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Abstract & Commentary
Source: Quinlan DJ, et al. Low-molecular-weight heparin compared with intravenous unfractionated heparin for treatment of pulmonary embolism. Ann Intern Med 2004;140:175.
In this study, the authors performed a meta-analysis of 12 randomized trials comparing the treatment of acute pulmonary embolism (PE) with standard unfractionated heparin (UFH) or one of a variety of low molecular-weight heparin (LMWH) agents. These trials included 1951 patients who were treated for either symptomatic PE or asymptomatic PE in the context of symptomatic deep vein thrombosis (DVT). One thousand twenty-three patients were randomized to receive an LMWH agent and 928 received UFH. Outcomes measured included any recurrent symptomatic venous thromboembolism after treatment and at three months, as well as mortality and bleeding complications. LMWH agents used in these studies included enoxaparin, dalteparin, nadroparin, reviparin, certoparin, and tinzaparin.
In their analysis of the accumulated data, the investigators reported a non-statistically significant decrease in recurrent symptomatic venous thromboembolism at the end of treatment (1.4% vs 2.4%) and at three months (3.0% vs 4.4%) for the LMWH group vs. the UFH group, respectively. In addition, there was no difference in mortality from all causes at the end of treatment (1.4% vs 1.2%) or at three months (4.7% vs 6.1%) for the LMWH and UFH groups, respectively. There also was no difference in rates of major bleeding (1.4% vs 2.3%) or minor bleeding (6.8% vs 5.5%) complications, respectively.
On further analysis, the investigators also found no differences when comparing patients with symptomatic PE vs. those with asymptomatic PE in the setting of DVT in terms of the different treatment arms. Moreover, there was no evidence that any one LMWH agent studied was better or worse than another in terms of efficacy or safety outcomes. Finally, using more advanced statistical methodology such as funnel plotting, the authors report that their outcomes were not influenced excessively by one study and that there was no evidence of major publication bias, indicating that their findings generalize to all the studies investigated in this meta-analysis.
Based on their findings, the authors conclude that LMWH agents appear to be as efficacious and safe as UFH for the initial treatment of patients with acute PE.
Commentary by Theodore C. Chan, MD, FACEP
LMWH agents have distinct advantages when compared with UFH for the treatment of venous thromboembolism. LMWH agents have a more simplified dosing regimen, allowing administration either once or twice daily. Because of their more predictable pharmacokinetics, routine monitoring of coagulation parameters is not required. As a result, the use of these agents has led to outpatient management of patients with DVT. Because of similar pathophysiology, use of these agents for the treatment of acute PE seems reasonable, and this meta-analysis bears out that such an approach is both efficacious and safe.
The findings of this study, however, must be tempered by the fact that, as a meta-analysis, the results ultimately depend on the quality of, as well as differences between, the 12 studies examined. Moreover, the small number of outcome events (i.e., recurrence, bleeding, and death) means that clinically important differences between LMWH and UFH might not have been detected. Finally, six different LMWH agents were studied, which makes comparison with and selection of a specific agent for clinical use less clear.
Finally, while this study indicates that LMWH is at least as efficacious as UFH for the treatment of PE, it did not investigate the potential utility of these agents for outpatient treatment.
Dr. Chan, Associate Clinical Professor of Medicine, Emergency Medicine, University of California, San Diego, is on the Editorial Board of Emergency Medicine Alert.