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A Meta-analysis

Anthonie W. A. Lensing, MD, PhD; Martin H. Prins, MD, PhD; Bruce L. Davidson, MD, MPH; Jack Hirsh, MD

Arch Intern Med. 1995;155(6):601-607.

Abstract
Background
An intravenous course of unfractionated heparin adjusted on the basis of the activated partial thromboplastin time is the initial treatment of choice for most patients with venous thromboembolism. Recently introduced low-molecular-weight heparin preparations can be administered subcutaneously, once or twice daily, without laboratory monitoring. We quantitatively assessed the relative efficacy and safety of low-molecular-weight heparin vs standard heparin for the initial treatment of deep venous thrombosis.

Methods
English-language reports of randomized trials were identified through a MEDLINE search (1984 through 1994) and a complementary extensive manual search. Reasons for exclusion from the analysis were no heparin dosage adjustments, the lack of use of objective tests for deep venous thrombosis, duplicate reports, preliminary reports of data later presented in full, dose-ranging studies that used higher doses of low-molecular-weight heparin than are currently in use, and the failure to provide blind end-point assessment. We assessed the incidence of symptomatic recurrent venous thromboembolic disease, the incidence of clinically important bleeding, and mortality.

Results
Ten of the 19 identified trials satisfied the predetermined criteria. The relative risk reductions for symptomatic thromboembolic complications (53% [95% confidence interval, 18% to 73%]), clinically important bleeding (68% [95% confidence interval, 31% to 85%]), and mortality (47% [95% confidence interval, 10% to 69%]) were all statistically significantly in favor of low-molecular-weight heparin.

Conclusions
Low-molecular-weight heparins administered subcutaneously in fixed doses adjusted for body weight and without laboratory monitoring are more effective and safer than adjusted-dose standard heparin. Since low-molecular-weight heparins may not be interchangeable and the conclusions of our meta-analysis are based mainly on the findings of three trials that used two different low-molecular-weight heparins, definitive randomized controlled trials for the other low-molecular-weight heparins are required.

(Arch Intern Med. 1995;155:601-607)

Author Affiliations
From the Center for Haemostasis, Thrombosis, Atherosclerosis, and Inflammation Research and Department of Neurology (Dr Lensing) and Department of Clinical Epidemiology and Biostatistics (Dr Prins), Academic Medical Center, Amsterdam, the Netherlands; Division of Pulmonary and Critical Care Medicine, Hahnemann University, Philadelphia, Pa (Dr Davidson); and Henderson General Division, Hamilton (Ontario) Civic Hospitals Research Center (Dr Hirsh).

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