Circulation, Vol 80, 935-940, Copyright © 1989 by American Heart Association
J Albada, HK Nieuwenhuis and JJ Sixma
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 greater than 3.5) was reached with
coumarins. Thirteen patients in the heparin group and 10 patients in the
Fragmin 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.
ARTICLES
Treatment of acute venous thromboembolism with low molecular weight heparin (Fragmin). Results of a double-blind randomized study
Department of Haematology, University Hospital, Utrecht, The Netherlands.
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