(059) Fluoropyrimidine chemotherapy and the risk of death and cardiovascular events in patients with gastrointestinal cancer: a cohort study

Background: Fluoropyrimidine chemotherapy is used first-line for many gastrointestinal cancers. Concerns related to cardiotoxicity mean many patients may not receive optimal cancer treatment with fluoropyrimidine.

Objectives: To assess the risks of acute cardiovascular (CV) events and all-cause mortality with fluoropyrimidine treatment in patients with gastrointestinal cancers.

Methods: This is an observational cohort study using the clone-censor-weight design. We used National cancer registry data with linkage to national cardiovascular registries and Hospital Episode Statistics data from England, as part of the Virtual Cardio-Oncology Research Initiative (VICORI). We identified adult patients diagnosed with stage II-IV esophageal or gastric cancer, or stage III-IV colorectal cancer between 2014 and 2018. All patients were followed from the cancer diagnosis until outcome, death, or 1 year after the cancer diagnosis. The treatment strategies were receiving fluoropyrimidine-based chemotherapy within 8 weeks (grace period) versus no fluoropyrimidine-based treatment during follow-up. In sensitivity analyses, we extended the grace period for receiving fluoropyrimidine to 12 or 16 weeks. The primary outcomes were all-cause mortality and hospitalization for acute CV events (acute coronary syndrome, heart failure, cardiac arrhythmia, cardiac intervention, cardiac arrest, and cardiac death). Adjusted, weighted pooled logistic regression models were used to estimate 1-year risk difference (RD) and risk ratios (RR). 95% confidence intervals (CIs) were estimated using non-parametric bootstrapping.

Results: We identified 103,110 patients with a mean age of 69.7 years and 59% were male. Fluoropyrimidine treatment had a lower risk of death compared to no fluoropyrimidine treatment (RD, -7.7%; 95% CI, -8.7% to -6.7%. RR, 0.85; 95% CI, 0.83 to 0.86). There was an increased risk of CV events with fluoropyrimidine treatment (RD, 0.9%; 95% CI, 0.0% to 1.9%. RR, 1.07; 95% CI, 1.00 to 1.13). Analysis of individual CV events showed no increase in risks of acute coronary syndrome, heart failure, cardiac intervention, or cardiac death, and with an increased risk of cardiac arrhythmia (RD, 0.8%; 95% CI, 0.1% to 1.6%. RR, 1.12; 95% CI, 1.02 to 1.25) and cardiac arrest (RD, 0.3%; 95% CI, 0.1% to 0.5%. RR, 2.23; 95% CI, 1.39 to 2.78). Analyses with longer grace periods yielded consistent results.

Conclusions: The markedly improved overall survival with fluoropyrimidines in patients with gastrointestinal cancer significantly outweighs the modest increase in CV events associated with this treatment. Oncologists should take this into consideration for decision-making to avoid undue clinical conservatism.