Increased major bleeding risk in patients with kidney dysfunction receiving enoxaparin: a meta-analysis.

PURPOSE: The elimination half-life and consequently the accumulation of enoxaparin increase as glomerular filtration rate (GFR) decreases. A dose adjustment for patients with a GFR <30 ml/min is recommended and considered relatively safe. Our intention was to identify whether the use of enoxaparin is safe and to determine what impact an enoxaparin dose adjustment has on patients with a GFR <60 ml/min. METHODS: A PubMed search and meta-analysis of literature were performed. Studies were analyzed to compare enoxaparin versus other heparins/heparinoids and investigate enoxaparin at different stages of kidney dysfunction. Only controlled trials were considered, and the enoxaparin dose had to be specified. The clinical endpoint was defined as apparent major bleeding. RESULTS: Out of 1,027 publications, 20 studies met the criteria and were analyzed. Our meta-analysis shows that enoxaparin major bleeding complications at a GFR < 60 ml/min increase significantly, with a relative risk (RR) of 1.67 [95% confidence interval (CI) 1.12-2.50) compared with other anticoagulants (p = 0.01). RR for patients on enoxaparin therapy increases exponentially with each stage of chronic kidney disease (CKD stage 1-5) [RR = 0.585 x exp(0.524 x CKD)]. Despite dose adjustment, the major bleeding risk is still significantly increased in patients with a GFR < 60 ml/min versus those with a GFR > 60 ml/min. CONCLUSION: Only patients with a GFR > 60 ml/min can be safely treated with enoxaparin.