Low- vs high-dose ARNI effects on clinical status, exercise performance and cardiac function in real-life HFrEF patients

• Published in: European journal of clinical pharmacology Vol. 78; no. 1; pp. 19 - 25
• Main Authors: Corrado, Egle, Dattilo, Giuseppe, Coppola, Giuseppe, Morabito, Claudia, Bonni, Enrico, Zappia, Luca, Novo, Giuseppina, de Gregorio, Cesare
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.01.2022; Springer Nature B.V
• Subjects: Aged; Aminobutyrates - administration & dosage; Aminobutyrates - adverse effects; Aminobutyrates - therapeutic use; Angiotensin; Angiotensin Receptor Antagonists - administration & dosage; Angiotensin Receptor Antagonists - adverse effects; Angiotensin Receptor Antagonists - therapeutic use; Biomedical and Life Sciences; Biomedicine; Biphenyl Compounds - administration & dosage; Biphenyl Compounds - adverse effects; Biphenyl Compounds - therapeutic use; Blood pressure; Blood Pressure - drug effects; Cardiomyopathy; Clinical Trial; Comorbidity; Congestive heart failure; Dose-Response Relationship, Drug; Drug Combinations; Echocardiography; Female; Heart failure; Heart Failure - drug therapy; Humans; Male; Middle Aged; Neprilysin; Patients; Pharmacology/Toxicology; Population studies; Prospective Studies; Renal function; Stroke Volume - drug effects; Valsartan - administration & dosage; Valsartan - adverse effects; Valsartan - therapeutic use; Ventricle; Ventricular Function, Left - drug effects; Walk Test; Heart failure; Sacubitril/valsartan; ARNI; 6-min walking test; Left ventricular function
• ISSN: 0031-6970; 1432-1041
• DOI: 10.1007/s00228-021-03210-0

Purpose Only a few studies are available on dose-related effects of sacubitril/valsartan (angiotensin receptor neprilysin inhibition (ARNI)) in real-life patients with heart failure and reduced ejection fraction (HFrEF). We sought to investigate clinical and functional effects in real-life HFrEF patients receiving ARNI at a different cumulative dose. Methods This was an observational study in consecutive outpatients admitted for HFrEF from October 2017 to June 2019. The PARADIGM criteria were needed for enrolment. ARNI was uptitrated according to blood pressure, drug tolerability, renal function and kaliemia. At least 10-month follow-up was required in each patient. Clinical assessment, Kansas City Cardiomyopathy Questionnaire (KCCQ) score, 6-min walk test and strain echocardiography were performed in each patient on a regular basis during the observational period. At the end of the study, patients were divided into two groups based on the median yearly dose of the ARNI medication. Results A total of 90 patients, 64 ± 11 years, 82% males, were enrolled. The cut-off dose was established in 75 mg BID, and the study population was divided into group A (≤ 75 mg), 52 patients (58%), and group B (> 75 mg), 38 patients (42%). The follow-up duration was 12 months (range 11–13). NYHA class, KCCQ score and 6MWT performance ameliorated in both groups, with a quicker time to benefit in group B. The proportion of patients walking > 350 m increased from 21 to 58% in group A ( p  < 0.001), and from 29 to 82% in group B ( p  < 0.001). A positive effect was also disclosed in the left ventricular remodelling, strain deformation and diastolic function. Conclusion One-year ARNI treatment was effective in our real-life HFrEF patient population, leading to clinical and functional improvement in both study groups, slightly greater and with a shorter time to benefit in group B.