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

• Published in: European journal of clinical pharmacology Vol. 68; no. 5; pp. 757 - 765
• Main Authors: Hoffmann, Philipp, Keller, Frieder
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer-Verlag 01.05.2012; Springer; Springer Nature B.V
• Subjects: Anticoagulants; Anticoagulants - adverse effects; Anticoagulants - therapeutic use; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Cardiovascular Diseases - complications; Cardiovascular Diseases - drug therapy; Drug dosages; Enoxaparin - adverse effects; Enoxaparin - therapeutic use; Glomerular Filtration Rate; Hemorrhage; Hemorrhage - chemically induced; Hemorrhage - complications; Hemorrhage - etiology; Hemorrhage - physiopathology; Humans; Kidney diseases; Medical sciences; Meta-analysis; Pharmacoepidemiology and Prescription; Pharmacology; Pharmacology. Drug treatments; Pharmacology/Toxicology; Renal Insufficiency - complications; Renal Insufficiency - physiopathology; Renal Insufficiency, Chronic - complications; Renal Insufficiency, Chronic - physiopathology; Risk; Risk factors; Severity of Illness Index; Enoxaparin; GFR; Kidney dysfunction; Meta analysis; Major bleeding; Bleeding; Human; Low molecular weight heparin; Anticoagulant; Hemorrhage; Enoxaparin sodium; Kidney; Metaanalysis; Urinary system; Dysfunction; Risk factor; Antithrombotic agent
• ISSN: 0031-6970; 1432-1041
• DOI: 10.1007/s00228-011-1149-6

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.