ORIGINAL RESEARCH article
Front. Cardiovasc. Med.
Sec. Cardiovascular Pharmacology and Drug Discovery
Disproportionality Analysis of Adverse Events Associated with Endothelin Receptor Antagonists Based on the FDA Adverse Event Reporting System (FAERS)
Sitian Li
Liao Jianting
Qinan Yin
Changli He
Yin Wang
Gang Li
Lizhu Han
Bian Yuan
Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, China
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Abstract
Background: Endothelin receptor antagonists (ERAs)—bosentan, ambrisentan, macitentan—are first-line for pulmonary arterial hypertension (PAH), yet real-world comparative safety data are scarce. Objective: Mine FAERS to identify and contrast potential ADEs across the three ERAs. Methods: Retrospective disproportionality analysis of ICSRs (Q1 2004–Q2 2025) followed READUS-PV; MedDRA-coded events were screened with ROR, PRR, BCPNN, MGPS (≥2 algorithms required for signal) and TTO curves. Results: 35 112, 48 411, 29 877 reports were extracted for bosentan, ambrisentan, macitentan (female 74%, 18–65 y). Ambrisentan contributed 42.7% of cases. Labelled signals—peripheral oedema, dyspnoea, liver dysfunction, anaemia—were confirmed; novel signals included jaw pain, pulmonary thrombosis, gout, hypokalaemia, hypotension. Most events arose within the first year; >50% of flagged PTs occurred ≥12 months after initiation. Conclusion: The study validates known toxicities, ranks their relative intensity and flags new ADEs, supporting individualized ERA selection and prolonged monitoring of hepatic, renal, haemodynamic and electrolyte status.
Summary
Keywords
Adverse DrugEvents, Disproportionality analysis, Endothelin receptor antagonists, pulmonary arterial hypertension, Signal detection
Received
25 September 2025
Accepted
10 February 2026
Copyright
© 2026 Li, Jianting, Yin, He, Wang, Li, Han and Yuan. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Lizhu Han; Bian Yuan
Disclaimer
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