Retrospective cohort study exploring the incidence of 5-Flurouracil associated coronary vasospasm in patients with gastrointestinal cancers

Background 5-Fluorouracil (5-FU) is an antimetabolite chemotherapy agent used to treat gastrointestinal and other solid organ malignancies. Despite its therapeutic benefits, it has known adverse effects, including severe cardiotoxicity, but most notably an association with coronary vasospasm. There are limited studies that define the incidence, risk factors, and outcomes for these patients. Purpose The objective of this project is to determine the local incidence of 5-FU-associated coronary vasospasm in patients with gastrointestinal cancers treated within our local Australian health district and explore key patient demographics, clinical characteristics and treatment-related factors that are associated with increased risk of cardiotoxicity in this cohort. Methods We conducted a retrospective analysis of all adult patients, aged 18 years and above, who were diagnosed with gastrointestinal malignancies within our local health district between 1st January 2020 to 31st December 2024 and received at least one cycle of 5-FU chemotherapy or its oral prodrug formulations. Two electronic medical records were screened manually for clinical presentations for chest pain, heart failure, acute coronary syndromes and the diagnosis of coronary vasospasm was verified with documented cardiologist opinion, along with biochemical or electrocardiographic evidence for confirmation. Results A total of 1,016 patients across four cancer centres within the district were included in the analysis. The cohort comprised of 611 males (60.1%) and 405 females (39.9%), with 41.5% patients born in Australia, 21.7% born in Asia and 16% born in Europe. Colorectal cancer constituted 65.8% of the tumour groups, while upper gastrointestinal cancers made up 34.2%. At the time of treatment, 426 patients (41.9%) had Stage III disease and 422 (41.5%) had Stage IV disease. The most frequently prescribed chemotherapy regimens were FOLFOX in 478 patients (47%) and CAPOX in 307 (30.2%) patients. Prior use of calcium channel blockers was documented in 12.7% of patients. Cardiovascular risk factors such as hypertension were documented in 42.5%, hypercholesterolemia 35.8%, diabetes in 25%, prior myocardial infarction in 7.8% and smoking history in 33.7% of patients. The incidence of 5-FU–associated coronary vasospasm was low, occurring in 5 patients (0.5%). During follow-up, the overall mortality rate was 39.4% over 5 years. The incidence of new acute coronary syndrome occurred in 2.4%, new persistent arrhythmia in 4.1% and new congestive cardiac failure in 2.4% of patients. Conclusion In this large retrospective cohort across four cancer centres, the incidence of 5-FU-associated coronary vasospasm was low (0.5%) despite a substantial burden of cardiovascular risk factors. These findings suggest that while vasospasm is an uncommon complication, ongoing cardiovascular vigilance remains important in patients receiving 5-FU–based chemotherapy.