Lancet: New drug shows same hemorrhage rates, more bleeding for AF patients

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In patients with atrial fibrillation at risk for thromboembolism, long-term treatment with idraparinux was no worse than vitamin K antagonists in terms of efficacy, but caused significantly more bleeding, according to the Jan. 26 issue of the Lancet.

Idraparinux, manufactured by Sanofi-Aventis and Organon, is part of a synthetic oligosaccharide family of anticoagulant drugs, indicated for the treatment and secondary prevention of venous thromboembolism (VTE), as well as the prevention of thromboembolic events associated with atrial fibrillation (AF).

Vitamin K antagonists are the current gold-standard treatment for prophylaxis against stroke and systemic embolism in patients with AF, which requires regular monitoring and dose adjustment. The researchers said an unmonitored fixed-dose anticoagulant regimen would be preferable.

The aim of the randomized, open-label non-inferiority trial was to compare the efficacy and safety of idraparinux with vitamin K antagonists, according to Marie-Germaine Bousser, MD, of the neurology department at the Hospital Lariboisiere in Paris, and colleagues.

The researchers randomly assigned patients with AF at risk for thromboembolism to receive either subcutaneous idraparinux (2.5 mg weekly) or adjusted-dose vitamin K antagonists (target of an international normalized ratio of 2-to-3).

The authors said the assessment of outcome was done blinded to treatment. The primary efficacy outcome was the cumulative incidence of all stroke and systemic embolism, and the principal safety outcome was clinically relevant bleeding.

Bousser and colleagues randomized 4,576 patients (2,283 to receive idraparinux, 2,293 to receive vitamin K antagonists) and a mean follow-up period of 10.7 months because of excess clinically relevant bleeding with idraparinux (346 cases vs 226 cases; 19.7 vs 11.3 per 100 patient-years).

The researchers found 21 instances of intracranial bleeding with idraparinux and nine with vitamin K antagonists (1.1 vs. 0.4 per 100 patient-years); elderly patients and those with renal impairment were at greater risk of such complications. There were 18 cases of thromboembolism with idraparinux and 27 cases with vitamin K antagonists (0.9 vs. 1.3 per 100 patient-years), satisfying the non-inferiority criterion. There were 62 deaths with idraparinux and 61 with vitamin K anatagonists, according to the authors.

The authors found that despite a significantly higher rate of fatal hemorrhage in patients treated with idraparinux, there was no difference between the two treatments in overall mortality, the result of an imbalance in fatal cardiovascular events other than stroke, hemorrhage, or myocardial infarction.

Sanofi-Aventis funded the study.