Ciudades

Cite this article as: BMJ, doi:10.1136/bmj.38733.466748.7C (published 26 January 2006)

Research

Efficacy and safety of fondaparinux for the prevention of venous thromboembolism in older acute medical patients: randomised placebo controlled trial
Alexander T Cohen, Bruce L Davidson, Alexander S Gallus, Michael R Lassen, Martin H Prins, Witold Tomkowski, Alexander G G Turpie, Jan F MEgberts, and Anthonie W A Lensing for the ARTEMIS Investigators

Abstract
Objective To determine the efficacy and safety of the anticoagulant fondaparinux in older acute medical inpatients at moderate to high risk of venous thromboembolism. Design Double blind randomised placebo controlled trial. Setting 35 centres in eight countries. Participants 849 medical patients aged 60 or more admitted tohospital for congestive heart failure, acute respiratory illness in the presence of chronic lung disease, or acute infectious or inflammatory disease and expected to remain in bed for at least four days. Interventions 2.5 mg fondaparinux or placebo subcutaneously once daily for six to 14 days. Outcome measure The primary efficacy outcome was venous thromboembolism detected by routine bilateralvenography along with symptomatic venous thromboembolism up to day 15. Secondary outcomes were bleeding and death. Patients were followed up at one month. Results 425 patients in the fondaparinux group and 414 patients in the placebo group were evaluable for safety analysis (10 were not treated). 644 patients (75.9%) were available for the primary efficacy analysis. Venous thrombembolism was detected in5.6% (18/321) of patients treated with fondaparinux and 10.5% (34/323) of patients given placebo, a relative risk reduction of 46.7% (95% confidence interval 7.7% to 69.3%). Symptomatic venous thromboembolism occurred in five patients in the placebo group and none in the fondaparinux group (P = 0.029). Major bleeding occurred in one patient (0.2%) in each group. At the end of follow-up, 14 patientsin the fondaparinux group (3.3%) and 25 in the placebo group (6.0%) had died. Conclusion Fondaparinux is effective in the prevention of asymptomatic and symptomatic venous thromboembolic events in older acute medical patients. The frequency of major bleeding was similar for both fondaparinux and placebo treated patients.

for venous thromboembolism as well as the effectiveness ofthromboprophylaxis in these patients. This uncertainty has limited the systematic application of thromboprophylaxis in this population.7–11 So far only one placebo controlled study has been reported that used bilateral venography to evaluate the presence of venous thromboembolism.12 Fondaparinux, a synthetic, selective inhibitor of factor Xa, effectively reduces postoperative venous thromboembolism afterorthopaedic surgery.13 We carried out a placebo controlled study of fondaparinux in acute medical patients to determine its efficacy and to better document and understand the risk for thrombosis in this large patient group.

Methods
We considered for inclusion in our study acutely ill patients with congestive heart failure class III/IV (New York Heart Association classification), acute respiratoryillness in the presence of chronic lung disease, or clinically diagnosed acute infections or inflammatory disorders such as arthritis, connective tissue diseases, or inflammatory bowel disease. Patients had to be at least 60 years old and expected to remain in bed for at least four days. Exclusion criteria were a high risk for bleeding; acute bacterial endocarditis; cerebral metastasis; recenthaemorrhagic or ischaemic stroke; brain, spinal, or ophthalmological surgery; an indwelling intrathecal or epidural catheter; a serum creatinine level > 180 mol/l in a well hydrated patient; documented hypersensitivity to contrast media; anticipated intubation for more than 24 hours; use of antithrombotics within 48 hours before randomisation; an indication for anticoagulant prophylaxis or therapy;...