Heparin for the prevention of venous thromboembolism in acutely ill medical patients (excluding stroke and myocardial infarction)

Background Venous thromboembolic disease has been extensively studied in surgical patients. The benefit of thromboprophylaxis is now generally accepted, but it is medical patients who make up the greater proportion of the hospital population. Medical patients differ from surgical patients with regard to their health and the pathogenesis of thromboembolism and the impact that preventative measures can have. The extensive experience from thromboprophylaxis studies in surgical patients is therefore not necessarily applicable to non-surgical patients. This is an update of a review first published in 2009. Objectives To determine the effectiveness and safety of heparin (unfractionated heparin or low molecular weight heparin) thromboprophylaxis in acutely ill medical patients admitted to hospital, excluding those admitted to hospital with an acute myocardial infarction or stroke (ischaemic or haemorrhagic) or those requiring admission to an intensive care unit. Search methods For this update the Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (last searched November 2013) and CENTRAL (2013, Issue 10). Selection criteria Randomised controlled trials comparing unfractionated heparin (UFH) or low molecular weight heparin (LMWH) with placebo or no treatment, or comparing UFH with LMWH. Data collection and analysis One review author identified possible trials and a second review author confirmed their eligibility for inclusion in the review. Two review authors extracted the data. Disagreements were resolved by discussion. We performed the meta-analysis using a fixed-effect model with the results expressed as odds ratios (ORs) with 95% confidence intervals (CIs). Main results Sixteen studies with a combined total of 34,369 participants with an acute medical illness were included in this review. We identified 10 studies comparing heparin with placebo or no treatment and six studies comparing LMWH to UFH. Just under half of the studies had an open-label design, putting them at a risk of performance bias. Descriptions of random sequence generation and allocation concealment were missing in most of the studies. Heparin reduced the odds of deep vein thrombosis (DVT) (OR 0.38; 95% CI 0.29 to 0.51; P < 0.00001). The estimated reductions in symptomatic non-fatal pulmonary embolism (PE) (OR 0.46; 95% CI 0.19 to 1.10; P = 0.08), fatal PE (OR 0.71; 95% CI 0.43 to 1.15; P = 0.16) and in combined non-fatal PE and fatal PE (OR 0.65; 95% CI 0.42 to 1.00; P = 0.05) associated with heparin were imprecise. Heparin resulted in an increase in major haemorrhage (OR 1.81; 95% CI 1.10 to 2.98; P = 0.02). There was no clear evidence that heparin had an effect on all-cause mortality and thrombocytopaenia. Compared with UFH, LMWH reduced the risk of DVT (OR 0.77; 95% CI 0.62 to 0.96; P = 0.02) and major bleeding (OR 0.43; 95% CI 0.22 to 0.83; P = 0.01). There was no clear evidence that the effects of LMWH and UFH differed for the PE outcomes, all-cause mortality and thrombocytopaenia. Authors' conclusions The data from this review describe a reduction in the risk of DVT in patients presenting with an acute medical illness who receive heparin thromboprophylaxis. This needs to be balanced against an increase in the risk of bleeding associated with thromboprophylaxis. The analysis favoured LMWH compared with UFH, with a reduced risk of both DVT and bleeding.