Fluoropyrimidine Chemotherapy and the Risk of Death and Cardiovascular Events in Patients With Gastrointestinal Cancer.

BACKGROUND

Fluoropyrimidine chemotherapy is administered first-line for many gastrointestinal cancers. However, patients with cardiovascular disease commonly receive alternative treatment due to cardiotoxicity concerns.

OBJECTIVES

This study sought to assess the risks of all-cause mortality and acute cardiovascular events with fluoropyrimidine treatment.

METHODS

We conducted an observational cohort study applying a target trial emulation framework to linked national cancer, cardiac, and hospitalization registry data from the Virtual Cardio-Oncology Research Initiative. Adults diagnosed with tumors eligible for fluoropyrimidine-based chemotherapy as first-line therapy were included. All-cause mortality and a composite of hospitalization for acute cardiovascular events (acute coronary syndrome, heart failure, cardiac arrhythmia, cardiac intervention, cardiac arrest, and cardiac death) were compared in patients treated with fluoropyrimidine-based chemotherapy vs alternative management. Adjusted, weighted pooled logistic regression models were used to estimate the 1-year risk difference (RD).

RESULTS

Among 103,110 patients (mean age 69.7 years, 59% male), the absolute risk of death at 1 year was significantly lower in fluoropyrimidine-treated patients (RD: -7.7%; 95% CI: -8.7% to -6.7%) with a small increased risk of acute cardiovascular events (RD: 0.9%; 95% CI: 0.0% to 1.9%). This was primarily due to arrhythmias (RD: 0.8%; 95% CI: 0.1% to 1.6%) and cardiac arrest (RD: 0.3%; 95% CI: 0.1% to 0.5%), with no increased risk of acute coronary syndromes including in the subgroup of patients with pre-existing coronary artery disease.

CONCLUSIONS

The markedly improved overall survival with fluoropyrimidines in patients with gastrointestinal cancer significantly outweighs the small risk of cardiac arrhythmia and arrest. Oncologists should take this into consideration for decision making to avoid undue clinical conservatism, particularly in patients with cardiovascular disease.