Angiotensin receptor neprilysin inhibitor in heart failure with reduced ejection fraction: Real-world experience from a safety perspective

Abstract

Background: Angiotensin receptor neprilysin inhibitor (ARNI) reduces morbidity and mortality in patients of heart failure with reduced ejection fraction (HFrEF). However, the use of ARNI in real-world practice is limited by safety issues, especially in acute decompensated heart failure (ADHF) patients. Methods and Results: Forty-seven hospitalized ADHF inpatients and 53 chronic compensated heart failure (CCHF) outpatients were enrolled in the study. ARNI was initiated and aimed to be up-titrated to a target dose of 97 mg of sacubitril with 103 mg of valsartan twice daily. Efficacy endpoints were New York Heart Association functional class, 6-min walk distance (6MWD), change in N-terminal pro B-type natriuretic peptide (NT-pro BNP) levels and left ventricular ejection fraction (LVEF) from baseline with follow-up at 1 month, 6 months, and 2 years. Safety endpoints were the rates of worsening serum creatinine, hyperkalemia, symptomatic hypotension, angioedema, and need for drug discontinuation. Cumulative adverse drug effect was observed in 42.6% and 13.2% patients of ADHF and CCHF groups, respectively. The most common side-effect was symptomatic hypotension that occurred in 10 (21.3%) patients of ADHF group and 3 (5.7%) patients of CCHF group. Drug discontinuation rate was 19.1% in ADHF group and 3.8% in CCHF group. Significant improvement was seen in both the groups with respect to 6 MWD, functional class, change in NT-pro BNP levels and LVEF. At 2-year follow-up, 3 (6.4%) deaths occurred in ADHF group while none was reported from CCHF group. Conclusion: ARNI results in a significant clinical, biochemical, and functional improvement in HFrEF patients but at the cost of worsening renal function and hypotension especially in ADHF setting.