Benefits of Angiotensin Receptor-Neprilysin Inhibitor in Heart Failure with Reduced Ejection Fraction: A Longitudinal Study

Abstract

Introduction: Combination of Angiotensin Receptor and Neprilysin Inhibitors (ARNI) has become the mainstay drug in treatment of Heart Failure (HF) with reduced Ejection Fraction (HFrEF). However, there are very few studies to evaluate the extent and spectrum of benefit of ARNI therapy in Indian HFrEF patients. Aim: To observe the benefits of sacubitril/valsartan (ARNI) therapy on left ventricle function, parameters of cardiac remodelling, N terminal pro Brain-natriuretic peptide (NT-proBNP), rate of rehospitalisation for HF and detailed subgroup analysis in symptomatic HFrEF patients who are already receiving optimal medical therapy. Materials and Methods: This longitudinal study was conducted at Cardiology Department of Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India, from September 2018 to August 2020. Total 200 patients of HFrEF with previous echocardiographic records of past 6 months, who did not show any further improvement in left ventricle dysfunction or cardiac dimensions were included in the study. Patients were started on ARNI initially from 100 mg/day and up titrated to 400 mg/day. At each follow-up (6 weeks, 4 months, 6 months, 9 months and 1 year) clinical examination, New York Heart Association (NYHA) functional class, 2D Echocardiography and NT-ProBNP were done. Echocardiographic parameters of Cardiac Reverse Remodelling (CRR) i.e., Left Ventricular Ejection Fraction (LVEF), Left Ventricular End Diastolic Diameter (LVEDD), Left Ventricle End-Systolic Diameter (LVESD) were recorded at each follow-up. All categorical variables were shown in the form of frequency, mean with standard deviation and percentage. Intergroup comparison between different time periods was done by one-way Analysis of Variance (ANOVA) and paired t-test. A p-value <0.05 was considered statistically significant. Results: Mean age of study population was 58.61±11.95 years, of whom 104 (59.77%) were males, and 70 (40.22%) were females. Mean LVEF increased from 30.42% at baseline to 45.98%, after 1 year (p-value <0.05). There was reduction in mean LVEDD of 4.5 mm (p<0.05) and LVESD of 3.86 mm (p-value <0.05) at 1 year. These benefits of CRR were observed in all the subgroups of study population (including diabetics, hypertensive, tobacco users, age, gender). Reduction in NT-ProBNP from 1097.65±769.7 pg/mL at baseline to 127.28 pg/mL after 1 year with mean reduction of 970.37±731.33 pg/mL (p-value <0.05). Rate of rehospitalisation for HF was 13.2% (N=23). A positive although weak correlation was seen between change in NT-ProBNP level and change in LVEF, LVEDD, LVESD as per spearman’s rank correlation coefficient. Conclusion: ARNI was well tolerated in this Indian population as 72% achieved maximum dose of 400 mg. There was significant improvement in LV systolic function and cardiac dimensions and benefits extended to different subgroups of HFrEF patients along with positive although weak correlation between fall in NT-ProBNP level and improvement in LV function and cardiac dimensions over and above optimal medical therapy.