Atherosclerotic cardiovascular events associated with immune checkpoint inhibitors in cancer patients

Abstract

Immune checkpoint inhibitors have demonstrated significant clinical benefits in many cancers, and the use of these drugs is rapidly expanding. Unfortunately, these agents can induce a wide range of immune-related adverse events through the activation of immune responses in non-target organs, including the cardiovascular system. Among cardiovascular immune-related adverse events, myocarditis is the most established and biologically plausible cardiac complication of immune checkpoint inhibitors therapy with immune-related pathophysiology. In contrast, atherosclerotic cardiovascular diseases, such as myocardial infarction and ischemic stroke, were not previously recognized as a part of the immune-related adverse event spectrum. However, there is now increasing preclinical and clinical evidence that suggests a possible correlation between immune checkpoint inhibitors therapy and atherosclerotic cardiovascular events, and cardiovascular disease is increasingly recognized as a toxicity of ICIs. Results from animal studies suggest that the blockade of the cytotoxic T-lymphocyte antigen 4 or programmed cell death protein 1 pathway plays a relevant role in promoting the progression of atherosclerotic lesions. Several clinical studies have reported an increased incidence of atherosclerotic vascular events after immune checkpoint inhibitor administration. Our findings suggest that clinicians should (i) recognize that immune checkpoint inhibitors can exacerbate atherosclerosis, (ii) consider the management of cardiovascular risk factors and (iii) perform periodic screening in patients receiving immune checkpoint inhibitors.

Keywords: atherosclerosis; cardio-oncology; cardiovascular disease; myocardial infarction; onco-cardiology.