Abstract
In clinical trials and meta-analysis, atherosclerotic vascular events (AVEs) during treatment with immune-checkpoint inhibitors (ICIs) have been reported with low incidence. However, preclinical data suggest that these drugs can promote atherosclerosis inflammation and progression of atherosclerosis plaques, and there is now growing and convincing evidence from retrospective studies that ICIs increase the risk of atherosclerotic vascular events including arterial thrombosis, myocardial infarction and ischemic stroke. Prospective studies are needed to increase knowledge on long-term effect of ICIs or their combinations with other cardio-toxic drugs, but in the meantime a careful assessment and optimization of cardiovascular risk factors among patients treated with ICIs is advisable.
Highlights
Immune checkpoint inhibitors (ICIs) have extended survival across many tumor types and their use in cancer treatment has been increasing over time (1)
These data suggest that programmed death 1 (PD-1)/PDL1 axis has an important role in downregulating atherosclerosis by limiting antigen presenting cells (APCs)-dependent T-cell activation, and that PD1/programmed death ligand 1 (PD-L1) blockade may contribute to atherosclerosis progression in murine models through increased activation of CD4+ and CD8+ T-cells
Results from this study showed that there was a 3-fold higher risk for atherosclerotic vascular events (AVEs) after starting an ICI (HR 3.3, 95% CI 2.0–5.5; p < 0.001), in a multivariable model that included known cardiovascular risk factors
Summary
Immune checkpoint inhibitors (ICIs) have extended survival across many tumor types and their use in cancer treatment has been increasing over time (1). Approved ICIs are directed against the cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), the programmed death 1 (PD-1) and one of its ligands, the programmed death ligand 1 (PD-L1) (3). By binding their target, ICIs release the brakes that cancer cells place on the immune system, unleashing the immune cells against the tumor. ICIs are characterized by a peculiar toxicity profile consisting of immune-related adverse events (irAEs) that may potentially affect any organ or system, including the cardiovascular system (4, 5). In the present review we summarize and discuss the available literature on this topic
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