Copyright
©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
Cardiac adverse events of immune checkpoint inhibitors in oncology patients: A systematic review and meta-analysis
Nso Nso, Daniel Antwi-Amoabeng, Bryce D Beutler, Mark B Ulanja, Jasmine Ghuman, Ahmed Hanfy, Joyce Nimo-Boampong, Sirri Atanga, Rajkumar Doshi, Sostanie Enoru, Nageshwara Gullapalli
Nso Nso, Department of Medicine, Icahn School of Medicine at Mount Sinai, Queens, NY 10029, United States
Daniel Antwi-Amoabeng, Mark B Ulanja, Jasmine Ghuman, Ahmed Hanfy, Rajkumar Doshi, Nageshwara Gullapalli, Department of Internal Medicine, University of Nevada, Reno School of Medicine, Reno, NV 89502, United States
Bryce D Beutler, Department of Radiology, University of Southern California, Keck School of Medicine, Los Angeles, CA 90033, United States
Joyce Nimo-Boampong, Department of Internal Medicine, Warren Alpert Medical School of Brown University, Providence, RI 02903, United States
Sirri Atanga, Department of Medicine, United Health Services Wilson Medical Center, Johnson City, NY 13790, United States
Sostanie Enoru, Department of Cardiovascular Disease, SUNY Downstate Health Science University, Brooklyn, NY 11203, United States
Author contributions: Nso N and Antwi-Amoabeng D contributed equally to this study; Antwi-Amoabeng D conceived the study hypothesis; Nso N analyzed the data; Nso N and Antwi-Amoabeng D designed the study and performed the systematic search, study selection and data extraction; Beutler BD reviewed and edited the initial draft of the manuscript; Ulanja MB assisted with the formal analysis; Ghuman J, Hanfy A and Nimo-Boampong J assisted with data curation; Atanga S assisted with visualization; Doshi R assisted with the formal analysis; Enoru S assisted with validation; Gullapalli N supervised the project from initiation to completion.
Conflict-of-interest statement: The authors declare no actual or potential conflicts of interest.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
http://creativecommons.org/Licenses/by-nc/4.0/ Corresponding author: Bryce D Beutler, MD, Doctor, Department of Radiology, University of Southern California, Keck School of Medicine, 1500 San Pablo St., 2nd Floor, Los Angeles, CA 90033, United States. brycebeutler@hotmail.com
Received: August 28, 2020
Peer-review started: August 28, 2020
First decision: October 5, 2020
Revised: October 12, 2020
Accepted: November 6, 2020
Article in press: November 6, 2020
Published online: November 26, 2020
ARTICLE HIGHLIGHTS
Research background
Immune checkpoint inhibitors (ICIs) are novel antineoplastic agents that are used with increasing frequency throughout the developed world. However, although ICIs have demonstrated remarkable efficacy for the treatment of many malignancies, a range of adverse events have been reported.
Research motivation
Cardiovascular adverse events have been associated with numerous anticancer agents. ICIs have been available for nearly a decade, however, and yet the rate of cardiovascular ICI-related adverse events (irAEs) remains to be definitively established.
Research objectives
We reviewed the medical literature in order to identify, quantify, and characterize the risk of cardiovascular irAEs.
Research methods
We conducted a 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. A total of 26 studies were included.
Research results
New-onset atrial fibrillation was the most common cardiovascular irAE observed among patients taking ICIs, occurring in 4.6% of individuals included in the analysis. Other relatively common cardiovascular adverse events included pericardial effusion and myocarditis, both of which occurred in 0.5% of patients receiving ICI therapy. The mechanism underlying cardiovascular irAEs remains to be definitively established, but it has been hypothesized that T-lymphocyte-mediated inflammation causes direct myocardial injury and disrupts sinoatrial node activity.
Research conclusions
Cardiovascular irAEs—including atrial fibrillation, pericardial effusion, and myocarditis—are uncommon but potentially life-threatening complications of ICI therapy. Mechanisms of pathogenesis and patient- and ICI-associated risk factors warrant further investigation.
Research perspectives
Cardiovascular irAEs represent rare but potentially life-threatening complications of ICIs. Data from post-market surveillance will play a vital role in clarifying the risk of cardiovascular irAEs. Based on the available evidence, however, close cardiac monitoring of patients receiving ICIs may be warranted.
