Cardiotoxicity associated with immune checkpoint inhibitor therapy: a meta-analysis

Nestor Rubio-Infante, Yoel A. Ramírez-Flores, Elena C. Castillo, Omar Lozano, Gerardo García-Rivas, Guillermo Torre-Amione

Research output: Contribution to journalArticlepeer-review

78 Scopus citations


Aims: This study aimed to estimate the incidence of cardiac immune-related adverse events (irAEs) in patients treated with immune checkpoint inhibitors (ICIs). Methods and results: First, we performed an ICI pharmacovigilance analysis, finding 4.2% of cardiac disorders, including myocarditis, for anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapies. Patients treated with anti-PD-1 antibodies presented a greater number of cardiac adverse events (AEs) than those treated with anti-CTLA-4 (69.4% vs. 20%). Then, we analysed the incidence and characteristics of cardiac irAEs in 1265 papers published prior to 31 August 2020. Of the 4751 patients studied, 1.3% presented cardiac irAEs, with myocarditis being the most frequent (50.8%); 15 patients died (24.6%) due to cardiac irAEs. Finally, we conducted a meta-analysis to determine cardiac irAEs in randomized clinical trials, identified through a systematic search from the database, finding an incidence of 3.1% for ICI monotherapies, 5.8% for dual ICI therapies, 3.7% (irAEs/AEs) for ICIs plus chemotherapy, and cardiac AEs were reported in 2.5% of patients treated solely with chemotherapy. Conclusions: Our study provides precise data for the incidence of cardiac irAEs among patients using ICIs, where despite its low incidence, the high rate of mortality is an important issue to consider. ICIs induce mainly myocarditis at the first doses, and dual therapies seem to provoke higher rates of cardiac irAEs than monotherapies or ICIs plus chemotherapy.

Original languageEnglish (US)
Pages (from-to)1739-1747
Number of pages9
JournalEuropean Journal of Heart Failure
Issue number10
StatePublished - Oct 2021


  • Adverse events
  • CTLA-4
  • Cardiotoxicity
  • Immune checkpoint inhibitors
  • Myocarditis
  • PD-1

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine


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