Use of the common heart failure medication sacubitril/valsartan helps reduce cardiotoxicity in high-risk cancer patients undergoing anthracycline therapy, according to the results of the SARAH trial.

SARAH met its primary endpoint. After 24 weeks of treatment, patients who received sacubitril/valsartan were less likely to show a greater than 15-percent reduction in global longitudinal stain (GLS) of the left ventricle when compared with those who received placebo (7.1 percent vs 25 percent; odds ratio, 0.23, 95 percent confidence interval [CI], 0.07?0.75; p=0.015), reported lead study author Dr Marcely Bonatto from the University of Sao Paulo in Curitiba, Brazil.

For every 5.59 patients who were treated with sacubitril/valsartan, one case of cardiotoxicity could be avoided, Bonatto noted. She added that the benefit of the medication was not influenced by factors such as mean indexed cumulative dose of anthracycline, HER2 positivity, presence of hypertension, and age.

“The SARAH trial is the first to demonstrate the cardioprotective potential of an angiotensin receptor neprilysin inhibitor in high-risk patients receiving anthracycline therapy,” Bonatto said.

Improved remodelling

Results for other secondary and exploratory endpoints were consistent with that of the primary endpoint.

Over 24 weeks, GLS improved by 2.5 percent with sacubitril/valsartan and declined by 7.6 percent with placebo over 24 weeks (p<0.001). Furthermore, sacubitril/valsartan was associated with a lower likelihood of left ventricular dysfunction, as defined by LVEF of less than 50 percent on cardiac MRI (3.7 percent vs 17.0 percent; p=0.029) and GLS of greater than ?18 percent (25.0 percent vs 48.2 percent; p=0.018).

Bonatto pointed out that patients who received sacubitril/valsartan showed better parameters involved in LV remodelling on echocardiography (LVEDV with a trend toward LVEF) and cardiac MRI (LVEF and LVESV) compared with those on placebo.

Well tolerated

In terms of safety, sacubitril/valsartan was well tolerated with no serious adverse events. Clinical events were rare and occurred at similar rates in both groups, Bonatto said.

However, significantly more patients who received sacubitril/valsartan experienced hypotension (14 percent vs 1.8 percent; p=0.032) and had higher mean potassium levels (4.31 vs 4.16 mmol/L; p=0.047).

Discontinuation rates, levels of creatinine, blood pressure, troponin, NT-proBNP, and heart rate did not differ by treatment.

Promising new strategy

“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,” Bonatto said.

“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 healthcare costs for low-risk people,” she continued.

However, Bonatto acknowledged identifying people who stand to benefit most from cardioprotection during cancer treatment remains a challenge.

SARAH included 114 patients (average age 52 years, 90.4 percent female, 64 percent had at least one comorbidity) who were undergoing anthracycline chemotherapy for breast cancer (n=92), lymphoma (n=19), sarcoma (n=2), or leukaemia (n=1) at Erasto Gaertner Hospital in Curitiba, Brazil. All were considered at high risk of cardiotoxicity, defined as an increase in high-sensitivity troponin I levels above the 99th percentile after a chemotherapy session. The mean anthracycline dose was 244 mg/m².

The patients were randomly assigned to receive either sacubitril/valsartan 97/103 mg or placebo, administered twice daily for 6 months. Biomarkers, echocardiographic assessments, and cardiac magnetic resonance were performed. The baseline GLS and LVEF were ?20.1 percent and 64 percent, respectively.