Survival With a Cost: Increased Long-Term Coronary Artery Disease Risk After Adjuvant Fluoropyrimidine Chemotherapy in Colorectal Cancer Survivors

Background: Fluoropyrimidine-based chemotherapy, including 5-fluorouracil (5-FU) and capecitabine, is a cornerstone of adjuvant treatment in non-metastatic colorectal cancer (CRC). While acute cardiotoxicity is recognized, the long-term impact on coronary artery health remains poorly understood. This study aimed to determine whether CRC survivors treated with fluoropyrimidines exhibit a higher burden of coronary artery disease (CAD) years after therapy completion. Methods: In this prospective, single-center study, CRC survivors five to seven years post-adjuvant 5-FU/capecitabine therapy (ChemT group) were compared with age- and sex-matched cancer-free controls undergoing elective coronary angiography (n=45/group). Clinical, laboratory, echocardiographic, and invasive angiographic parameters were systematically evaluated. The primary endpoint was the presence and anatomical distribution of significant CAD. Results: Despite fewer anginal symptoms, ChemT patients had a significantly higher prevalence of CAD in the proximal left anterior descending artery (24% vs 2%, P=0.004) and proximal right coronary artery (13% vs 0%, P=0.026). Overall, 44% of ChemT patients required percutaneous coronary intervention versus 16% of controls (P=0.006), with a greater number of stents implanted in the ChemT group. Notably, the ChemT cohort also demonstrated elevated LDL cholesterol, hepatic transaminases, and abnormal hematologic indices, suggestive of long-term metabolic and vascular stress. Echocardiography revealed no significant impairment in ejection fraction but altered left ventricular geometry in the ChemT group compared to controls. Conclusions: CRC survivors treated with fluoropyrimidine-based chemotherapy exhibit a significantly elevated burden of anatomically high-risk coronary artery disease, particularly in proximal segments with poor prognostic implications. These findings highlight a silent but clinically significant cardiovascular risk in long-term cancer survivorship and support the need for proactive cardiac surveillance strategies in this population.