Fixed dose subcutaneous low molecular weight heparins versus adjusted dose unfractionated heparin for venous thromboembolism.
BACKGROUND
Low molecular weight heparins (LMWHs) have been shown to be effective and safe in preventing venous thromboembolism (VTE). They may also be effective for the initial treatment of VTE. This is an update of a Cochrane review first published in 1999 and previously updated in 2004.


OBJECTIVE
To determine the effect of LMWH compared with unfractionated heparin (UFH) for the initial treatment of VTE.


METHODS
Trials were identified by searching the Cochrane Peripheral Vascular Diseases Group Specialised Register and CENTRAL (The Cochrane Library). Colleagues and pharmaceutical companies were contacted for additional information.


METHODS
Randomised controlled trials comparing fixed dose subcutaneous LMWH with adjusted dose intravenous or subcutaneous UFH in people with VTE.


METHODS
Two review authors assessed trials for inclusion and quality, and extracted data independently.


RESULTS
Twenty-three studies were included (n = 9587). Thrombotic complications occurred in 3.6% of participants treated with LMWH compared with 5.3% treated with UFH (odds ratio (OR) 0.70; 95% confidence interval (CI) 0.57 to 0.85). Thrombus size was reduced in 53% of participants treated with LMWH and 45% treated with UFH (OR 0.69; 95% CI 0.59 to 0.81). Major haemorrhages occurred in 1.1% of participants treated with LMWH compared with 1.9% treated with UFH (OR 0.58; 95% CI 0.40 to 0.83). In 19 trials, 4.3% of participants treated with LMWH died compared with 5.8% of participants treated with UFH (OR 0.77; 95% CI 0.63 to 0.93).Nine studies (n = 4451) examined proximal thrombosis, 2192 participants were treated with LMWH and 2259 with UFH. Subgroup analysis showed statistically significant reductions favouring LMWH in thrombotic complications and major haemorrhage. By end of follow up, 80 (3.6%) participants treated with LMWH had thrombotic complications compared with 143 (6.3%) treated with UFH (OR 0.57; 95% CI 0.44 to 0.75). Major haemorrhages occurred in 18 (1.0%) participants treated with LMWH compared with 37 (2.1%) treated with UFH (OR 0.50; 95% CI 0.29 to 0.85). Nine studies showed a statistically significant reduction in mortality favouring LMWH. By the end of follow up, 3.3% (70/2094) of participants treated with LMWH had died and 5.3% (110/2063) treated with UFH.


CONCLUSIONS
Fixed dose LMWH is more effective and safer than adjusted dose UFH for the initial treatment of VTE. Compared to UFH, LMWH significantly reduced the incidence of thrombotic complications, the occurrence of major haemorrhage during initial treatment and overall mortality at follow up.
Erkens
Petra Mg
PM
Department of General Practice, University of Maastricht, Debyeplein 1, Maastricht, Netherlands, 6229 HA.
Prins
Martin H
MH
D006470:Hemorrhage / Q000139:chemically induced; D006493:Heparin / Q000008:administration & dosage / Q000009:adverse effects; D006495:Heparin, Low-Molecular-Weight / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D007279:Injections, Subcutaneous; D011655:Pulmonary Embolism / Q000188:drug therapy* / Q000401:mortality; D016032:Randomized Controlled Trials as Topic; D020246:Venous Thrombosis / Q000188:drug therapy* / Q000401:mortality
D006495:Heparin, Low-Molecular-Weight; D006493:Heparin