Denmark: Study on 5-FU and Myocardial Infarction

A new study has suggested that patients receiving 5-fluorouracil (5-FU) for gastrointestinal cancers are at a higher 6- and 12-month risk for myocardial infarction (MI), however, the absolute risk was low. According to the authors, this is the largest published report of 5-FU-associated MI in GI cancer patients. The study appears in the journal JACC: CardioOncology.

5-FU is a chemotherapeutic agent that is used commonly for the treatment of solid malignancies including head and neck tumors and colorectal cancer. The most common adverse event associated with its use is myocardial infarction. However, there is not much data on the incidence, risk, and prognosis of 5-FU-associated MI.

To fill this knowledge gap, Jan Walter Dhillon Shanmuganatha, Department of Cardiology, Aalborg University Hospital, Aalborg, Denmark, and colleagues aimed to examine the risk for myocardial infarction in patients treated for GI cancer with 5-FU compared with age- and sex-matched population control subjects without cancer (1:2 ratio).

For this purpose, the researchers identified GI cancer patients within the Danish National Patient Registry who were treated with 5-FU between 2004 and 2016. Prevalent ischemic heart disease in both groups was not included. Multivariable regression and competing risk analyses were performed, and cumulative incidences were calculated.

The final analysis included a total of 30,870 patients, of whom 10,290 had GI cancer and were treated with 5-FU, 20,580 were population control subjects without cancer.

Based on the study, the researchers found the following:

• Differences in comorbid conditions and select antianginal medications were nonsignificant.
• The 6-month cumulative incidence of myocardial infarction was significantly higher for 5-FU patients at 0.7% versus 0.3% in population control subjects, with a competing risk for death of 12.1% versus 0.6%.
• The 1-year cumulative incidence of myocardial infarction for 5-FU patients was 0.9% versus 0.6% among population control subjects, with a competing risk for death of 26.5% versus 1.4%.
• When accounting for competing risks, the corresponding subdistribution hazard ratios suggested an increased risk for myocardial infarction in 5-FU patients, compared with control subjects, at both 6 months (hazard ratio: 2.10) and 12 months (hazard ratio: 1.39).

"We found a higher 6- and 12-month risk for MI among 5-FU-treated patients with GI cancer versus population control subjects, although the overall absolute risk for MI was small," the authors wrote. "This could be potentially because of the competing risk for mortality in the cancer cohort." Clinical significance of these differences appears to be limited in the context of the significant competing risk for death in this population, they noted.

Reference

The study titled, "Risk for Myocardial Infarction Following 5-Fluorouracil Treatment in Patients With Gastrointestinal Cancer: A Nationwide Registry-Based Study," was published in the journal JACC: CardioOncology.

DOI: https://doi.org/10.1016/j.jaccao.2021.11.001