Randomized, Placebo-Controlled Trial of Dalteparin for the Prevention of Venous Thromboembolism in Acutely Ill Medical Patients

TLDR

Variability in pharmacologic thromboprophylaxis for acutely ill medical patients stems from incomplete assessment of clinically relevant endpoints. This international, multicenter, double‑blind, placebo‑controlled trial evaluated the efficacy and safety of dalteparin for preventing venous thromboembolism in such patients. Patients (n=3706) received daily subcutaneous dalteparin 5000 IU or placebo for 14 days, with the primary endpoint defined as symptomatic or asymptomatic proximal deep‑vein thrombosis, pulmonary embolism, or sudden death by day 21. Dalteparin lowered venous thromboembolism from 4.96 % to 2.77 % (a 45 % relative risk reduction) while maintaining a low but slightly higher major‑bleeding rate versus placebo.

Abstract

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.Patients (n=3706) 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; P=0.0015). 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%).Dalteparin 5000 IU once daily halved the rate of venous thromboembolism with a low risk of bleeding.