Cardiac adverse events of immune checkpoint inhibitors in oncology patients: A systematic review and meta-analysis

World J Cardiol. 2020 Nov 26;12(11):584-598. doi: 10.4330/wjc.v12.i11.584.

Abstract

Background: Immune checkpoint inhibitors (ICIs) are novel therapeutic agents used for various types of cancer. ICIs have revolutionized cancer treatment and improved clinical outcomes among cancer patients. However, immune-related adverse effects of ICI therapy are common. Cardiovascular immune-related adverse events (irAEs) are rare but potentially life-threatening complications.

Aim: To estimate the incidence of cardiovascular irAEs among patients undergoing ICI therapy for various malignancies.

Methods: We conducted this systematic review and meta-analysis by searching PubMed, Cochrane CENTRAL, Web of Science, and SCOPUS databases for relevant interventional trials reporting cardiovascular irAEs. We performed a single-arm meta-analysis using OpenMeta [Analyst] software of the following outcomes: Myocarditis, pericardial effusion, heart failure, cardiomyopathy, atrial fibrillation, myocardial infarction, and cardiac arrest. We assessed the heterogeneity using the I2 test and managed to solve it with Cochrane's leave-one-out method. The risk of bias was performed with the Cochrane's risk of bias tool.

Results: A total of 26 studies were included. The incidence of irAEs follows: Myocarditis: 0.5% [95% confidence interval (CI): 0.1%-0.9%]; Pericardial effusion: 0.5% (95%CI: 0.1%-1.0%); Heart failure: 0.3% (95%CI: 0.0%-0.5%); Cardiomyopathy: 0.3% (95%CI: -0.1%-0.6%); atrial fibrillation: 4.6% (95%CI: 1.0%-14.1%); Myocardial infarction: 0.4% (95%CI: 0.0%-0.7%); and Cardiac arrest: 0.4% (95%CI: 0.1%-0.8%).

Conclusion: The most common cardiovascular irAEs were atrial fibrillation, myocarditis, and pericardial effusion. Although rare, data from post market surveillance will provide estimates of the long-term prevalence and prognosis in patients with ICI-associated cardiovascular complications.

Keywords: Atrial fibrillation; Cancer; Cardiovascular adverse events; Immune checkpoint inhibitors; Immunotherapy; Pericardial effusion.