Use of Sacubitril/valsartan in patients with cardio toxicity and heart failure due to chemotherapy

Abstract

Background Cancer therapy-related cardiac dysfunction (CTRCD) is a critical problem with an impact on both oncological and cardiovascular prognosis, especially when it prevents patients from receiving cancer treatment. Standard therapy for heart failure (HF) is recommended for CTRCD, but there is no well-established evidence on how sacubitril/valsartan may help cancer patients with cardiotoxicity. Objectives The aim of this trial was to study the effectiveness of sacubitril-valsartan in patients with CTRCD treated in cardio-oncology units. Methods We enrolled 635 patients with breast cancer and followed them with echocardiography and NT- proBNP. Patients who developed left ventricular dysfunction and heart failure were treated with angiotensin-converting enzyme inhibitors (ACEI) (enalapril) or angiotensin receptor blockers (ARB) (valsartan), aldosterone antagonists (eplerenone), digitalis and diuretics (furosemide), as needed. When patients remained symptomatic and met the PARADIGM-HF inclusion criteria, sacubitril/valsartan was started instead of enalapril or valsartan. We analyzed clinical, laboratory and echocardiographic variables to determine the beneficial effects of sacubitril/valsartan on left ventricular remodeling (improvement of left ventricular ejection fraction (LVEF), left ventricle internal diameter in diastole), diastolic dysfunction (E/e’ ratio), reduction in NT-proBNP levels, New York Heart Association (NHYA) class and improvement in the 6-min walk test. Also, we analyzed serum creatinine and potassium levels to determine treatmentsafety in this population. Median follow-up was 20 months. Results Twenty-eight patients developed cardiotoxicity and were treated with sacubitril/valsartan. The sacubitril/valsartan dose was 100 mg (sacubitril 49 mg/valsartan 51 mg) in 12 patients (42.85%) and 200 mg (sacubitril 97 mg/valsartan 103 mg) in 16 patients (57.15%). No deaths were reported, and one patient underwent heart transplantation. Baseline median NT-proBNP was 997.5 pg/ml (IQR 663.8 — 2380.8), which decreased to a median of 416.5 pg/ml (IQR 192.0–798.2) on follow-up with p < 0.001. Baseline NYHA functional class was III (78.6%) or IV (21.4%), and it improved to I (57.1%) or II (42.9%) on follow-up. LVEF increased with treatment from 26.7 ± 5.4% to 32.3 ± 5.5% (p < 0.001). There were also significant improvements in left ventricle internal diameter in diastole (LVIDD), diastolic function, 6-min walk test, and mitral valve regurgitation. There were no differences between basal and follow-up levels of serum creatinine or potassium. Conclusion Sacubitril/valsartan might be a promising treatment option in patients with refractory CTRCD.

Time to switch angiotensin-converting enzyme inhibitors/angiotensin receptor blockers to sacubitril/valsartan in patients with cancer therapy-related cardiac dysfunction

“…Gregorietti et al. 14 observed decreased NT-proBNP concentrations, an improved LVEF (26.7 % before vs. 32.3 % after sacubitril/valsartan), and an improved LVIDD (67.5 vs. 60 mm) in 28 patients who developed worsening cardiotoxicity and were treated with sacubitril/valsartan. However, besides these two observational studies, there are currently no data on the use of sacubitril/valsartan, except for some case series.…”

Сonsensus statement of Russian experts on the prevention, diagnosis and treatment of cardiotoxicity of anticancer therapy

“…Лечение СН, возникшей в раннем или отдаленном периоде после ХТ и/или ЛТ, должно начинаться немедленно, в соответствии с национальными рекомендациями по ее ведению [470]. В настоящее время появились данные об успешном применении при ХСН, связанной с кардиотоксичностью, валсартана/ сакубритила [471]. Поскольку нередко при СН у больных, получавших противоопухолевую терапию, имеется уширенный QRS-комплекс или блокада левой ветви пучка Гиса на ЭКГ, в ряде случаев имеется необходимость применение ресинхронизирующей терапии [472].…”

In ®Entresto we trust

“…In this issue of Cardio-Oncology Gregorietti et al [1] provide further evidence on the efficacy and safety of S/ V in the settings of CTRCD and HFrEF. The authors describe the effects of S/V in a prospective cohort of 28 patients matching the clinical cardiovascular characteristics of patients recruited in the PARADIGM-HF trial.…”

“…In this issue of Cardio-Oncology, Gregorietti et al [1] report on the clinical effects of Sacubitril/Valsartan (S/V, ®Entresto) in a small group of cancer patients, primarily women with breast cancer who developed Heart Failure with reduced Ejection Fraction (HFrEF) after treatment with anthracycline and, in few cases, with anti-ErbB2 antibodies, like trastuzumab and pertuzumab.…”

“…The study by Gregorietti et al [1] shows some obvious limitations, including the limited sample size, an insufficient characterization of patients' oncological history, the observational framework of the study design. In spite of these limitations, the study offers one more piece of evidence to improve the clinical management of patients with CTRCD.…”