Published online before print August 2, 2004, doi: 10.1161/01.CIR.0000138928.83266.24
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(Circulation. 2004;110:874-879.)
© 2004 American Heart Association, Inc.
Original Articles |
Randomized, Placebo-Controlled Trial of Dalteparin for the Prevention of Venous Thromboembolism in Acutely Ill Medical Patients
From the Unité de Pharmacologie Clinique, Université Claude Bernard Lyon I, Lyon, France (A.L.); Department of Academic Medicine, Guy’s, King’s and St Thomas’ School of Medicine, London, UK (A.T.C.); Department of Medicine, Hamilton Health Sciences, General Hospital, Hamilton, Ontario, Canada (A.G.G.T.); Medicinmottagningen, Universitetssjukhuset, Lund, Sweden (C.-G.O.); Cardiology Division, College of Medicine, University of Illinois at Chicago, Chicago, and Medical Development, Pharmacia, Skokie, Ill (P.T.V.); and the Cardiovascular Division, Brigham and Women’s Hospital, Harvard Medical School, Boston, Mass (S.Z.G.).
Correspondence to Alain Leizorovicz, Unité de Pharmacologie Clinique, EA 3736, Université Claude Bernard Lyon I, Rue Guillaume Paradin, 69376 Lyon Cedex 08, France. E-mail al{at}upcl.univ-lyon1.fr
Received October 14, 2003; de novo received January 8, 2004; revision received May 4, 2004; accepted May 7, 2004.
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 (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%).
Conclusions— Dalteparin 5000 IU once daily halved the rate of venous thromboembolism with a low risk of bleeding.
Key Words: anticoagulants • embolism • heparin • prevention • thrombosis
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