Immune checkpoint inhibitors: Unravelling atherosclerotic cardiovascular risk.

Gray, Rhys; Manisty, Charlotte; Cheng, Richard; Dastidar, Amardeep; Mamas, Mamas; Ghosh, Arjun

Abstract

1. Introduction
The development of immune checkpoint inhibitors (ICI) has transformed the landscape of cancer treatment in the past decade with these agents becoming the standard of care in the treatment of many malignancies [1]. There are currently more than 125 indications for ICI use in the adjuvant and neoadjuvant settings, including some as first-line therapy, in more than 20 distinct cancer types [2]. Almost half of all patients with metastatic cancer in high-income countries are now being treated with ICIs [1]. Additionally, novel targets for immune checkpoint inhibition and indications for use are increasing [3].
Immune checkpoints play a role in controlling auto reactivity and therefore have a toxicity profile of known immune-related adverse events (irAEs) that may potentially affect any organ or system, including the cardiovascular system [4]. Initially, ICI-related cardiovascular (CV) events focused on myocarditis and pericardial disease; however, recent data have expanded this association to include heart failure, conduction abnormalities, venous thrombosis, vasculitis, and atherosclerotic events [2]. Initially, atherosclerotic CV events such as acute myocardial infarction (MI), stroke, and peripheral arterial disease were not specifically recognised as irAEs and therefore not considered as a possible toxicity of ICIs. However, there is now growing preclinical and clinical evidence suggesting that ICIs may accelerate atherosclerosis and lead to an increased risk of atherosclerotic CV events.
Cardiovascular disease is a leading cause of death in cancer survivors, with cancer and cardiovascular disease sharing risk factors such as ageing, tobacco use, chronic low-grade inflammation, and previous chest radiotherapy [1]. In many cancer types, the risk of cardiovascular mortality overtakes the risk of cancer mortality 5–7 years post cancer diagnosis. The early success of ICI therapy in the treatment of certain aggressive cancer types such as metastatic melanoma, has resulted in a rapid exponential increase in their use, with expansion into adjuvant and neo-adjuvant settings, and earlier use in cancer treatment algorithms (Fig. 1). Patients receiving ICI therapy are now living longer due to improved survival outcomes. Identification and awareness of the increased risk of atherosclerotic events are therefore important to understand. In this review we summarize and discuss the available literature on this topic and its implications on clinical management.

Citation

Gray, R., Manisty, C., Cheng, R., Dastidar, A., Mamas, M., & Ghosh, A. (in press). Immune checkpoint inhibitors: Unravelling atherosclerotic cardiovascular risk. Atherosclerosis, 403, Article 119147. https://doi.org/10.1016/j.atherosclerosis.2025.119147

• Journal Article Type: Article
• Acceptance Date: Feb 20, 2025
• Online Publication Date: Feb 21, 2025
• Deposit Date: Mar 28, 2025
• Journal: Atherosclerosis
• Print ISSN: 0021-9150
• Electronic ISSN: 1879-1484
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 403
• Article Number: 119147
• DOI: https://doi.org/10.1016/j.atherosclerosis.2025.119147
• Keywords: Atherosclerosis, Coronary artery disease, Immune checkpoint inhibitors, Inflammation, Cancer
• Public URL: https://keele-repository.worktribe.com/output/1110113