Sacubitril/valsartan was associated with a lower risk cardiotoxicity compared with placebo among high-risk cancer patients being treated with anthracycline (ATN) chemotherapy agents, based on findings from the SARAH trial. The trial is the first "to demonstrate the cardioprotective potential of ARNi in high-risk patients receiving ATN therapy," said Marcely Gimenes Bonatto, MD, in presenting the findings at AHA 2024.

Researchers randomized 114 patients undergoing chemotherapy treatment with ATNs for breast cancer, lymphoma, sarcoma or leukemia in Brazil between March 2022 and August 2024 to receive either sacubitril/valsartan or placebo. Those assigned to sacubitril/valsartan started with a 24/26 mg dose twice daily, which was then titrated every two weeks until the target dose of 97/103 mg twice daily was reached. The average age of participants was 52 years, 90% of study participants self-identified as women, and 92% of participants self-identified as White adults. All participants underwent periodic clinical examinations for six months to assess heart damage and changes in function.

Among the findings, sacubitril/valsartan was associated with a 77% decrease in relative risk of further heart damage among people who already had signs of damage compared with placebo. Additionally, those in the sacubitril/valsartan group were much less likely to develop additional heart damage by the end of the 24-week intervention period.

Participants in the sacubitril/valsartan also experienced improvement in their global longitudinal strain (GLS) by an average of 2.55%, while participants in the placebo group experienced an average 6.65% decline in GLS.

"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," said Bonatto. "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."

The study had several limitations, including that all participants were at high risk for heart damage and were receiving anthracyclines for chemotherapy – 113 received doxorubicin and 1 received daunorubicin – so the findings may not apply to people with lower risk or those treated with different chemotherapy medications. Other limitations are that the study could not account for heart damage after the six-month follow-up and did not look at other factors like survival or quality of life. Additional research is also needed on more diverse patient groups.