An Analysis on Clinical Outcomes and Diuretic Requirements Following Initiation of Sacubitril/Valsartan in Patients with Chronic Heart Failure with Reduced Ejection Fraction

Abstract

Background A post-hoc analysis of the PARADIGM-HF clinical trial demonstrated treatment with sacubitril/valsartan resulted in a significant reduction in patients with worsening NYHA functional class, as compared to enalapril. Additional post-hoc analyses have revealed a reduction in intensification in outpatient diuretics, as well as a reduction in overall daily diuretic requirements, for patients treated with sacubitril/valsartan verses enalapril. Real world evidence is limited in analyzing patient experiences surrounding improvement in HF symptoms and diuretic usage. Methods This analysis was a retrospective chart review of patients consecutively prescribed sacubitril/valsartan at the Jefferson Heart Institute from January 1, 2016 until January 31, 2017. Patient clinical outcomes and diuretic requirements were analyzed for 3 months following maintenance on any dose of sacubitril/valsartan for four weeks. Chart examinations reviewed documentation for improvements in heart failure (HF) symptoms, NYHA functional class, and LVEF, as well as changes in concomitant HF medications. Safety endpoints included symptomatic hypotension and an elevation in serum creatinine and/or potassium. Results A total of 42 patients were included in the analysis. Thirty-six patients (85.7%) were titrated from their initial starting dose, although only 28 patients (66.7%) reached the targeted dose of 97/103mg twice daily. Fifty-seven percent of the patients (24/42) reported improvements in their HF-related symptoms, while 38.1% (16/42) of the patients demonstrated improvement NYHA functional classification. Thirty-six patients were concomitantly receiving loop diuretics during the initiation of sacubitril/valsartan, of whom 6 (16.7%) and 14 patients (38.9%) required discontinuation and dose reductions of loop diuretics, respectively. Twenty-two patients had a repeat ECHO after sacubitril/valsartan was initiated, fourteen of whom (63.6%) showed improvements in their LVEF. Two patients required discontinuation of therapy due to an adverse reaction; however, no other discontinuations were required from symptomatic hypotension, hyperkalemia or renal impairment. Sixteen patients (38%) experienced symptomatic hypotension, and 50% of those patients were not titrated to the target dose. Conclusion Treatment with sacubitril/valsartan resulted in an improvement in patient-reported HF symptoms, NYHA functional class and LVEF. Although the majority of patients were maintained on diuretics post initiation of sacubitril/valsartan, daily dose reductions were observed. Patients did not require discontinuation of therapy as a result of symptomatic hypotension, hyperkalemia and/or renal impairment. Despite a small sample size, this retrospective analysis serves as an example of real world experience with initiating sacubitril/valsartan in patients with chronic HFrEF.