AMADEUS

Comparison of idraparinux with vitamin K antagonists for prevention of thromboembolism in patients with atrial fibrillation (2008)

Condition

Prevention of stroke and systemic embolic events in patients with AF

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Objective

To compare the efficacy and safety of idraparinux with conventional anticoagulation with a vitamin K antagonist in the prevention of thromboembolic events

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Trial design

Randomized, open-label non-inferiority phase III trial
Active treatment: idraparinux 2.5 mg s.c. weekly (n=2283)
Control treatment: vitamin K antagonists (warfarin or acenocoumarol) (INR 2.0–3.0) (n=2293)

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Endpoints

Primary efficacy endpoint: cumulative incidence of all strokes and systemic embolism
Secondary endpoints: ischemic stroke, non-ischemic stroke (hemorrhagic and undefined), systemic embolic events, cardiovascular death, myocardial infarction, and VTE
Primary safety endpoint: clinically relevant bleeding (major bleeding and clinically relevant non-major bleeding)

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Trial participants

4576 patients (mean age 72 years) with non-valvular AF and at least one additional risk factor for stroke

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Results

Primary outcome: The trial was stopped after a mean follow-up period of 10.7 months because of excess clinically relevant bleeding with idraparinux. At that time, the primary efficacy endpoint had occurred in 18 of the 2283 patients given idraparinux (0.9% per 100 patient-years) and in 27 of 2293 patients given vitamin K antagonists (1.3% per 100 patient-years) satisfying the non-inferiority criterion. 62 patients in the idraparinux group (3.2% per 100 patient-years) and 61 in the vitamin K antagonist group (2.9% per 100 patient-years) died during follow-up
Safety outcome: Clinically relevant bleeding occurred in 346 patients given idraparinux (19.7% per 100 patient-years) and in 226 patients given a vitamin K antagonist (11.3% per 100 patient-years). Intracranial bleeding was more frequent in the idraparinux group (n=21, 1.1% per 100 patient-years) compared to the vitamin K antagonists group (n=9; 0.4% per 100 patient-years). Elderly patients and those with renal impairment were at greater risk of such complications

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Summary

Efficacy: Long-term treatment with idraparinux was non-inferior to anticoagulation with a vitamin K antagonist in terms of preventing stroke and systemic embolic events
Safety: Treatment with idraparinux caused significantly more clinically relevant bleeding events than conventional treatment with a vitamin K antagonist

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Reference

Bousser MG, Bouthier J, Buller HR, Cohen AT, Crijns H, Davidson BL, Halperin J, Hankey G, Levy S, Pengo V, Prandoni, Prins PMH, Tomkowski W, Thorp-Pedersen C, Wyse DG; the AMADEUS investigators (steering and writing committee). Comparison of idraparinux with vitamin K antagonists for prevention of thromboembolism in patients with atrial fibrillation: a randomised, open-label, non-inferiority trial. Lancet 2008;371:315-321

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Corresponding author

Harry R. Buller, MD, Department of Vascular Medicine, Academic Medical Centre, Meibergdreef 9, 1105 AZ Amsterdam, Netherlands, e-mail: m.m.veendorp@amc.uva.nl

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