The role of sacubitril/valsartan in the treatment of chronic heart failure with reduced ejection fraction in hypertensive patients with comorbidities: From clinical trials to real-world settings.

Sacubitril/valsartan, the first agent to be approved in a new class of drugs called angiotensin receptor neprilysin inhibitors (ARNIs), has been shown to reduce cardiovascular mortality and morbidity compared to enalapril in outpatient subjects with chronic heart failure (HF) and reduced left ventricular ejection fraction (HFrEF). However, there is little real-world evidence about the efficacy of ARNIs in elderly hypertensive patients with HFrEF and comorbidities. In this prospective open-label study, 108 subjects, 54 of them (mean age 78.6 ± 8.2 years, 75.0 % male), with HFrEF (29.8 ± 4.3 %) and New York Heart Association (NYHA) class II-III symptoms were assigned to receive ARNIs twice daily, according to the recommended dosage of 24/26, 49/51, 97/103 mg. Patients were gender- and age-matched with a control arm of patients with HFrEF receiving the optimal standard therapy for HF. The clinic blood pressure (BP), N-terminal pro-B-type natriuretic peptide (NT-proBNP), estimated glomerular filtration rate (eGFR), blood glucose and glycated hemoglobin (HbA1c), uric acid (UA), left ventricular ejection fraction (LVEF) and NYHA class were evaluated at a mean follow-up of 12 months. During the follow-up, the clinical outcomes, including mortality and re-hospitalization for HF, were collected. NYHA class significantly improved in the ARNI arm compared to the control (24.9 vs. 6.4 %, shifting from class III to II, and 55.4 vs. 25.2 %, from class II to I, p < 0.05 for all). A significant improvement in LVEF and eGFR levels was found in the ARNI arm compared to controls (42.4 vs. 34.2 %, 73.8 vs. 61.2 mL/min, respectively; p < 0.001 for all). NT-proBNP, clinic systolic and diastolic BP, blood glucose, HbA1c and UA values were reduced in both treatment arms, but they were lower in the ARNI arm compared controls (3107 vs. 4552 pg/mL, 112.2 vs. 120.4 and 68.8 vs. 75.6 mmHg, 108.4 vs. 112.6 mg/dL, 5.4 vs. 5.9 % and 5.9 vs. 6.4 mg/dL, respectively, p < 0.05). Mortality and re-hospitalization for HF was lower in the ARNI arm than controls (20.1 vs. 33.6 % and 27.7 vs. 46.3 % respectively; p < 0.05 for all). Gender differences were not found in either arm. No patients refused to continue the study, and no side effects to the ARNI treatment were observed. In elderly patients with HFrEF and comorbidities, ARNI treatment seems effective and safe. The improvement in LVEF and cardiac remodeling, BP, eGFR, serum glucose, UA and HbA1c could be the mechanisms by which ARNIs play their beneficial role on clinical outcomes. However, these results need to be confirmed in studies involving a greater number of subjects, and with a longer follow-up.

Mazza A ，Townsend DM ，Torin G ，Schiavon L ，Camerotto A ，Rigatelli G ，Cuppini S ，Minuz P ，Rubello D ... -  《-》

Our Experience With Sacubitril/Valsartan in Chronic Heart Failure Management - HFrEF in the Ambulatory Setting.

The prevalence of chronic heart failure (CHF) is up to 1-2% of the adult population in developed countries, rising to >10% after the age of 70. Heart failure with reduced ejection fraction (HFrEF) remains a prevalent clinical syndrome associated with significant morbidity and mortality. The aim of this study was to evaluate the clinical efficacy of sacubitril/valsartan in a group of ambulatory patients with heart failure with reduced ejection fraction (HFrEF) and its effect on the hemodynamic, metabolic, renal, and cardiac remodeling parameters. From January 2018 to May 2021, 106 patients with chronic heart failure with reduced ejection fraction (HFrEF) were prospectively enrolled. Patients treated with sacubitril/valsartan (ARNI) were compared with an arm of the same size (n = 53) and matched by age and gender who were taking a standard optimal medical therapy for HFrEF. The 106 patients completing the study were characterized by age: 69.5 ± 8.0, 64% are male gender. The mean duration of follow-up in the 2 treatment arms was 12 months. In the ARNI arm, we evaluate the hemodynamic, metabolic, renal, and cardiac remodeling parameters upon the initial evaluation and at the end of the follow-up after 12 months treatment with sacubitril/valsartan. The LVEF values increased significantly (p < 0.001) in the ARNI arm compared to the OMT arm, 42.1 % vs. 30.1%. The LVMI decreased from a baseline value of 153.1 g/m2 to 147.8 g/m2 with significant improvement only in the arm treated with ARNI. The eGFR values increased significantly (p < 0.001) in the ARNI arm compared to the OMT arm 70.1 vs. 64.9 mL/min/1.73 m2. Initiation and titration of sacubitril-valsartan was associated with a reduction in NT-pro-BNP concentration, the values of NT-pro-BNP improved significantly only in the arm treated with ARNI 3107.1 vs. 5678.2. Mortality and re-hospitalization due to HF were lower in the arm treated with ARNI compared to the control (20.3 vs. 32.4 % and 25.3 vs. 46.6 %, respectively; p < 0.05). Sacubitril/valsartan is an important advancement in the treatment of HFrEF. Sacubitril/valsartan induce "hemodynamic recovery". This study provides real-world data demonstrating incremental improvements in functional and echocardiographic outcomes in optimally treated patients with HFrEF switched to sacubitril/valsartan in ambulatory setting.

Naser N ，Kulić M ，Jatić Z 《-》

Comparison of the Efficacy and Safety of Sacubitril/Valsartan and Angiotensin-Converting Enzyme Inhibitors/Angiotensin Receptor Blockers in Patients With Reduced Ejection Fraction Combined With Moderate-to-Severe Chronic Kidney Disease.

Zhang Z ，Chen S ，Xu X ，Luo G ，Huang J ... -  《-》

Angiotensin receptor neprilysin inhibitor for patients with heart failure and reduced ejection fraction: Real-world experience from Turkey (ARNi-TR).

Ekici B ，Yaman M ，Küçük M ，Dereli S ，Yenerçağ M ，Yiğit Z ，Baş MM ，Karavelioğlu Y ，Çakmak HA ，Kıvrak T ，Özkan H ，Altın C ，Şabanoğlu C ，Demirkan B ，Ataş AE ，Kılıçaslan F ，Altay H ，Tengiz İ ，Fahri Erkan A ，Kılıçaslan B ，Olgun FE ，Durakoğlugil ME ，Alhan A ，Zoghi M ... -  《-》

Effect of Sacubitril/Valsartan vs Standard Medical Therapies on Plasma NT-proBNP Concentration and Submaximal Exercise Capacity in Patients With Heart Failure and Preserved Ejection Fraction: The PARALLAX Randomized Clinical Trial.

Pieske B ，Wachter R ，Shah SJ ，Baldridge A ，Szeczoedy P ，Ibram G ，Shi V ，Zhao Z ，Cowie MR ，PARALLAX Investigators and Committee members ... -  《-》