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

Purpose. Only a few studies are available on dose-related effects of Sacubitril/Valsartan (ARNI) in real-life patients with heart failure and refuced ejection fraction (HFrEF). We sought to investigate clinical and functional changes in patients receiving different ARNI 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 enrollment. 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-minute walk test and strain-echocardiography were performed in each patient on a reguar basis during the observational period. At the end of study patients were divided in two groups based on the median yearly dose of the ARNI medication. Results. 90 patients, 64±11 years, 82% males were enrolled. The cut-off dose was established in 75mg BID, and the study population divided into group A (≤75mg), 52 patients (58%) and a group B (>75mg), 38 patients (42%). Follow-up duration was 12 moths (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 >350m increased from 21% to 58% in group A (p<0.001), and from 29% to 82% in group B (p<0.001). Positive effect was also disclosed in the left ventricular remodeling, strain deformation and diastolic function. Conclusion. One-year ARNI treatment was effective in our real-life HFrEF patient population, leading to clinical and functional improvements in both study groups, but weakly greater and with a shorter time-to-benefit in group B.