In patients with atrial fibrillation at risk of stroke (thromboembolism), long-term treatment with idraparinux causes significantly more bleeding than standard treatment with vitamin K antagonists -- despite both treatments having similar efficacy. These are the conclusions of authors of an Article in this week's edition of The Lancet.
Several trials have shown that adjusted-dose anticoagulation therapy with vitamin K antagonists (VKAs) decreases the risk of stroke by about two thirds in these patients -- however this treatment requires regular monitoring and dose adjustment. An unmonitored, fixed-dose anticoagulant regimen would be preferable.
Dr Harry Büller, Department of Vasuclar Medicine, Academic Medical Centre, Amsterdam, Netherlands, and colleagues from the AMADEUS Investigators Group did a trial in which patients were randomised to receive either the anticoagulant idraparinux subcutaneously (2.5mg weekly) or adjusted-dose VKAs.
However, the trial was stopped after randomisation of 4576 patients (2283 idraparinux, 2293 VKAs), and a mean follow-up of 10.7 months because of excess clinically-relevant bleeding with idraparinux -- 346 cases in the idraparinux group versus 226 in the VKA group. (equivalent to 19.7 versus 11.3 per 100 patient-years, or an increase of 74% in the idraparinux group). There were 21 instances of intracranial bleeding with idraparinux and nine with vitamin K antagonists, and elderly patients and those with renal impairment were at greater risk of such complications. In terms of stroke prevention, there were 18 cases of thromboembolism in the idraparinux group and 27 in the VKA group. The number of deaths in both groups were similar -- 61 (idraparinux) versus 62 (VKA).
The authors conclude: "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."
In an accompanying Comment, Dr Alan Go, Kaiser Permanente of Northern Carolina, Oakland, CA, USA, and Dr Daniel Singer, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA, say: "While we wait for the new antithrombotics to emerge, we still need dedicated innovative efforts to improve the delivery of vitamin K antagonists for the growing population with atrial fibrillation."
For Dr Harry Büller, Department of Vasuclar Medicine, Academic Medical Centre, Amsterdam, Netherlands T) +31 20 566 5976 E) h.r.buller@amc.uva.nl
Dr Alan Go, Kaiser Permanente of Northern Carolina, Oakland, CA, USA T) +1 510-891-3553 E) alan.s.go@kp.org
The paper associated with this release can be found at http://multimedia.thelancet.com/pdf/press/VitaminK.pdf.
Journal
The Lancet