No abstract

Background-Considerable variability exists in the use of pharmacological thromboprophylaxis among acutely ill medical patients, partly because clinically relevant end points have not been fully assessed in this population. We undertook an international, multicenter, randomized, double-blind, placebo-controlled trial using clinically important outcomes to assess the efficacy and safety of dalteparin in the prevention of venous thromboembolism in such patients. Methods and Results-Patients (nϭ3706) were randomly assigned to receive either subcutaneous dalteparin 5000 IU daily or placebo for 14 days and were followed up for 90 days. The primary end point was venous thromboembolism, defined as the combination of symptomatic deep vein thrombosis, symptomatic pulmonary embolism, and asymptomatic proximal deep vein thrombosis detected by compression ultrasound at day 21 and sudden death by day 21. The incidence of venous thromboembolism was reduced from 4.96% (73 of 1473 patients) in the placebo group to 2.77% (42 of 1518 patients) in the dalteparin group, an absolute risk reduction of 2.19% or a relative risk reduction of 45% (relative risk, 0.55; 95% CI, 0.38 to 0.80; Pϭ0.0015). The observed benefit was maintained at 90 days. The overall incidence of major bleeding was low but higher in the dalteparin group (9 patients; 0.49%) compared with the placebo group (3 patients; 0.16%). Conclusions-Dalteparin 5000 IU once daily halved the rate of venous thromboembolism with a low risk of bleeding.

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 to hospital 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 bilateral venography 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 in 5.6% (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 patients in 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.

In patients undergoing orthopedic surgery, 2.5 mg of fondaparinux sodium once daily, starting 6 hours postoperatively, showed a major benefit over enoxaparin, achieving an overall risk reduction of VTE greater than 50% without increasing the risk of clinically relevant bleeding.