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[Hepatotoxicity in patients treated with endothelin receptor antagonists: systematic review and meta-analysis of

Diego Macías Saint-Gerons1, César de la Fuente Honrubia1, Dolores Montero Corominas1

  • 1División de Farmacoepidemiología y Farmacovigilancia, Agencia Española de Medicamentos y Productos Sanitarios (AEMPS), Madrid, España.

Medicina Clinica
|April 2, 2013
PubMed
Abstract

Insights

Endothelin receptor antagonists increase the risk of liver injury (hepatotoxicity). This systematic review found a nearly threefold higher risk of hepatic adverse reactions in patients taking these drugs, particularly bosentan.

Area of Science:

  • Pharmacology
  • Hepatology
  • Clinical Trials

Background:

  • Endothelin receptor antagonists (ERAs) are used for conditions like pulmonary arterial hypertension.
  • Concerns exist regarding their potential for liver toxicity.

Purpose of the Study:

  • To systematically evaluate the risk of hepatotoxicity associated with endothelin receptor antagonists.
  • To quantify the risk of liver injury in patients treated with ERAs.

Main Methods:

  • Systematic literature search of PubMed, Cochrane Library, and regulatory agency websites.
  • Inclusion of randomized controlled trials (RCTs) involving bosentan, sitaxentan, or ambrisentan.
  • Meta-analysis of effect sizes using random effects models to calculate relative risks for hepatotoxicity.

Main Results:

  • Twenty-one trials with 3,644 patients were included.
  • A 2.92-fold increased risk of any hepatic adverse reaction was observed (1.85-4.62).
  • A 2.98-fold increased risk of significant liver enzyme elevations (≥3x ULN) was found (1.69-5.25).

Conclusions:

  • Endothelin receptor antagonists are associated with an increased risk of hepatotoxicity.
  • Limited data for ERAs other than bosentan preclude definitive conclusions on individual drug risks.
Keywords:
AmbrisentanAmbrisentánBosentanBosentánDaño hepáticoEnsayo clínico aleatorizado y controladoHepatic eventHepatotoxicidadHepatotoxicityLiver injuryMeta-analysisMetaanálisisRandomized controlled trialReacción hepáticaSitaxentanSitaxentánSitaxsentanSitaxsentán

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