51. [Hepatotoxicity in patients treated with endothelin receptor antagonists: systematic review and meta-analysis of randomized clinical trials].
- Author
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Macías Saint-Gerons D, de la Fuente Honrubia C, Montero Corominas D, and Catalá-López F
- Subjects
- Antihypertensive Agents therapeutic use, Biomarkers blood, Bosentan, Chemical and Drug Induced Liver Injury blood, Chemical and Drug Induced Liver Injury epidemiology, Endothelin Receptor Antagonists therapeutic use, Humans, Hypertension drug therapy, Isoxazoles adverse effects, Isoxazoles therapeutic use, Phenylpropionates adverse effects, Phenylpropionates therapeutic use, Pyridazines adverse effects, Pyridazines therapeutic use, Randomized Controlled Trials as Topic, Safety-Based Drug Withdrawals, Sulfonamides adverse effects, Sulfonamides therapeutic use, Thiophenes adverse effects, Thiophenes therapeutic use, Transaminases blood, Antihypertensive Agents adverse effects, Chemical and Drug Induced Liver Injury etiology, Endothelin Receptor Antagonists adverse effects
- Abstract
Background and Objective: We evaluated the risk of hepatotoxicity associated to endothelin receptor antagonists., Patients and Method: Systematic searches in PubMed/MEDLINE, the Cochrane Library as well as regulatory agencies websites were performed. Randomized controlled trials in patients receiving endothelin receptor antagonists (bosentan, sitaxentan or ambrisentan) in at least one treatment group were included. Prior to data extraction, definitions of hepatotoxicity were established. Effect sizes with 95% confidence intervals were calculated using random effects models. Heterogeneity was analysed using Cochran's Q and I(2) tests. Publication bias was assessed using Egger's method and funnel plots were generated., Results: Twenty-one trials met the inclusion criteria (3,644 patients). Bosentan was the evaluated drug in 1,689 (74%) patients who received endothelin receptor antagonists. Compared with controls, relative risk for any hepatic adverse reaction was 2.92 (1.85-4.62; I(2)=30.6%). When hepatotoxicity was defined as elevations of liver alanine or aspartate aminotransferases equal or greater than 3 times the upper limit of normal, relative risk was 2.98 (1.69-5.25; I(2) = 40.9%). No evidence of publication bias was found (Egger's method: p = 0.68)., Conclusions: Our results suggest an increased risk of hepatotoxicity in patients receiving endothelin receptor antagonists. Given the limited data available for endothelin receptor antagonists other than bosentan, it is not possible to draw firm conclusions about the individual risk associated for the remaining endothelin receptor antagonists., (Copyright © 2012 Elsevier España, S.L. All rights reserved.)
- Published
- 2014
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