Cardiovascular safety of 5-fluorouracil and capecitabine in colorectal cancer patients: real-world evidence

BACKGROUND: Fluoropyrimidines, including 5-fluorouracil and capecitabine, are the most common chemotherapeutic agents for colorectal carcinoma. Although previous studies have suggested varying degrees of cardiotoxicity with these drugs, there is a notable lack of large-scale investigations with appropriate control groups. This study aimed to evaluate cardiovascular outcome among colorectal carcinoma patients treated with fluoropyrimidines. METHODS: A retrospective propensity score- matched cohort study was conducted in patients diagnosed with colorectal carcinoma between January 1, 1993 and December 31, 2021 at public hospitals in Hong Kong. Cardiovascular outcomes in patients prescribed fluoropyrimidines were compared with controls. Further analyses to compare 5-fluroracil and capecitabine were performed. RESULTS: A total of 51,888 colorectal carcinoma patients were identified. After 1:1 propensity score matching, 21,216 patients were included in the final analysis, with 10,608 patients in each group. 1.06% patients experienced a major adverse cardiovascular event (MACE) at 1 year. There was no significant difference in MACE risk between the two groups (HR 0.91, 95% confidence interval (95%CI): 0.70-1.18, p = 0.46). Risk of cardiovascular death was similar between the two groups (HR 1.05, 95%CI: 0.69-1.60, p = 0.82). Subgroup analysis did not demonstrate a statistically significant elevated risk of MACE during fluoropyrimidine use in high-risk patient groups. Further comparison of 5-fluorouracil and capecitabine did not reveal a difference in MACE (0.80% vs. 0.98%; HR 1.09, 95%CI: 0.64-1.85, p < 0.75). CONCLUSION: Fluoropyrimidine use in patients with colorectal carcinoma did not increase the risk of MACE, cardiovascular death, or other specific cardiovascular conditions. There was no significant difference in cardiovascular risk between 5-fluorouracil and capecitabine.