Heart failure drug may be ‘cardioprotective strategy’ for high-risk patients with cancer
Click Here to Manage Email Alerts
Key takeaways:
- New trial tested sacubitril/valsartan vs. placebo for preventing heart damage related to anthracycline chemotherapy.
- Results showed a reduction in the incidence of cardiotoxicity with this heart failure drug.
CHICAGO — Treatment with the heart failure medication sacubitril/valsartan was associated with a lower risk for chemotherapy-related heart damage among high-risk patients with cancer, according to preliminary results of the SARAH trial.
Researchers assessed the effects of the angiotensin receptor/neprilysin inhibitor sacubitril/valsartan (Entresto, Novartis) on prevention of cardiotoxicity among 114 patients undergoing chemotherapy with anthracyclines for breast cancer, lymphoma, sarcoma or leukemia, which are known to carry risk for toxic events on the heart.
“The SARAH trial is the first study to test sacubitril/valsartan as a cardioprotective strategy against anthracycline-induced cardiotoxicity, especially in high-risk patients,” Marcely Bonatto, MD, cardiologist and specialist in heart failure and heart transplantation at the Heart Institute, University of Sao Paulo, said during a press conference at the American Heart Association Scientific Sessions.
Assessing cardiotoxicity in high-risk patients
The SARAH trial enrolled adults with breast cancer (80%), lymphoma (16.7%), sarcoma (1.7%) or leukemia (0.9%) undergoing low-dose anthracycline chemotherapy.
Patients underwent screening for high-sensitivity troponin I levels after each anthracycline dose and 30 days after the final dose, and those deemed high risk based on that screening were randomly assigned to sacubitril/valsartan or placebo. The starting dose was 24/26 mg twice daily, with titration every 2 weeks until patients reached the target dose of 97/103 mg, or the maximum dose they were able to tolerate without adverse events.
The primary endpoint was cardiotoxicity, which was defined as a greater than 15% reduction in global longitudinal strain of the left ventricle, after 24 weeks.
Bonatto reported a 77% relative risk reduction in the incidence of cardiotoxicity at 24 weeks. The incidence of cardiotoxicity was 7.1% in the sacubitril/valsartan group compared with 25% in the placebo group (OR = 0.23; 95% CI, 0.07-0.75; P = .015). The difference between the groups was independent of risk factors such as age, hypertension, mean cumulative dose of anthracycline therapy and HER2 positivity, Bonatto said.
In other results, the sacubitril/valsartan group also showed improvements at 24 weeks in parameters related to heart function and size, assessed by echocardiographic and cardiac MRI, Bonatto said. Fewer patients assigned sacubitril/valsartan completed the study with cardiac dysfunction, she said.
The researchers reported a low rate of clinical events during the study, including symptomatic HF, HF hospitalization, heart transplantation, and all-cause and CV death, with no difference between the treatment groups.
The incidence of hypotension was higher in the sacubitril/valsartan group (14% vs. 1.8%), but this was not unexpected and was usually resolved by reducing the dose without the need to discontinue the medication, Bonatto said.
Sacubitril/valsartan was well tolerated by the patients in this trial, she said.
The mean age of those enrolled was 52 years and 90% were women. Ninety-two percent of participants self-identified as white. The study was conducted from March 2022 to August 2024 at a single cancer hospital in Brazil.
Insights and future directions
The SARAH researchers concluded that this research may enable identification of patients at high risk for developing heart dysfunction while undergoing chemotherapy.
“It is important to note that our strategy selected patients with evidence of cellular injury, and therefore at high risk of developing cardiotoxicity, [who] may benefit from this strategy. This helps to avoid unnecessary exposure to adverse events and cost for low-risk patients,” Bonatto said.
Further research is needed, according to the researchers and discussants of the trial.
“We need longer-term follow-up in cardio-oncology populations. The SARAH trial was just for 6 months,” Tochi M. Okwuosa, DO, FACC, FAHA, associate professor of medicine and cardiology and director of the cardio-oncology program at Rush University Medical Center, said during a discussion of the trial at the press conference.
The findings also need to be evaluated in larger populations, according to Bonnie Ky, MD, MSCE, the Founders Professor of Cardio-Oncology and director of the Thalheimer Center for Cardio-Oncology and the Penn Center for Quantitative Echocardiography at Perelman School of Medicine at University of Pennsylvania, a discussant of the trial.
“The fundamental question that cardio-oncology has been studying over the past number of decades is: How do we prevent the dose-dependent risk of anthracycline cardiotoxicity? Much of the primary focus has been on neurohormonal therapies and dexrazoxane as well as statins.
“We undoubtedly need to validate these findings in other populations. But they do generate important hypotheses that motivate studies in cardioprotection with angiotensin-neprilysin inhibitors,” Ky said.
Further, “validation [of these results] is necessary for clinical implementation,” Ky said.
Additional research, such as the PRADA II trial looking at the cardioprotective effects of sacubitril/valsartan in patients undergoing early breast cancer treatment regimens, results of which may be available in 2025, should provide further insights, according to Ky.
Collapse
Bonatto M. LBS.06. Presented at: American Heart Association Scientific Sessions; Nov. 16-18, 2024; Chicago.
Read more about
Click Here to Manage Email Alerts