Treatment of acute venous thromboembolism with low molecular weight heparin (Fragmin). Results of a double-blind randomized study.

Abstract

We performed a prospective, randomized, double-blind trial in 194 unselected patients to determine the safety and efficacy of low molecular weight heparin (Fragmin) compared with standard heparin as the initial treatment of acute venous thromboembolism. Ninety-eight patients received continuous intravenous heparin, and 96 patients received Fragmin for 5-10 days. Doses were adjusted to maintain anti-Xa levels between 0.3 and 0.6 unit/ml for patients with a high risk for a bleeding complication and between 0.4 and 0.9 unit/ml for patients with a low risk for bleeding. Treatment was stopped when a therapeutic level of anticoagulation (International Normalized Ratio > 3.5) was reached with coumarins. Thirteen patients in the heparin group and 10 patients in the Fragman group had a major bleeding complication. The incidence of major and minor bleeding complications combined decreased from 48.9% to 38.5% (95% confidence interval for the difference, -3.5% to +24.2%), corresponding with a relative bleeding risk reduction of 21.2%. There were no significant differences in efficacy as defined by new high-probability defects on repeat ventilation-perfusion scintigraphy of the lung in 80 patients: six of 46 patients in the heparin group and 3 of 34 patients in the Fragmin group had new defects (95% confidence interval for the difference, -9.4% to +17.8%). We conclude that low molecular weight heparin (Fragmin) given in adjusted, continuous, and intravenous doses is safe and effective as initial treatment of acute venous thromboembolism compared with heparin. There is a trend in risk reduction for bleeding in favor of low molecular weight heparin, a trend, however, that is smaller than expected compared with animal studies.