Real-world barriers to long-term ARNI therapy in HFrEF: a one-year analysis of tolerability and dose achievement

Background Sacubitril–valsartan (ARNI) has demonstrated significant benefit in reducing heart failure (HF) hospitalizations and all-cause mortality in patients with HF with reduced Ejection Fraction (HFrEF). Despite its therapeutic advantages, real- world barriers such as treatment intolerance and financial constraints may compromise long-term adherence. This study evaluated the causes of ARNI discontinuation and examined dose-titration outcomes after a 1-year follow-up in an outpatient HF management setting. Methods A total of 767 patients with HFrEF (LVEF < 40%) were included between June 2021 and June 2024, of whom 698 (91%) completed the 1-year follow-up period. The cohort had a mean age of 64 ± 10.4 years, with 64% male, and a baseline NT-proBNP concentration of 2349 ± 1522 pg/mL. The underlying etiology of HF was ischemic cardiomyopathy in 37% of patients, followed by alcoholic cardiomyopathy in 21%, tachycardia-induced cardiomyopathy in 18%, familial or hereditary forms in 13%, valvular disease in 7%, and other causes in 4%. Results After 1 year of follow-up, only 76% of patients continued ARNI therapy. The leading cause of discontinuation was hypotension (44%), followed by financial limitations (24%), renal dysfunction (12%), cough (11%), hyperkalaemia (8%), and angioedema (1%). Among patients who remained on ARNI, 25% were maintained on a low dose, 46% on an intermediate dose, and only 29% successfully reached the recommended target dose. Conclusions ARNI therapy was maintained in the majority of patients over a 1-year period, although fewer than one-third reached the target dose. Discontinuation was primarily associated with hypotension and financial difficulties, underscoring persistent real-world challenges in optimizing ARNI treatment and achieving long-term therapeutic stability in patients with HFrEF.