Accelerated atherosclerosis associated with immune checkpoint inhibitors: a systematic review and meta-analysis of pre-clinical studies
Abstract
BACKGROUND
Patients with cancer treated with immune checkpoint inhibitors are at increased risk of myocardial infarction and ischemic stroke. The mechanism is incompletely understood but may involve accelerated atherosclerosis due to enhanced inflammation. Pre-clinical studies may provide insight in these mechanisms.
AIM
To assess the effects of modulating co-inhibitory immune checkpoint proteins on atherosclerosis progression in animal models.
METHODS
A systematic review was performed in MEDLINE, Embase, Web of Science, and Scopus up to March 2025. Animal studies were included if the effect of modulation of programmed cell death protein 1 (PD-1), programmed death-ligand 1 (PD-L1), cytotoxic T-lymphocyte associated protein 4 (CTLA-4), and/or lymphocyte-activation gene 3 (LAG-3) on atherosclerotic plaque size was evaluated. Secondary outcomes were plaque composition and systemic inflammation. The ratios of means (RoM) across the studies were pooled in a random effects meta-analysis. Risk of bias was assessed using the SYRCLE tool, focusing on randomization, blinding, and completeness of outcome reporting.
RESULTS
Fourteen eligible studies were included. All studies used an atherosclerotic mouse model (ApoE-/-, Ldlr-/-, ApoE3∗Leiden, or AAV8-PCSK9) and either evaluated pharmacological or genetic modulation of co-inhibitory immune checkpoint proteins. Upon inhibition, atherosclerotic plaque size in the aorta was 53 % higher in exposed mice compared to control mice (RoM, 1.53;…
How strong is the evidence?
Evidence Hub reads this as a meta-analysis, done in animal, not in people. Its evidence level is 5 of 5 (Very low · case / narrative / animal / in vitro / in silico). Case reports, narrative reviews, and animal, cell or computer-model studies give the weakest evidence for human health.
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