Impact of statin timing on cardiovascular outcomes in gastrointestinal cancer: A real-world analysis.

535 Background: Cardiovascular disease (CVD) and cancer are two major public health challenges worldwide. CVD is the leading cause of morbidity and mortality among cancer survivors. There is extensive literature showing the vascular impact of statin therapy in the prevention of CVD. Moreover, statins reduce inflammation. However, despite this plausibility, it remains unclear whether the timing of statin initiation affects patient outcomes. We aimed to evaluate cardiovascular outcomes across three statin use patterns: initiation after diagnosis, continuation from pre-diagnosis, and discontinuation after diagnosis. Methods: Using the Blue Diamond database (2015-2024), we identified patients with non-metastatic GI cancers (esophageal, gastric, colorectal, pancreatic, hepatic). Three cohorts were analyzed: (1) New users (statin initiation post-diagnosis), (2) Continuers (statin use before and after diagnosis), and (3) Discontinuers (stopped statins post-diagnosis). A non-user cohort served as a reference. We performed 1:1 propensity score matching to adjust for confounding factors, including demographics, comorbidities, cancer type, and medications. The primary outcome was 3-year composite CV events (myocardial infarction, heart failure, stroke, or CV death). Secondary outcomes included all-cause mortality. Propensity score matching (1:1) balanced demographics, CV risk factors, cancer characteristics, and treatments. Time‐dependent Cox proportional hazard analyses were performed to assess the outcomes. Results: Among 38621 matched patients (mean age 64±10.2 years, 54% male), Continuers demonstrated the lowest 3-year CV event risk (HR 0.58, 95% CI 0.52-0.65 vs. non-users), followed by new users (HR 0.71, 95% CI 0.64-0.79). Discontinuers had a 32% higher cardiovascular risk (HR 1.32, 95% CI 1.18-1.47) compared to non-users. Continuers also showed superior 3-year survival (HR, 0.76; 95% CI, 0.69-0.84). The CV benefit was most pronounced in pancreatic (HR 0.62) and esophageal cancers (HR 0.65). Lipophilic statins showed marginally better outcomes than hydrophilic agents (HR 0.81 vs 0.85, p = 0.042). Conclusions: Continuation of pre-existing statin therapy after GI cancer diagnosis was associated with the higher cardiovascular protection, while statin discontinuation increased CV risk. Even new initiation post-diagnosis provided significant benefits, suggesting that statins may improve the quality of survivorship in GI cancer patients. These findings support the continuation of statin therapy as part of comprehensive cardio-oncologic care.