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.
Following were the study's key findings:
- After 12 weeks, patients in the sacubitril/valsartan group (adjusted geometric mean ratio to baseline, 0.82 pg/mL) had a significantly greater reduction in NT-proBNP levels than did those in the comparator group (adjusted geometric mean ratio to baseline, 0.98 pg/mL) with an adjusted geometric mean ratio of 0.84.
- At week 24, there was no significant between-group difference in median change from baseline in the 6-minute walk distance with an increase of 9.7 m vs 12.2 m.
- There was no significant between-group difference in the mean change in the Kansas City Cardiomyopathy Questionnaire clinical summary score (12.3 vs 11.8) or improvement in NYHA class (23.6% vs 24.0% of patients).
- The most frequent adverse events in the sacubitril/valsartan group vs the comparator group were hypotension (14.1% vs 5.5%), albuminuria (12.3% vs 7.6%), and hyperkalemia (11.6% vs 10.9%).
"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."
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