Affiliation:
1. Barts Heart Centre Barts Health NHS Trust London UK
2. Institute of Cardiovascular Science University College London London UK
3. National University Health System Singapore Singapore
4. Great Ormond Street Institute of Child Health London UK
5. Barts Cancer Centre Barts Health NHS Trust London UK
6. William Harvey Research Institute Queen Mary University London London UK
7. Department of Medical Oncology Royal Free London NHS Foundation Trust London UK
Abstract
AbstractAimsFluoropyrimidine chemotherapy is important for treatment of many solid tumours but is associated with cardiotoxicity. The relationship of fluoropyrimidine‐associated cardiotoxicity (FAC) with conventional cardiovascular (CV) risk factors is poorly understood, and standard cardiovascular risk scores are not validated in this context.Methods and resultsSingle‐centre retrospective study of patients treated with fluoropyrimidine chemotherapy using electronic health records for cardiovascular risk factors (and calculation of QRISK3 score), cancer treatment, and clinical outcomes. FAC was defined by cardiovascular events during or within 3 months of fluoropyrimidine treatment, and Cox regression was used to assess associations of CV risk and cancer treatment with FAC. One thousand eight hundred ninety‐eight patients were included (45% male; median age 64 years), with median follow up 24.5 (11.5–48.3 months); 52.7% of patients were at moderate or high baseline CV risk (QRISK3 score >10%) Cardiovascular events occurred in 3.1% (59/1898)—most commonly angina (64.4%, 38/59) and atrial fibrillation (13.6%, 8/59), with 39% events during cycle one of treatment. In univariable analysis, QRISK3 score >20% was significantly associated with incident FAC (HR 2.25, 95% CI 1.11–4.93, P = 0.03). On multivariable analysis, beta‐blocker use (HR 1.04, 95% CI 1.00–1.08, P = 0.04) and higher BMI (HR 2.33, 95% CI 1.04–5.19, P = 0.04) were independently associated with incident CV events. Thirty‐two of the 59 patients with FAC were subsequently rechallenged with fluoropyrimidine chemotherapy, with repeat CV events in 6% (2/32). Incident FAC did not affect overall survival (P = 0.50).ConclusionsHigh BMI and use of beta‐blockers are associated with risk of CV events during fluoropyrimidine chemotherapy. QRISK3 score may also play a role in identifying patients at high risk of CV events during fluoropyrimidine chemotherapy. Re‐challenge with further fluoropyrimidine chemotherapy can be considered in patients following CV events during prior treatment.
Funder
British Heart Foundation
National Institute for Health and Care Research
NIHR Barts Biomedical Research Centre, Queen Mary University of London
UCLH Biomedical Research Centre