Chest

Chest

Volume 128, Issue 4, October 2005, Pages 2203-2210
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Clinical Investigations
Enoxaparin in the Treatment of Deep Vein Thrombosis With or Without Pulmonary Embolism: An Individual Patient Data Meta-analysis

https://doi.org/10.1378/chest.128.4.2203Get rights and content

Study objectives

Low-molecular-weight heparins have been compared with unfractionated heparin (UFH) for treatment of deep vein thrombosis (DVT). However, a comparison of their efficacy in the presence or absence of pulmonary embolism (PE) has not been studied. We estimated the efficacy and safety of enoxaparin vs UFH in patients with proximal DVT with/without symptomatic PE using a meta-analysis of individual data from randomized controlled trials.

Design and setting

Randomized controlled trials were identified from MEDLINE, EMBASE, abstracts from international meetings on venous thromboembolism (VTE), previous meta-analyses, and trial data provided by the sponsor.

Participants

For inclusion, randomized controlled trials had to be properly randomized; include patients with objectively diagnosed DVT; compare enoxaparin twice daily with UFH; use objective methods to assess recurrent symptomatic VTE, major bleeding, and death at 3 months; and include blind evaluation of clinical events.

Measurements

A meta-analysis was performed using the logarithm of the relative risk (RR) method. Enoxaparin in DVT treatment with/without symptomatic PE was considered noninferior to UFH for preventing VTE at 3 months if the upper limit of the 95% confidence interval (CI) of the RR (enoxaparin/UFH) was lower than a prespecified noninferiority margin (1.61). No increase in major bleeding or mortality should be observed.

Results

The meta-analysis included individual data from three randomized controlled trials (749 patients and 754 patients in the enoxaparin and UFH groups, respectively). The observed RR (enoxaparin/UFH) of VTE was 0.81 (95% CI, 0.52 to 1.26) for the intention-to-treat population (RR, 0.70; 95% CI, 0.43 to 1.13; for per-protocol analysis). Results did not differ for patients with clinical PE (235 patients; RR, 0.84) and without clinical PE (1,268 patients; RR, 0.71), with a nonsignificant heterogeneity test between groups (p = 0.76). A trend in favor of enoxaparin was observed for reduced mortality and major bleeding.

Conclusions

The efficacy and safety of enoxaparin vs UFH for DVT treatment is not modified by the presence of symptomatic PE.

Section snippets

Identification of Randomized Controlled Trials

We attempted to identify all published and unpublished randomized controlled trials that compared enoxaparin with UFH for the treatment of DVT with or without associated symptomatic PE. We searched MEDLINE and EMBASE electronic databases from January 1980 to January 2004 using the following groups of key words: “deep-vein thrombosis” or “thromboembolism” or “pulmonary embolism,” and “randomized” or “randomised” or “controlled trial” or “meta-analysis,” and “UFH” or “LMWH” or “enoxaparin” or

Descriptive Results

A total of five studies1323454647 comparing enoxaparin with UFH for the treatment of DVT were identified. Of these, one trial was excluded because clinical events at 3 months were not reviewed blindly by an independent committee.46 Another study was excluded because included patients presented with PE, with or without associated DVT, rather than DVT with or without associated PE, there was no proper generation of the allocation sequence (alternate odd and even numbers) for randomization and

Discussion

Results from this meta-analysis suggest that in terms of VTE recurrences, major bleeding, and death, enoxaparin is as effective and safe as UFH in the treatment of DVT with or without associated symptomatic PE. Similar results were found when comparing enoxaparin and UFH in patients presenting with a DVT and PE and in patients presenting with DVT alone. Emphasizing the robustness of our results, estimates of treatment effect were unchanged regardless of population considered (intention-to-treat

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    Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestjournal.org/misc/reprints.shtml).

    Funding for this research was provided by Laboratoire Aventis, a subsidiary of the Sanofi Aventis group.

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    Copyright © 2005 The American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.