Enoxaparin in the treatment of deep vein thrombosis with or without pulmonary embolism: an individual patient data meta-analysis.
OBJECTIVE
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.


METHODS
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.


METHODS
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.


METHODS
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.
Mismetti
Patrick
P
Thrombosis Research Group, Clinical Pharmacology Department, University Hospital Bellevue, F-42055 Saint-Etienne, France.
Quenet
Sara
S
Levine
Mark
M
Merli
Geno
G
Decousus
Hervé
H
Derobert
Eric
E
Laporte
Silvy
S
D000925:Anticoagulants / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D017984:Enoxaparin / Q000627:therapeutic use*; D006495:Heparin, Low-Molecular-Weight / Q000627:therapeutic use; D006801:Humans; D011655:Pulmonary Embolism / Q000188:drug therapy* / Q000209:etiology; D016032:Randomized Controlled Trials as Topic; D012008:Recurrence; D015203:Reproducibility of Results; D012306:Risk; D013923:Thromboembolism / Q000188:drug therapy; D020246:Venous Thrombosis / Q000150:complications / Q000188:drug therapy*
D000925:Anticoagulants; D017984:Enoxaparin; D006495:Heparin, Low-Molecular-Weight