Efficacy and Safety of Angiotensin Receptor Neprilysin Inhibitor versus Angiotensin Converting Enzyme Inhibitor in Heart Failure with Reduced Ejection Fraction- A Prospective Observational Study from a Major Tertiary Care Hospital, Assam, India

Abstract

Introduction: Angiotensin Receptor Neprilysin Inhibitor (ARNI) has shown to reduce morbidity and mortality in comparison to Angiotensin Converting Enzyme Inhibitors (ACEI) inpatients of Heart Failure with Reduced Ejection Fraction (HFrEF). However, the use of ARNI in real-world practice is limited and has not been studied in North Eastern Indian population. Aim: To compare the efficacy and safety of ARNI with ACEI in the management of symptomatic chronic HFrEF in North Eastern Indian population. Materials and Methods: The prospective observational study was conducted in the Department of Cardiology at Gauhati Medical College, Guwahati, Assam, India, from April 2019 to October 2020. The study included patients with diagnosis of chronic HFrEF <40%, on ACEI therapy and who had atleast one hospitalisation for Acute Decompensated Heart Failure (ADHF) in the last 6 months. A total of 63 patients were included in this study. Three patients were lost on follow-up. Out of the 60 patients who were included in the final analysis, 30 patients each were included in two groups i.e, ARNI group and ACEI group. As perdiscretion of the treating physician, the patients were started on ARNI 50 mg twice daily which consist of Sacubitril/Valsartan (24/26 mg), along with other anti-heart failure medications, and they were compared with the patients who continued on ACEI. Uptitration was considered with the aim to double the dose till the target dose was achieved at every 2-4 weeks at the treating physician’s discretion The endpoints included the rate of repeat HF hospitalisation, mortality, renal outcomes and quality of life. All statistical analyses were performed using Statistical Package for Social Sciences (SPSS, IBM) software version 20.0. Results: The demographics and clinical characteristics were comparable between the groups. The dose of ARNI was uptitrated to a maximum of 100 mg twice daily in 11 patients. ARNI significantly reduced HF hospitalisation (36.7% vs. 66.7%; p-value=0.039) and mortality (10% vs. 20%, p-value=0.038) compared to patients with ACEI. There was a significant improvement in the KCCQ score in the ARNI group as compared to the ACEI group (p-value=0.001). Treatment with ARNI was also associated with a significant improvement in the New York Heart Association (NYHA) functional class, serum creatinine, and estimated Glomerular Filtration Rate (eGFR) and a significant reduction in N-Terminal pro B-type Natriuretic Peptide (NT-proBNP) level. Conclusion: In patients with symptomatic HFrEF, shifting to ARNI from background therapy on ACE inhibitors in comparison with continuation of ACE inhibitors appeared to be safe and superior in reducing the risk of death and of hospitalisation, when initiated on outpatient basis. ARNI could not be uptitrated in two-third of patients, yet substantial benefits are evident even at low doses in comparison to ACE inhibitor ramipril.