Sacubitril/valsartan decreases plasma NT-proBNP in HF patients with preserved ejection fraction: JAMA

Germany: Sacubitril/valsartan significantly decreased plasma NT-proBNP levels at 12 weeks compared with standard medical therapies in patients with heart failure and left ventricular ejection factor of higher than 40%, shows a recent study. However, sacubitril/valsartan did not improve submaximal exercise capacity at 24 weeks. The study was published in the Journal of the American Medical Association (JAMA) on November 16, 2021. 

More than 50% of all patients with heart failure have preserved or mildly reduced left ventricular ejection fraction (LVEF >40%) which is related to substantial mortality and morbidity. There is not much evidence on the benefits of sacubitril/valsartan vs broader renin-angiotensin system inhibitor background therapy on 6-minute walk distance, surrogate outcome markers, and quality of life in patients with heart failure and mildly reduced or preserved LVEF of more than 40%. 

Against the above background, Burkert Pieske, Charité University Medicine, Campus Virchow Klinikum, Berlin, Germany, and colleagues aimed to the effect of sacubitril/valsartan on N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, 6-minute walk distance, and quality of life compared with background medication–based individualized comparators in patients with chronic heart failure and LVEF of more than 40% in PARALLAX Randomized Clinical Trial -- a 24-week, randomized, double-blind, parallel-group clinical trial (August 2017-October 2019).

Of 4632 patients screened at 396 centers in 32 countries, 2572 patients with heart failure, LVEF of more than 40%, elevated NT-proBNP levels, structural heart disease, and reduced quality of life were enrolled (last follow-up, October 28, 2019).

Patients were randomized in the ratio of 1:1 to receive either sacubitril/valsartan (n = 1286) or background medication–based individualized comparator (n = 1286), ie, enalapril, valsartan, or placebo stratified by prior use of a renin-angiotensin system inhibitor.

Primary endpoints were change from baseline in plasma NT-proBNP level at week 12 and in the 6-minute walk distance at week 24.

At baseline, the median NT-proBNP levels were 786 pg/mL in the sacubitril/valsartan group and 760 pg/mL in the comparator group. 

"Compared with standard medical therapies, sacubitril/valsartan resulted in a significantly greater decrease in plasma N-terminal pro–brain natriuretic peptide at 12 weeks but did not significantly improve 6-minute walk distance at 24 weeks," wrote the authors. "Further research is warranted to evaluate potential clinical benefits of sacubitril/valsartan in these patients."

Reference:

Pieske B, Wachter R, Shah SJ, et al. Effect of Sacubitril/Valsartan vs Standard Medical Therapies on Plasma NT-proBNP Concentration and Submaximal Exercise Capacity in Patients With Heart Failure andPreserved Ejection Fraction: The PARALLAX Randomized Clinical Trial. JAMA. 2021;326(19):1919–1929. doi:10.1001/jama.2021.18463