259Higher risk of myocardial infarction in the first year following 5-fluorouracil treatment

Abstract

Abstract Abstract Background 5-fluorouracil (5-FU) is the third most commonly used chemotherapeutic agent in the treatment of solid malignancies across the world. The most common manifestation of cardiotoxicity associated with 5-FU is chest pain, presenting as atypical chest pain, angina on exertion or rest and acute coronary syndromes including myocardial infarction and in worse case even death. Nevertheless, a widespread appreciation of 5-FU related cardiotoxicity including myocardial infarction is poorly understood. Purpose This study aims to examine risk of myocardial infarction in patients treated with 5-FU compared to age- and sex-matched population controls. Methods and results Methods: Individuals treated with 5-FU between 2004 and 2014 in the Danish National Patient Register were identified and risk set matching was used to find background population controls matched on age and sex in a 1:5 ratio. Furthermore, two years follow-up time were added with total 13 years. Neither 5-FU patients nor controls had prior ischemic disease. Aalen-Johansen and Kaplan-Meier estimates were used to report the cumulative incidence of myocardial infarction and all-cause mortality, respectively. A multivariable Shared Frailty Cox regression analysis (adjusted for patient age, sex, hypertension, hypercholesterolemia, diabetes, chronic obstructive pulmonary disease, chronic kidney disease, heart failure and atrial fibrillation as well as selected anti-anginal medications including nitrates, beta- and calcium-blockers) was used to determine the association between 5-FU treatment and the one-year risk of myocardial infarction. Results A total of 9,012 5-FU patients and 45,060 controls formed the study population. Differences in comorbid conditions (diabetes, chronic obstructive pulmonary disease, chronic kidney disease, heart failure and atrial fibrillation) and selected anti-anginal medications (nitrates, beta- and calcium-blockers) were non-significant (all P>0.05). The one-year cumulative incidence of myocardial infarction is significantly higher for 5-FU patients at 0.8% versus 0.6% among population controls (Figure 1A), with a competing risk of death of 25.1% versus 1.2%. The risk diminishes beyond one year and becomes lower for 5-FU patients with time (Figure 1A), along with an increasing all-cause mortality (Figure 1B). The unadjusted and adjusted hazard ratio for the one-year risk of myocardial infarction were 1.38 [95% CI 1.07–1.78] and 1.54 [95% CI 1.19–1.99]. Conclusions Although the one-year risk of myocardial infarction is higher among 5-FU patients compared with population controls, the absolute risk is small and becomes insignificant beyond one year of follow-up.