Anthracycline Use Linked to More than Doubling in Heart Failure Risk, Study Finds

Hector Villarraga, MD

An analysis of data from the Rochester Epidemiology Project indicates receipt of anthracyclines therapy in people with cancer was associated with a significant increase in risk of heart failure over the next 20 years.

Results of the study, which included patients from Minnesota diagnosed with breast cancer or lymphoma, suggested anthracycline therapy was associated with a 3-fold increase in risk of congestive heart failure and add to the growing recognition of cardiovascular risk associated with anthracyclines.¹

“In this retrospective population-based case-control study, anthracyclines were associated with an increased risk of [congestive heart failure] early during follow-up, and the increased risk persisted over time. The cumulative incidence of [congestive heart failure] in patients with breast cancer or lymphoma treated with anthracyclines at 15 years was more than 2-fold that of the control group,” wrote investigators.

As public health systems throughout the globe were making significant progress in turning the tide in the fight against cardiovascular disease, associations between cancer therapies and cardiotoxicity began to emerge as a new risk factor on a population level. A class of chemotherapeutic agents, anthracyclines have become the primary culprit in most studies dedicated to examining cardiotoxicity in contemporary populations. In the current study, which was led by Hector R. Villarraga, MD, and colleagues from the Mayo Clinic, investigators sought to explore associations of anthracycline use with risk of congestive heart failure using data obtained from the Rochester Epidemiology Project.

A collaboration between health care providers in Minnesota and Wisconsin, the Rochester Epidemiology Project was launched in 1966 with the intent of exploring true prevalence and outcomes of conditions in 27 counties within the 2 states.2 A retrospective case-control study, investigators designed the current research endeavor with the specific intent of assessing long-term incidence of heart failure in patients with cancer treated with anthracyclines in a population-based sample. Supported by the National Institutes of Aging and National Institutes of Health, the Rochester Epidemiology Project provided Villarraga and fellow investigators with data related to 2196 individuals for inclusion in the current study.

Limiting their analyses to residents of Olmstead County, MN newly diagnosed with and treated for breast cancer or lymphoma with chemotherapy with or without chest or mediastinal radiotherapy from January 1, 1985, through December 31, 2010, a total of 812 patients with cancer were identified via the Mayo Clinic Cancer Registry and the Rochester Epidemiology Project database for inclusion. Matching these patients based on age, calendar year, sex, and baseline comorbidities at the index date, investigators identified 1384 controls for inclusion. The mean age of people included in the study was 52.62 (SD, 14.56) years and 78% were female. Investigators noted the median follow-up was 8.6 (interquartile range [IQR], 5.2-13.4) years among the case group and 12.5 (IQR, 8.7-17.5) years for the control group.

Upon analysis, results indicated patients with cancer had a significantly greater risk of congestive heart failure when compared to those in the control cohort in analyses adjusted for age, sex, diabetes, hypertension, coronary artery disease, hyperlipidemia, obesity, and smoking status (Hazard ratio [HR], 2.86 [95% CI, 1.90-4.32]; P <.001). Further analysis using the same variables indicated this risk was attenuated and lost statistical significance for patients with cancer not receiving anthracyclines (HR, 1.78 [95% CI, 0.83-3.81]; P=.14), but appeared to increase further among those with cancer receiving anthracycline (HR, 3.25 [95% CI, 2.11-5.00]; P <.001).¹

Additional analyses suggested higher cumulative incidence for those receiving anthracyclines compared to the control cohort was observed at 1 (1.81% vs 0.09%), 5 (2.91% vs 0.79%), 10 (5.36% vs 1.74%), 15 (7.42% vs 3.18%), and 20 years (10.75% vs 4.98%) (P <.001). Investigators pointed out there were no significant differences in risk of CHF observed for patients receiving anthracyclines at a dose of less than 180 mg/m2 compared with their counterparts who received a dose of 180-250 mg/m2 (HR, 0.54 [95% CI, 0.19-1.51]) or doses exceeding 250 mg/m2 (HR, 1.23 [95% CI, 0.52-2.91]). Investigators also pointed out age at diagnosis was an indecent risk factor associated with c congestive heart failure (HR per 10 years, 2.77 [95% CI, 1.99-3.86]; P <.001).¹

In an invited commentary, Michael Fradley, MD, medical director of the Thalheimer Center for Cardio-Oncology at Penn Medicine, noted the retrospective nature of the study comes with inherent limitations, but commended the investigators for their work and the result’s addition to the growing field of cardio-oncology.

“It is clear from this study by Larsen and colleagues that there is an increased risk of both short- and long-term clinical CHF after anthracycline exposure in patients with breast cancer or lymphoma regardless of cumulative dose. These data continue to move forward the field of cardio-oncology, but they also emphasize the need for improved understanding of the pathophysiology of this disease process to facilitate better use of surveillance and treatment strategies,” Fradley wrote.³

References

1. Larsen CM, Garcia Arango M, Dasari H, et al. Association of Anthracycline With Heart Failure in Patients Treated for Breast Cancer or Lymphoma, 1985-2010. JAMA Netw Open. 2023;6(2):e2254669. doi:10.1001/jamanetworkopen.2022.54669
2. About us | Rochester Epidemiology Project. https://rochesterproject.org/our-history/. Accessed February 6, 2023.
3. Fradley MG. Heart Failure in Patients With Cancer Treated With Anthracyclines—Revisiting the Foundation of Cardio-Oncology. JAMA Netw Open. 2023;6(2):e2254677. doi:10.1001/jamanetworkopen.2022.54677