“…Dose reduction and rechallenge lead to recurrence of cardiotoxicity in 44%-90% of patients, even with prophylactic calcium blocker or nitrate treatment. 4 , 6 , 9 , 10 , 11 This illustrates the challenge of continuing potentially beneficial fluoropyrimidine treatment once cardiotoxicity has occurred.…”
“…Dose reduction and rechallenge lead to recurrence of cardiotoxicity in 44%-90% of patients, even with prophylactic calcium blocker or nitrate treatment. 4 , 6 , 9 , 10 , 11 This illustrates the challenge of continuing potentially beneficial fluoropyrimidine treatment once cardiotoxicity has occurred.…”
“…This may allow patients with GI cancer who develop cardiotoxicity (angina, vasospasm, etc) to be successfully rechallenged with 5-FU therapy. 29 Further studies identifying patients at risk for MI following 5-FU treatment are warranted. COMPETENCY IN MEDICAL KNOWLEDGE: Our study demonstrates that patients without pre-existing ischemic heart disease who developed 5-FU-associated MI had significantly higher 6-month and 1-year risk compared with matched population control subjects.…”
Background
Myocardial infarction is a cardiac adverse event associated with 5-fluorouracil (5-FU). There are limited data on the incidence, risk, and prognosis of 5-FU-associated myocardial infarction.
Objectives
The aim of this study was to examine the risk for myocardial infarction in patients with gastrointestinal (GI) cancer treated with 5-FU compared with age- and sex-matched population control subjects without cancer (1:2 ratio).
Methods
Patients with GI cancer treated with 5-FU between 2004 and 2016 were identified within the Danish National Patient Registry. Prevalent ischemic heart disease in both groups was excluded. Cumulative incidences were calculated, and multivariable regression and competing risk analyses were performed.
Results
A total of 30,870 patients were included in the final analysis, of whom 10,290 had GI cancer and were treated with 5-FU and 20,580 were population control subjects without cancer. Differences in comorbid conditions and select antianginal medications were nonsignificant (
P
> 0.05 for all). The 6-month cumulative incidence of myocardial infarction was significantly higher for 5-FU patients at 0.7% (95% CI: 0.5%-0.9%) versus 0.3% (95% CI: 0.3%-0.4%) 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% (95% CI: 0.7%-1.0%) versus 0.6% (95% CI: 0.5%-0.7%) 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; 95% CI: 1.50-2.95;
P
< 0.001) and 12 months (hazard ratio: 1.39; 95% CI: 1.05-1.84;
P
= 0.022).
Conclusions
Despite a statistically significantly higher 6- and 12-month risk for myocardial infarction among 5-FU patients compared with population control subjects, the absolute risk for myocardial infarction was low, and the clinical significance of these differences appears to be limited in the context of the significant competing risk for death in this population.
“…Through case studies it has been shown that reintroduction can be attempted in patients with suspected vasospasm after initiation of long-acting nitrates and/or calcium-channel blockers. 85 , 86 Additionally, bolus injection may be less cardiotoxic, as the vasospasm is thought to be related to accumulated metabolites rather than peak dose. The role of dihydropyrimidine dehydrogenase enzyme deficiency on cardiotoxicity is unclear.…”
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