Safety and tolerability of Sacubitril/Valsartan in heart failure patient with reduced ejection fraction

Abstract

Background Angiotensin receptor blocker and a neprilysin inhibitor (ARNI) has emerged as an innovative therapy for patients of heart failure with reduced ejection fraction (HFrEF). The purpose of this study was to assess the safety and tolerability of Sacubitril/Valsartan in patient with HFrEF in Pakistani population. Methods This proof-of-concept, open label non-randomized clinical trial was conducted at a tertiary care cardiac center of Karachi, Pakistan. Patients with HFrEF were prescribed with Sacubitril/Valsartan and followed for 12 weeks for the assessment of safety and tolerability. Safety measures included incidence of hypotension, renal dysfunction, hyperkalemia, and angioedema. Results Among the 120 HFrEF patients, majority were male (79.2%) with means age of 52.73 ± 12.23 years. At the end of 12 weeks, four (3.3%) patients died and eight (6.7%) dropped out of the study. In the remaining 108 patients, 80.6% (87) of the patients were tolerant to the prescribed dose. Functional class improved gradually with 75.0% (81) in class I and 24.1% (26) in class II, and only one (0.9%) patient in class III at the end of 12 weeks. Hyperkalemia remains the main safety concern with incidence rate of 21.3% (23) followed by hypotension in 19.4% (21), and renal dysfunction in 3.7% (4) of the patients. Conclusions Sacubitril/Valsartan therapy in HFrEF patients is safe and moderately tolerated among the Pakistani population. It can be used as first line of treatment for these patients. Trial registration NCT05387967. Registered 24 May 2022—Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT05387967

Effectiveness and Safety of Sacubitril/Valsartan in Heart Failure in India: A Retrospective Real-world (SAVE) Study

“…17 A marked improvement in NYHA functional class was also observed with 66.7% in class I and 26.7% in class II, and only two (6.7%) patients in class III at the end of three months; similar results were published by Khan MN et al in HFrEF patients. 1…”

“…17 A marked improvement in NYHA functional class was also observed with 66.7% in class I and 26.7% in class II, and only two (6.7%) patients in class III at the end of three months; similar results were published by Khan MN et al in HFrEF patients. 1 Sacubitril/Valsartan has been shown to be effective in a real-world scenario for HF patients with lower ejection fraction in a few recent studies. Consistent with our research, Sacubitril/Valsartan therapy was found to improve NYHA functional class, as well as reduce NT-proBNP levels and improve several hemodynamic parameters in HF patients with reduced ejection fraction in a real-world two-year follow-up study by Armentaro et al 22 In another study on non-diabetics and diabetics with HF reduced ejection fraction, a potential role of Sacubitril/Valsartan treatment was reported in HF patients with metabolic comorbidities; a persistent metabolic improvement has been noticed over the period of 12 months.…”

“…Additionally, HF significantly increases the cost burden on healthcare systems around the world. 1 Globally, 64.3 million people have been affected with HF in 2017; the highest burden of HF was noticed in Middle East, and North Africa ranging from 1133 to 1196 per 100,000 population, whereas lower burden was notified in Southeast Asia ranging from 498 to 595 per 100,000 population. With an estimated prevalence of 1.3–4.6 million people and an incidence of 0.5–1.7 per 1000 people annually, India has the highest burden of HF in Asia.…”

“…[6][7][8] Compared with already established drugs (e.g., Enalapril), ARNI usage had lowered cardiovascular deaths by 20% and all-cause mortality by 16%. 1 In HFrEF patients who were hospitalized for acute decompensated HF, the initiation of Sacubitril/Valsartan treatment led to a greater reduction in the levels of NT-proBNP versus enalapril therapy. 9 Sacubitril/Valsartan was recommended as part of optimal therapy by the European Society of Cardiology and the American Heart Association/ American College of Cardiology clinical guidelines.…”