Mismetti P, Laporte S, Darmon J Y, Buchmüller A, Decousus H
Thrombosis Research Group, Clinical Pharmacology Unit, University Hospital, Saint-Etienne and Medibridge Clinical Research, Velizy, France.
Br J Surg. 2001 Jul;88(7):913-30. doi: 10.1046/j.0007-1323.2001.01800.x.
Low molecular weight heparins (LMWHs) have become routine thromboprophylaxis in general surgery. However, their actual clinical effect, its magnitude relative to that of unfractionated heparin (UFH), and the optimal dose are still debated.
A meta-analysis was performed of all available randomized trials in general surgery comparing LMWH with placebo or no treatment, or with UFH.
Comparison versus placebo or no treatment confirmed that the significant reduction in asymptomatic deep vein thrombosis (DVT) obtained with LMWH (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 embolism (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 LMWH, 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 slightly superior efficacy but increased haemorrhagic risk, including that of major haemorrhage.
Asymptomatic DVT may be regarded as a reliable surrogate endpoint for clinical outcome in studies investigating thromboprophylaxis in general surgery. LMWH seems to be as effective and safe as UFH. Determination of the optimal dose regimen of LMWH for this indication requires further investigation.
低分子量肝素(LMWHs)已成为普通外科常规的血栓预防用药。然而,其实际临床效果、相对于普通肝素(UFH)的效果大小以及最佳剂量仍存在争议。
对普通外科中所有比较LMWH与安慰剂或不治疗,或与UFH的随机试验进行荟萃分析。
与安慰剂或不治疗相比,证实LMWH(n = 513;相对危险度(RR)0.28(95%置信区间0.14 - 0.54))使无症状深静脉血栓形成(DVT)显著减少,这与临床肺栓塞(n = 5456;RR 0.25(0.08 - 0.79))和临床静脉血栓栓塞(VTE)(n = 4890;RR 0.29(0.11 - 0.73))显著减少以及总体死亡率有降低趋势相关。与UFH相比显示出有利于LMWH的趋势,临床VTE显著减少(P = 0.049),在癌症手术中也发现了这种趋势。低于3400抗Xa单位剂量的LMWH似乎与UFH一样有效且更安全,而较高剂量产生稍优的疗效但增加了出血风险,包括大出血风险。
在普通外科血栓预防研究中,无症状DVT可被视为临床结局的可靠替代终点。LMWH似乎与UFH一样有效且安全。确定该适应证下LMWH的最佳剂量方案需要进一步研究。