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

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.

Venous thromboembolism in hematopoietic stem cell transplant recipients

“…The International Myeloma Working group and ASCO recommend prophylaxis with either aspirin or LMWH for lower risk patients, and LMWH for higher risk patients receiving thalidomide or lenalidomide. 47,61 Hospitalized patients Based on randomized clinical trials of thromboprophylaxis in medically ill hospitalized patients, 62,63 and a meta-analysis that demonstrated 40% lower rates of VTE with pharmacologic prophylaxis versus placebo, 64 the current ACCP 52 and ASCO guidelines 47 strongly recommend thromboprophylaxis in hospitalized medically ill and cancer patients, respectively. However, trials of thromboprophylaxis did not include HSCT patients who are not specifically included in these recommendations.…”

Venous thromboembolism prophylaxis in medically ill patients and the development of strategies to improve prophylaxis rates

“…Three large-scale prevention studies involving over 5,500 medically ill patients have shown that 11-15% and 4-5% of patients will have venous thromboembolism and proximal deep vein thrombosis, respectively, identified by screening studies in the absence of prophylaxis [3][4][5]. Additionally, the national DVT Free Registry found that 60% of patients diagnosed with an acute DVT were in the peri-hospitalization period.…”

The true treatment benefit is unpredictable in clinical trials using surrogate outcome measured with diagnostic tests

“…An empirical example of the underestimation of treatment effect by I-Fibrinogen scanning compared to venography has been shown by Rodgers [43]. Ultrasonography has been recently used in clinical trials but is not yet generalized for detecting asymptomatic DVTs without confirmatory venography [44].…”