New more selective oral anticoagulants – such as direct thrombin and factor Xa inhibitors – have several advantages over vitamin K antagonists. Darexaban, a new direct oral inhibitor of Factor Xa, has been shown to have predictable pharmacokinetics, minimal interaction with food and no drug–drug interactions. Its potential benefit has already been indicated in venous thromboembolic disease and is now being explored in the prevention of stroke in subjects with non-valvular atrial fibrillation. The RUBY-1 trial reported today aimed to explore the safety, tolerability and optimal dosing regimen in the secondary prevention of ischaemic vascular events in subjects with recent ACS.
RUBY-1 was a multicentre, double-blind, randomised, parallel-group study in 1279 patients with recent high-risk non-ST-segment elevation and ST-segment elevation ACS. after discontinuation of parenteral antithrombotic therapy, they received one of six darexaban regimens: 5 mg twice daily (bid), 10 mg once daily (qd), 15 mg bid, 30 mg qd, 30 mg bid or 60 mg qd, or placebo, in addition to dual antiplatelet treatment (aspirin and clopidogrel) for 24 weeks.
The primary outcome of the study (major or clinically relevant non-major bleeding events) was numerically higher in all darexaban arms than in the placebo group (pooled HR 2.275, 95% CI 1.13-4.60, p=0.022). Using placebo as reference (with a bleeding rate of 3.1%), there was a dose-response relationship (p=0.009) for increased bleeding rates with increasing darexaban dose (6.2, 6.5 and 9.3% for 10, 30 and 60 mg daily, respectively). This increase was statistically significant for the 30 mg bid dose (p=0.002).
There was no decrease in rates of efficacy outcome (a composite of death, stroke, myocardial infarction, systemic thromboembolic events and severe recurrent ischaemia) with darexaban versus placebo, but the study was underpowered to evaluate efficacy. There were no other significant drug-related safety concerns associated with darexaban.
Professor Steg, Philippe-Gabriel (Paris, France)
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Notes to editor
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Hot Line III – Acute coronary syndromes
The RUBY-1 Trial: Safety, tolerability and efficacy of YM150, an oral factor Xa inhibitor, in secondary prevention of ischaemic vascular events in patients following an acute coronary syndrome
Edited by the ESC from material supplied by the investigator himself/herself, this press release does not necessarily reflect the opinion of the European Society of Cardiology. The content of the press release has been approved by the investigator.