Fixed dose subcutaneous low molecular weight heparins versus adjusted dose unfractionated heparin for venous thromboembolism

Abstract

Background: Low molecular weight heparins (LMWH) have been shown to be effective and safe in preventing venous thromboembolism (VTE), and may also be effective for the initial treatment of VTE.

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

Search strategy: Trials were identified from the Cochrane Peripheral Vascular Diseases Group's Specialised Register, CENTRAL and LILACS. Colleagues and pharmaceutical companies were contacted for additional information.

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

Data collection and analysis: At least two reviewers assessed trials for inclusion and quality, and extracted data independently.

Main results: Twenty-two studies were included (n = 8867). Thrombotic complications occurred in 151/4181 (3.6%) participants treated with LMWH, compared with 211/3941 (5.4%) participants treated with UFH (odds ratio (OR) 0.68; 95% confidence intervals (CI) 0.55 to 0.84, 18 trials). 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, 12 trials). Major haemorrhages occurred in 41/3500 (1.2%) participants treated with LMWH, compared with 73/3624 (2.0%) participants treated with UFH (OR 0.57; 95% CI 0.39 to 0.83, 19 trials). In eighteen trials, 187/4193 (4.5%) participants treated with LMWH died, compared with 233/3861 (6.0%) participants treated with UFH (OR 0.76; 95% CI 0.62 to 0.92). Nine studies (n = 4451) examined proximal thrombosis; 2192 participants treated with LMWH and 2259 with UFH. Subgroup analysis showed statistically significant reductions favouring LMWH in thrombotic complications and major haemorrhage. By the 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 haemorrhage 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 (n = 4157) showed a statistically significant reduction favouring LMWH with respect to mortality. By the end of follow up, 3.3% (70/2094) of participants treated with LMWH had died, compared with 5.3% (110/2063) of participants treated with UFH (OR 0.62; 95% CI 0.46 to 0.84).

Reviewers' conclusions: LMWH is more effective than UFH for the initial treatment of VTE. LMWH significantly reduces the occurrence of major haemorrhage during initial treatment and overall mortality at follow up.