Sacubitril/valsartan as add-on to standard therapy in patients with heart failure: A randomized controlled trial

Abstract

BACKGROUND

Sacubitril/valsartan is a first-in-class angiotensin receptor neprilysin inhibitor (ARNI) which combines an angiotensin receptor blocker (valsartan) with sacubitril, an inhibitor of the enzyme neprilysin. By virtue of combined effect of blocking the action of angiotensin-II and inhibiting the breakdown of natriuretic peptides, ARNIs have beneficial role in heart failure (HF).

AIM

To evaluate the effect of sacubitril/valsartan on N-terminal pro-B-type natriuretic peptide (NT-pro BNP), inflammatory marker [high-sensitivity C-reactive protein (hs-CRP)], and quality of life when given as add-on to standard therapy in patients with HF.

METHODS

Sacubitril/valsartan as add-on therapy for improvement in HF study was a randomised controlled trial conducted from July 2023 to November 2024 in a public tertiary care hospital in India. Eligible patients were randomised in 1:1 ratio to either of the 2 study arms: (1) Group A (sacubitril/valsartan + standard treatment); and (2) Group B (standard treatment) for 12 weeks. Primary end point was change in NT-pro BNP levels at 12 weeks from baseline. Secondary endpoints included (1) Change in hs-CRP levels; (2) Change in World Health Organisation Quality of Life Questionnaire (WHOQOL-BREF) score; and (3) Incidence of treatment-related adverse events or worsening HF. Statistical analysis was done using Statistical Package for the Social Sciences trial version 29.0 and P < 0.05 was considered significant.

RESULTS

Out of 124 patients screened, 80 were enrolled of which 25 patients in each group were available for per-protocol analysis. At baseline, both the groups were comparable. Sacubitril/valsartan group exhibited a statistically significant greater reduction in NT-pro BNP (-35.91 ± 28.01 vs 24.68 ± 31.86; P < 0.0001) and hs-CRP (-2.87 ± 3.22 vs 0.76 ± 1.60; P < 0.0001) levels at 12 weeks compared to standard treatment group. There was also a greater improvement in quality of life with sacubitril/valsartan group (overall change in WHOQOL-BREF: 13.16 ± 8.73 in sacubitril/valsartan vs -4.12 ± 6.25 in standard treatment arm). No major adverse events were reported in two groups.

CONCLUSION

Sacubitril/valsartan demonstrated significant improvements in HF biomarkers, inflammation, and quality of life without compromising safety supporting its role as an effective addition to standard HF therapy. Further research is needed to evaluate its long-term benefits on mortality and cardiac remodeling.

Keywords: Sacubitril/valsartan; Neprilysin inhibitor; N-terminal pro-B-type natriuretic peptide; High-sensitivity C-reactive protein; World Health Organisation Quality of Life Questionnaire; Heart failure

Core Tip: This randomized clinical trial evaluated the efficacy and safety of sacubitril/valsartan, a first-in-class angiotensin receptor neprilysin inhibitor, as add-on to standard therapy compared to standard therapy alone in patients with New York Heart Association functional class II-III heart failure (HF). A total of 80 patients were enrolled out of which 25 patients in each group were available for per-protocol analysis. Baseline demographic, clinical and biochemical characteristics in both the groups were comparable. Sacubitril/valsartan demonstrated significant improvements in HF biomarkers, inflammation, and quality of life after 12 weeks without compromising safety supporting its role as an effective addition to standard HF therapy.