Sacubtril/Valsartan Lowers Cardiotoxicity Risk Linked to Chemotherapy

Marcely Bonatto, MD

Credit: American Heart Association

Sacubtril/valsartan could lower the risk of cardiotoxicity among high-risk patients with cancer undergoing treatment with anthracycline chemotherapy agents, according to late-breaking science at the American Heart Association (AHA) Scientific Sessions 2024.¹

The double-blind, randomized placebo-controlled SARAH trial examined the effect of the angiotensin receptor neprilysin inhibitor (ARNI) to prevent further heart damage among 114 adults with cancer at a single center in Brazil.

“We have identified a promising new strategy for protecting the heart during cancer treatment, with the potential to impact patient care significantly and future research in heart disease and cancer,” lead investigator Marcely Bonatto, MD, Heart Institute, University of São Paulo, said in a statement.² “Importantly, our strategy enables early identification of people at high risk for developing heart dysfunction, allowing for timely interventions to prevent further loss of heart function.”

A common class of chemotherapy medications, anthracyclines often lead to cardiomyopathy, a form of cardiotoxicity related to chemotherapy treatment. In the SARAH trial, approximately 81% of patients were being treated for breast cancer, 17% for leukemia, 2% for sarcoma, and 1% for leukemia.

According to a breakdown of the study population, patients had an average age of 52 years and 90% of participants self-identified as women and 10% self-identified as men. Moreover, 92% of adults self-identified as White, 7% as Black or mixed-race, and 1% as Asian. All were considered high-risk due to high troponin levels in the blood from pre-existing heart damage.

Each participant received clinical examinations for 6 months to determine heart damage and functional changes, including blood testing, echocardiography, and cardiac magnetic resonance imaging (MRI). SARAH was conducted from March 2022 to August 2024.

A reduction in cardiotoxicity was measured from the initiation of treatment until the end of the intervention at 24 weeks. Analysis revealed the use of sacubitril/valsartan was linked to a 77% decrease in the relative risk for further heart damage among those with pre-existing signs of damage.

Each participant started with a twice-daily dose of 24/26 mg of sacubitril/valsartan—this was titrated every 2 weeks until they reached a target dose of 97/103 mg or the highest tolerated dose without side effects. Overall, sacubitril/valsartan remained generally well-tolerated.

In comparison with the placebo cohort, the sacubitril/valsartan cohort was found less likely to develop further heart damage at the end of 24 weeks of intervention. Those in the treatment cohort saw a benefit in their global longitudinal strain (GLS) by an average of 2.55%, while the placebo cohort saw an average decline of 6.65% decline in GLS.

Bonatto addressed limitations in the study design, as all participants were at high risk for heart damage and received anthracyclines, indicating these results may not apply to lower-risk patients or those on different chemotherapy medications. Investigators called for further research using diverse patient populations, as the single-center study involved mostly White and female patients.

“Our findings highlight the importance of identifying patients with high-risk who are most likely to benefit from heart protection, and therefore, minimize unnecessary side effects and health care costs for low-risk people,” Bonatto said. “Accurately identifying which people will benefit from these strategies remains a significant challenge.”

References

1. _{Bonatto MG, Ferreira SA, Avila MS, et al. Effects of Sacubitril-Valsartan on Prevention of Cardiotoxicity in High-Risk Patients Undergoing Anthracycline Chemotherapy: A Double-Blind Randomized Placebo-Controlled Clinical Trial – The SARAH Trial. Presented at the American Heart Association (AHA) Scientific Sessions 2024. Chicago, Illinois. November 16-18, 2024.}
2. _{A common heart failure medication may help prevent heart damage related to chemotherapy. American Heart Association. November 18, 2024. Accessed November 18, 2024. https://newsroom.heart.org/news/a-common-heart-failure-medication-may-help-prevent-heart-damage-related-to-chemotherapy-6906417.}