Immune checkpoint inhibitors and myocardial infarction

Abstract

Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy since their first approval in 2011. By unleashing the adaptive immune system, non-cardiac and cardiac immune-related adverse events (irAEs) are common and often pose a challenge to multidisciplinary teams treating cancer patients. A significant body of literature reports accelerated atherosclerosis - a key precursor of acute vascular events (AVEs) - with currently approved ICIs (CTLA-4, PD-1, LAG-3, and PD-L1 inhibitors), and some preclinical research also suggests increased thrombogenicity. A large meta-analysis has reported an increased incidence of AVEs, including myocardial infarction (MI) and stroke with ICIs. In addition, dyslipidemia secondary to ICI use may lead to an increase in cardiovascular (CV) events in long-term cancer survivors. Currently, there are no specific guidelines for the treatment of MI or CV risk in cancer patients with ICIs. Overall survival (≥ 6 months), thrombogenic, and bleeding risk are key determinants in choosing the appropriate acute approach and antithrombotic therapy, while other principles of MI management do not differ between cancer and non-cancer patients. Future avenues of research include lipid-lowering therapies, including PCSK9 inhibitors and statins, which may offer dual beneficial effects by improving anti-cancer efficacy and reducing CV risk. In addition, newer immune checkpoint targets may provide atheroprotection while being effective against certain cancers (e.g., CD47). Given the tremendous potential of ICIs, intensive research is warranted to reduce CV risk and the incidence of AVE, including MI, in active cancer patients and survivors.

Keywords: Acute vascular events; Atherosclerosis; Immune checkpoint inhibitors; Immunotherapy; Myocardial infarction.