Association of Anthracycline Use With Risk of Congestive Heart Failure Among Patients Treated for Breast Cancer or Lymphoma

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In a retrospective, population-based, case-control study reported in JAMA Network Open, Larsen et al found that patients receiving anthracyclines for breast cancer or lymphoma were at a significantly elevated risk of congestive heart failure vs noncancer controls. No significant difference in risk was identified according to cumulative anthracycline dose.

Study Details

The study used data from the Rochester Epidemiology Project on residents of Olmsted County, Minnesota, who were newly diagnosed with breast cancer or Hodgkin or non-Hodgkin lymphoma and treated with chemotherapy with or without chest or mediastinal radiotherapy between January 1985 and December 2010. A total of 812 patients with cancer were matched 1:1.5 for age, sex, and comorbidities with 1,384 controls without cancer. The main outcome measure was new-onset congestive heart failure as defined by modified Framingham criteria. 

Key Findings

Median follow-up was 8.6 years (interquartile range [IQR] = 5.2–13.4 years) in the patient group and 12.5 years (IQR = 8.7–17.5 years) in the control group.

In analysis adjusting for age, sex, diabetes, hypertension, coronary artery disease, hyperlipidemia, obesity, and smoking history, patients with cancer had a significantly elevated risk of congestive heart failure vs controls (hazard ratio [HR] = 2.86, 95% confidence interval [CI] = 1.90–4.32, P < .001). Increased risk was evident during the first year of follow-up (during which there were 12 cases of congestive heart failure) and was maintained over time after excluding congestive heart failure cases during the first year (adjusted HR = 2.41, 95% CI = 1.56–3.76, P < .001).

After adjustment for the same variables, risk of congestive heart failure among 662 patients with cancer receiving anthracycline treatment was significantly elevated vs 1,132 matched controls (HR = 3.25, 95% CI = 2.11–5.00, P < .001). A nonsignificant increase in risk was observed among 150 patients who did not receive anthracycline treatment vs 251 matched controls (HR = 1.78, 95% CI = 0.83–3.81, P = .14). The cumulative incidence of congestive heart failure for patients treated with anthracyclines vs controls was 1.81% vs 0.09% at 1 year, 2.91% vs 0.79% at 5 years, 5.36% vs 1.74% at 10 years, 7.42% vs 3.18% at 10 years, 10.75% vs 4.98% at 20 years, and 14.69% vs 9.02% at 25 years (overall P < .001).

No significant difference in risk of congestive heart failure was observed among patients receiving an anthracycline dose of < 180 mg/m2 vs those receiving a dose of 180 to 250 mg/m2 (HR = 0.54, 95% CI = 0.19–1.51) or those receiving a dose of > 250 mg/m2 (HR = 1.23, 95% CI = 0.52–2.91).

Age at diagnosis was an independent risk factor for congestive heart failure (HR per 10 years = 2.77, 95% CI = 1.99–3.86, P < .001).

The investigators concluded, “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 [twofold] that of the control group.”

Hector R. Villarraga, MD, of the Department of Cardiovascular Medicine, Mayo Clinic, Rochester, is the corresponding author for the JAMA Network Open article.

Disclosure: The study was supported by the Rochester Epidemiology Project, which is supported by the National Institute on Aging of the National Institutes of Health. For full disclosures of the study authors, visit

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