Thromboprophylaxis with low molecular weight heparin versus unfractionated heparin in intensive care patients: a systematic review with meta-analysis and trial sequential analysis

To compare benefits and harms of low molecular weight heparin (LMWH) versus unfractionated heparin (UFH) as thromboprophylaxis in intensive care unit (ICU) patients. We conducted a systematic review with meta-analysis and trial sequential analysis (TSA) of randomised controlled trials (RCTs) comparing LMWH with UFH as thromboprophylaxis in adult ICU patients. We searched Ovid Medline, PubMed, Embase, Cochrane Library, UpToDate, Guidelines International Network, PROSPERO and the metaRegister of Controlled Trials through 3 December 2014. Random effects risk ratios (RR) and 95 % confidence intervals (CI) were derived for the endpoints deep vein thrombosis (DVT), pulmonary embolism (PE), major bleeding, mortality and net clinical benefit (any DVT, any PE, major bleeding and/or mortality). Eight RCTs (5567 patients) were included, whereof two were considered to have overall low risk of bias. Pooled analyses showed that LMWH compared with UFH reduced the risk of any DVT (RR 0.84, 95 % CI 0.71-0.98, p = 0.03) and resulted in a net clinical benefit (RR 0.90, 95 % CI 0.83-0.97, p = 0.01). There was no statistically significant difference in the risk of any PE (RR 0.65, 95 % CI 0.41-1.03, p = 0.06), major bleeding (RR 0.99, 95 % CI 0.77-1.28, p = 0.96) or mortality (RR 0.93, 95 % CI 0.78-1.12, p = 0.43). TSA supported the results of the conventional analysis on the outcome net clinical benefit but not on risk of any DVT. Evidence from this systematic review revealed a beneficial effect of LMWH compared with UFH when used as thromboprophylaxis in ICU patients.