Abstract
BACKGROUND: Immune checkpoint inhibitors (ICIs) are associated with a 3-fold risk of atherosclerotic cardiovascular disease (ASCVD). However, the biology of atherosclerosis is different among women and men, and ASCVD risk factors among women treated with an ICI are incompletely understood. This study aimed to identify factors associated with ASCVD in women following ICIs and to characterize plaque progression. METHODS: In a single-center retrospective study, clinical and cancer-related factors were compared among women treated with ICIs who did and did not experience ASCVD. Competing risk analysis estimated the effect of ICIs on cardiovascular risk. In an imaging substudy, the rate of atherosclerotic plaque progression post-treatment was compared between women and men. RESULTS: Among 1188 female patients treated with an ICI, 54 (5%) experienced an ASCVD with a median time to event of 174 days. Patients with ASCVD had a higher prevalence of prior myocardial infarction and coronary revascularization (15% versus 6%, P=0.007) and prior stroke (7% versus 2%, P=0.039). Competing risk analyses, adjusting for cardiovascular risk factors, revealed an almost 3-fold increased risk of post-ICI ASCVD in women with prior cardiovascular events (hazard ratio, 2.71 [95% CI, 1.24-5.95]; P=0.013). In an imaging study, the annual rate of plaque progression post-ICI was 6% for total and 7% for non-calcified plaque, with similar rates of progression observed in women and men. CONCLUSIONS: In female patients treated with ICIs, 5% developed an ASCVD, and a history of cardiovascular events was a risk factor. In an imaging study, plaque progressed in a short time frame after ICI therapy.