medwireNews: Research has confirmed that congestive heart failure (CHF) is significantly more common in people given an anthracycline to treat breast cancer or lymphoma than among those given other types of chemotherapy, even after adjusting for confounding factors.
“Further prospective studies are required to balance the potential benefits of anthracycline vs the cardiovascular risks and to develop surveillance models and susceptibility indexes,” the investigators say in JAMA Network Open.
The case–control study identified 812 patients living in Olmsted County in Minnesota, USA, who received a diagnosis of breast cancer or lymphoma between 1985 and 2010 and were followed up for a median of 8.6 years. These individuals were matched by age, sex, comorbidity, and calendar year with 1384 individuals without cancer who were followed up for a median 12.5 years.
A diagnosis of CHF based on modified Framingham criteria was a significant 2.86 times more common among the patients with cancer than the controls after taking into consideration a raft of confounding factors including smoking history and prior diagnoses of diabetes, hypertension, coronary artery disease, hyperlipidemia, and obesity.
But further analysis showed that the increased risk of CHF after treatment for breast cancer or lymphoma was only significant for patients given an anthracycline and not those given other types of chemotherapy agents, with adjusted hazard ratios relative to the control group of 3.25 and 1.78, respectively.
The cumulative incidence of CHF in patients given anthracyclines compared with the cancer-free controls began to diverge within 1 year of follow-up (1.81 vs 0.09%) and continued for at least 25 years of follow-up (14.69 vs 9.02%).
Hector Villarraga (Mayo Clinic, Rochester, Minnesota, USA) and co-authors were unable to confirm a dose–response relationship between anthracycline use and CHF, finding no significant difference in the risks associated with cumulative doxorubicin or equivalent doses of less than 180 mg/m2, 180–250 mg/m2, or more than 250 mg/m2.
“Thus, we identified that any anthracycline use was a variable associated with increased […] risk of CHF,” they write.
In multivariable analysis, greater age at time of treatment, but not receipt of chest radiation, was a significant risk factor for CHF, and there was no protective effect with the baseline use of statins, beta-blockers, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers.
Discussing the study findings in a linked commentary, Michael Fradley (University of Pennsylvania, Philadelphia, USA) observes that the CHF diagnostic criteria used are not based on diagnostic testing and the study did not assess patients for reduced left ventricular ejection fraction, which has been “associated with higher cumulative anthracycline exposure” in previous studies.
“It is essential that we better understand the mechanism of anthracycline-associated cardiac dysfunction to offer better surveillance and management recommendations,” he emphasizes.
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JAMA Netw Open 2023; 6: e2254669
JAMA Netw Open 2023; 6: e2254677