Meta-analysis of low molecular weight heparin in the prevention of venous thromboembolism in general surgery

Background: Low molecular weight heparins (LMWHs) have become routine throm boprophylaxis in general surgery. However, their actual clinical effect, it s magnitude relative to that of unfractionated heparin (UFH), and the optim al dose are still debated. Methods: A meta-analysis was performed of all available randomized trials i n general surgery comparing LMWH with placebo or no treatment, or with UFH. Results: Comparison versus placebo or no treatment confirmed that the signi ficant reduction in asymptomatic deep vein thrombosis (DVT) obtained with L MWH (n = 513; relative risk (RR) 0.28 (95 per cent confidence interval 0.14 -0.54)) was associated with a significant reduction in clinical pulmonary e mbolism (n = 5456; RR 0.25 (0.08-0.79)) and clinical venous thromboembolism (VTE) (n = 4890; RR 0.29 (0.11-0.73)), and a trend towards a reduction in overall mortality rate. Comparison versus UFH showed a trend in favour of L MWH, with a significant reduction in clinical VTE (P = 0.049), a trend also found for cancer surgery. LMWH at doses below 3400 anti-Xa units seemed to be as effective as, and safer than, UFH, while higher doses yielded slight ly superior efficacy but increased haemorrhagic risk, including that of maj or haemorrhage. Conclusion: Asymptomatic DVT may be regarded as a reliable surrogate endpoi nt for clinical outcome in studies investigating thromboprophylaxis in gene ral surgery. LMWH seems to be as effective and safe as UFH. Determination o f the optimal dose regimen of LMWH for this indication requires further inv estigation.