Common Heart Failure Drugs Ease Heart Damage During Chemo

Sacubitril-valsartan, a common drug combination for heart failure, cuts the risk for cardiomyopathy after chemotherapy in patients who received anthracycline drugs by 77% in the first randomized controlled study of this approach.

The small, double-blind, placebo-controlled study, called SARAH, involved 114 patients in Brazil and was conducted over 6 months. It targeted patients undergoing chemotherapy who had evidence of the cellular damage that can lead to cardiomyopathy and were, therefore, at high risk.

Anthracycline drugs — such as doxorubicin, daunorubicin, epirubicin, and idarubicin — are used to treat many types of cancer, including leukemias, lymphomas, and breast, stomach, uterine, ovarian, bladder, and lung cancers. They are known to have toxic effects on the heart.

“There was a significant reduction in cardiotoxicity with the medication,” said investigator Marcely Bonatto, MD, from the University of São Paulo, São Paulo, Brazil. “It showed a good safety profile, with no serious adverse events or increase in treatment discontinuation,” she reported at the American Heart Association (AHA) Scientific Sessions 2024 in Chicago.

For study participants receiving sacubitril-valsartan with their chemotherapy, the rate of cardiotoxicity was only 7.1% at the end of the period of chemotherapy administration. In contrast, the rate of cardiotoxicity among patients receiving anthracycline chemotherapy and a placebo increased during the chemotherapy period, reaching 25% after 6 months. Cardiotoxicity was defined as a decrease of 15% or more in global longitudinal strain, which is associated with loss of function and clinical cardiac events.

The study participants were chosen because they had evidence of cellular damage after their chemotherapy dose, defined as an increase in high-sensitivity troponin I above the 99th percentile.

How Sacubitril-Valsartan Works 

The combination of sacubitril-valsartan, approved by the US Food and Drug Administration in 2015, contains an angiotensin receptor (valsartan) and a neprilysin inhibitor (sacubitril). The two drugs act on “two neural-hormonal mechanisms that are put in place by our body to deal with heart failure,” said Tochi M. Okwuosa, DO, director of cardio-oncology services at the Rush University Medical Center in Chicago, who was not connected with the trial.

Valsartan blocks a receptor cascade in the renin-angiotensin-aldosterone system, whereas sacubitril is beneficial to the natriuretic peptide system, she explained. The drugs are given together because valsartan blocks the negative effects of sacubitril. Five randomized controlled trials of the drugs’ effectiveness for heart failure were reported from 2014 to 2021.

Case reports, case series, and two pilot studies assessed the cardioprotective effects of sacubitril-valsartan during chemotherapy, but the pilot studies were small and did not compare the drugs with placebo or other medications, Okwuosa said. SARAH, as the first randomized controlled study of the drug combination, is an important step toward its use during chemotherapy.

Although the SARAH results are promising, more research is needed, including longer-term follow-up and trials that record outcomes, such as hospitalization for heart failure and cardiovascular and all-cause death. Cost and the availability of the drugs are also issues, she said.

Although Bonatto said she agrees that longer follow-up is needed, she disagreed with Okwuosa’s suggestion that sacubitril-valsartan be compared with valsartan alone during chemotherapy. Previous animal studies comparing sacubitril-valsartan with valsartan alone indicated that valsartan on its own is inferior for preventing cardiotoxicity, Bonatto reported, so she has no plans to compare them.