabigatran doses experiencing bleeding, although rates were still low. In an intent-to-treat analysis, the percentage of patients experiencing major bleeding was 2% for placebo, and 3%, 1%, 8%, and 4% for the 50, 75, 110, and 150 mg doses of dabigatran, respectively. The percentage of patients experiencing clinically relevant minor bleeding were 7% for placebo, and 10%, 15%, 24%, and 23% for the four dabigatran doses.
As a secondary outcome measure, and signal of possible anti-thrombotic efficacy, D-dimer levels were measured. Oldgren reported a dramatic decrease in D-dimer levels by 4 weeks with all doses of dabigatran as compared with placebo, with no apparent dose relationship. This effect was maintained for 26 weeks.
Although he stressed the trial was not powered to look at clinical events, Oldgren said that a secondary outcome measure included a composite of CV death, nonfatal MI and stroke. There was an overall low rate of events in the patients treated with the oral DTI.
“RE-DEEM supports the rationale for evaluation of the 100 and 150 mg dabigatran doses on clinical outcome in ACS patients in a larger, adequately powered study,” Oldgren observed.
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By Sara Freeman