Statin timing impact on immunotherapy-induced cardiotoxicity in gastrointestinal cancer: A real-world cohort study.

353 Background: Immune checkpoint inhibitors (ICIs) have transformed the treatment landscape of gastrointestinal (GI) malignancies but are increasingly associated with immune-related cardiovascular toxicities (irCVTs). Statins are a well-known class of lipid-lowering agents with anti-inflammatory properties, exhibiting pleiotropic anti-inflammatory and endothelial-stabilizing effects that could potentially counteract toxicity in cancer patients. In addition, the effect of the timing of concurrent statin use relative to cancer diagnosis remains poorly understood. This study investigates the association between concurrent statin use and the incidence of irCVTs among GI cancer patients receiving ICIs. Methods: We conducted a retrospective cohort study using a multi-institutional Blue Diamond database of adults diagnosed with gastrointestinal (GI) cancers (including colorectal, gastric, esophageal, hepatobiliary, and pancreatic) and treated with immune checkpoint inhibitors (ICIs) between 2016 and 2024. We performed 1:1 propensity score matching to adjust for confounding factors, including demographics, comorbidities, cancer type, and medications. Patients were categorized into three statin exposure groups: (1) Pre-ICI statin use only (discontinued at or before ICI initiation), (2) Post-ICI statin initiation, and (3) Continuous statin use (before and after ICI). The primary outcome was an incidence of irCVTs, defined as new-onset arrhythmias (e.g., atrial fibrillation, ventricular tachycardia, or heart block), and cardiomyopathy/heart failure, myocarditis, pericarditis, pericardial effusion/tamponade, diagnosed within 12 months of ICI initiation. Secondary outcomes included all-cause mortality. Outcomes were assessed with Time‐dependent Cox proportional hazard analyses. Results: Among 15,876 patients (median age 64 years; 57% male), 3,212 (20.2%) received statins: 857 with pre-ICI only, 934 with post-ICI initiation, and 1,421 with continuous statin use. The incidence of irCVTs was highest in the no statin group (6.9%), followed by pre-ICI only (6.5%), post-ICI initiation (4.1%), and continuous statin users (2.7%, p < 0.001). In multivariable Cox regression analysis, continuous statin use was associated with a significantly lower risk of irCVTs (HR, 0.49; 95% CI, 0.38–0.63) and all-cause mortality (HR, 0.74; 95% CI, 0.66–0.83) compared to nonusers. Conclusions: In this large real-world cohort of GI cancer patients treated with ICIs, continuous concurrent statin use was associated with a substantially reduced risk of immune-related cardiovascular toxicities and lower all-cause mortality. These findings support the potential role of statins as adjunctive cardioprotective agents in oncology patients undergoing immunotherapy and warrant prospective validation.