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

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Abstract

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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 methods

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).

Authors' 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.

PICOs

Population
Intervention
Comparison
Outcome

The PICO model is widely used and taught in evidence-based health care as a strategy for formulating questions and search strategies and for characterizing clinical studies or meta-analyses. PICO stands for four different potential components of a clinical question: Patient, Population or Problem; Intervention; Comparison; Outcome.

See more on using PICO in the Cochrane Handbook.

Plain language summary

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

Treating blood clots in the deep veins and lungs with low molecular weight heparin (LMWH) results in fewer haemorrhages and deaths than treatment with unfractionated heparin. Blood clots can form after surgery, bed‐rest or spontaneously. These can block veins and may be fatal if they move into the lungs. Heparin is a drug that thins the blood. When people have clots in the deep veins or lungs, heparin is generally used for the first stage of treatment. Older styles of heparin are called 'unfractionated heparin', and newer types are called 'low molecular weight heparin' (LMWH). This review of trials found that LMWH is at least as good as unfractionated heparin for treating clots and preventing their recurrence. It is also better at preventing haemorrhages and deaths.