Meta-Analysis
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Cardiol. Nov 26, 2020; 12(11): 584-598
Published online Nov 26, 2020. doi: 10.4330/wjc.v12.i11.584
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
Processing time: 89 Days and 9.2 Hours
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; Immune checkpoint inhibitors; Immunotherapy; Cardiovascular adverse events; Pericardial effusion

Core Tip: Cardiovascular immune-related adverse events (irAEs) are rare but potentially life-threatening complications that can occur in patients receiving immune checkpoint inhibitor (ICI) therapy. The most common ICI-associated adverse events are atrial fibrillation, myocarditis, and pericardial effusion. Risk factors for cardiovascular irAEs include treatment with combination immunotherapy, male sex, and a history of cardiac disease. Ongoing post-market surveillance is imperative to characterize long-term risks and improve outcomes among patients receiving ICIs.