Efficacy and Tolerability of Very Low-Dose Sacubitril/Valsartan in heart failure with reduced ejection fraction (HFrEF) Patients

Objective: This study aims to evaluate the efficacy and tolerability of Sacubitril/valsartan commenced at a very low dose in patients with Heart Failure and Reduced Ejection Fraction (HFrEF). Methods: This was a prospective, real-world study conducted in 33 centres in Bangladesh on adult patients with symptomatic Heart failure and reduced ejection fraction (LVEF ≤ 40%) treated with a very low dose of Sacubitril/valsartan (12/13 mg) twice a day along with other standard treatment, with a 12-week follow-up. The primary endpoint was the mean change in NT-proBNP levels from baseline to week 12. Results: The study included 655 patients with a mean age of 57.98±11.98 years. The mean NT-proBNP level showed a significant decline from 2867.15 pg/mL to 938.41 pg/mL (p<0.001). Notably, over 55% of patients achieved a reduction of 50% or more NT-proBNP. Concurrently, LVEF improved significantly from 34.80±6.7% at baseline to 39.20±6.4% at 12 weeks (p<0.001). There was also a significant reduction in left ventricular end-diastolic diameter, from 60.26±6.3 mm to 57.34±6.5 mm (p<0.001). Furthermore, more than 85% of patients exhibited favourable changes in the New York Heart Association functional class at 12 weeks (p<0.001). As there was no up-titration of doses, no patients experienced symptomatic hypotension or any other serious adverse events. Conclusions: Very Low-dose sacubitril/valsartan demonstrates significant efficacy and tolerability in patients with HFrEF, as evidenced by marked reductions in NT-proBNP levels. The administration of a lower dosage may enhance patient tolerability and adherence to treatment; however, further controlled studies are necessary to confirm these findings.