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Association of Anthracycline With Heart Failure in Patients Treated for Breast Cancer or Lymphoma, 1985-2010
Journal article   Open access   Peer reviewed

Association of Anthracycline With Heart Failure in Patients Treated for Breast Cancer or Lymphoma, 1985-2010

Carolyn M Larsen, Mariana Garcia Arango, Harika Dasari, Maria Arciniegas Calle, Effie Adjei, Juan Rico Mesa, Christopher G Scott, Carrie A Thompson, James R Cerhan, Tufia C Haddad, …
JAMA network open, Vol.6(2), pp.e2254669-e2254669
02/01/2023
DOI: 10.1001/jamanetworkopen.2022.54669
PMCID: PMC9898820
PMID: 36735254
url
https://doi.org/10.1001/jamanetworkopen.2022.54669View
Published (Version of record) Open Access

Abstract

Anthracyclines increase the risk for congestive heart failure (CHF); however, long-term cumulative incidence and risk factors for CHF after anthracycline therapy are not well defined in population-based studies. To compare the long-term cumulative incidence of CHF in patients with breast cancer or lymphoma treated with anthracycline therapy compared with healthy controls from the same community. This retrospective population-based case-control study included data from the Rochester Epidemiology Project. Participants included residents of Olmsted County, Minnesota, diagnosed with breast cancer or lymphoma from January 1985 through December 2010 matched for age, sex, and comorbidities with healthy controls, with a final ratio of 1 case to 1.5 controls. Statistical analysis was performed between July 2017 and February 2022. Cancer treatment and CHF risk factors. The main outcome was new-onset CHF, as defined by the modified Framingham criteria. Cox proportional hazards regression was used to estimate hazard ratios (HRs) to compare the risk of CHF in participants with cancer vs controls, adjusted for age, sex, diabetes, hypertension, hyperlipidemia, coronary artery disease, obesity, and smoking history. A total of 2196 individuals were included, with 812 patients with cancer and 1384 participants without cancer. The mean (SD) age was 52.62 (14.56) years and 1704 participants (78%) were female. Median (IQR) follow-up was 8.6 (5.2-13.4) years in the case group vs 12.5 (8.7-17.5) years in the control group. Overall, patients with cancer had higher risk of CHF compared with the control cohort even after adjusting for age, sex, diabetes, hypertension, coronary artery disease, hyperlipidemia, obesity, and smoking status (HR, 2.86 [95% CI, 1.90-4.32]; P < .001). After adjusting for the same variables, CHF risk was greater for patients with cancer receiving anthracycline (HR, 3.25 [95% CI, 2.11-5.00]; P < .001) and was attenuated and lost statistical significance for patients with cancer not receiving anthracyclines (HR, 1.78 [95% CI, 0.83-3.81]; P = .14). Higher cumulative incidence for patients treated with anthracyclines vs comparator cohort was observed at 1 year (1.81% vs 0.09%), 5 years (2.91% vs 0.79%), 10 years (5.36% vs 1.74%), 15 years (7.42% vs 3.18%), and 20 years (10.75% vs 4.98%) (P < .001). There were no significant differences in risk of CHF for patients receiving anthracycline at a dose of less than 180 mg/m2 compared with those at a dose of 180 to 250 mg/m2 (HR, 0.54 [95% CI, 0.19-1.51]) or at a dose of more than 250 mg/m2 (HR, 1.23 [95% CI, 0.52-2.91]). At diagnosis, age was an independent risk factor associated with CHF (HR per 10 years, 2.77 [95% CI, 1.99-3.86]; P < .001). In this retrospective population-based case-control study, anthracyclines were associated with an increased risk of CHF early during follow-up, and the increased risk persisted over time. The cumulative incidence of CHF in patients with breast cancer or lymphoma treated with anthracyclines at 15 years was more than 2-fold that of the control group.
Anthracyclines - adverse effects Breast Neoplasms - drug therapy Breast Neoplasms - epidemiology Breast Neoplasms - pathology Case-Control Studies Child Coronary Artery Disease - complications Female Heart Failure - chemically induced Heart Failure - complications Heart Failure - epidemiology Humans Hypertension - complications Lymphoma Male Middle Aged Obesity - complications Retrospective Studies

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