Risk of cardiovascular disease among different fluoropyrimidine-based chemotherapy regimens as adjuvant treatment for resected colorectal cancer

Background: Patients with colorectal cancer (CRC) are more likely to develop cardiovascular disease (CVD) than those without cancer. Little is known regarding their CV risk after operative chemotherapy. We aimed to compare the risk of CV disease among different fluoropyrimidine derivatives. Methods: We assembled a nationwide cohort of patients with newly diagnosed CRC between 2004 and 2015 who received fluoropyrimidine-based adjuvant chemotherapy for resected CRC by linking the Taiwan Cancer Registry (TCR), National Health Insurance Research Database (NHIRD), and Taiwan Death Registry (TDR). All eligible patients were followed from CRC diagnosis (index date) until a CV event, death, loss to follow-up, or December 31st 2018, whichever came first. CV outcomes included acute myocardial infarction (AMI), life-threatening arrhythmia (LTA), congestive heart failure (CHF), and ischemic stroke (IS). We used stabilized inverse probability of treatment weighting using propensity score (SIPTW) to balance all covariates among the three chemotherapy groups: tegafur-uracil (UFT), non-UFT, and mixed. In addition, survival analysis was conducted to examine the association between study outcomes and chemotherapy groups. Results: From 2004 to 2015, 10,615 (32.8%) patients received UFT alone, 14,511 (44.8%) patients received non-UFT, and 7,224 (22.3%) patients received mixed chemotherapy. After SIPTW, the UFT group had significantly lower all-cause mortality and cancer-related death rates than the other two chemotherapy groups. However, the UFT group had significantly higher rates of cancer death, ischemic stroke, and heart failure than those of the other two chemotherapy groups. The UFT group also had a significantly higher AMI rate than the mixed group. There was no significant difference in LTA among the three groups. Similar findings were observed in the subgroup analysis (stage II and age <70 years, stage II and age ≥70 years, stage III and age <70 years, stage III and age ≥70 years) as the overall population was observed. Conclusion: Higher heart failure and ischemic stroke rates were found in the UFT group than in the other two chemotherapy groups, especially those with stage III CRC and ≥70 years of age. Careful monitoring of this subset of patients when prescribing UFT is warranted.