Cardiovascular safety of the tyrosine kinase inhibitor nintedanib

Pietro Ameri, Giacomo Tini, Paolo Spallarossa, Valentina Mercurio, Carlo Gabriele Tocchetti, Italo Porto

Research output: Contribution to journalReview articlepeer-review

Abstract

The intracellular tyrosine kinase inhibitor nintedanib has shown great efficacy for the treatment of idiopathic pulmonary fibrosis (IPF) and other interstitial lung diseases. However, the incidence rate of myocardial infarction (MI) among participants in landmark IPF trials was remarkable, peaking at 3/100 patient-years. Although subjects with IPF often have a high cardiovascular (CV) risk profile, the occurrence of MI in nintedanib-treated patients may not be fully explained by clustering of CV risk factors. Nintedanib inhibits the vascular endothelial growth factor, platelet-derived growth factor and fibroblast growth factor pathways, which play important roles in the biology of the atherosclerotic plaque and in the response of the heart to ischaemia. Hence, unwanted CV effects may partly account for nintedanib-related MI. We review the evidence supporting this hypothesis and discuss possible actions for a safe implementation of nintedanib in clinical practice, building on the experience with tyrosine kinase inhibitors acquired in cardio-oncology.

Original languageEnglish
JournalBritish Journal of Clinical Pharmacology
DOIs
Publication statusAccepted/In press - 2021

Keywords

  • cardio-oncology
  • cardiovascular risk
  • idiopathic pulmonary fibrosis
  • myocardial infarction
  • nintedanib
  • tyrosine kinase inhibitors

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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