In-hospital sacubitril- valsartan reduces NT-proBNP in patients with ADHF
The administration of sacubitril-valsartan, an angiotensin receptor-neprilysin inhibitor, during hospitalization significantly reduces the N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels among patients with acute decompensated heart failure (ADHF) and reduced ejection fraction compared with enalapril, according to the PIONEER-HF* trial.
“The favourable effect of sacubitril-valsartan, as compared with enalapril, was evident from the in-hospital initiation of treatment and continued to be present during the transition to home and throughout the subsequent ‘vulnerable period’, during which morbidity and mortality among patients with ADHF remains high,” according to study lead author Dr Eric Velazquez from the Section of Cardiovascular Medicine, Department of Internal Medicine at Yale University School of Medicine in New Haven, Connecticut, US. [N Engl J Med 2018;doi:10.1056/NEJMoa1812851]
This multicentre, double-blind, active-controlled trial enrolled 881 patients hospitalized for ADHF with reduced ejection fraction (median age 61 years, 28 percent female, median NT-proBNP 4,812 pg/mL) from 129 centres in the US. Once the patients were haemodynamically stable (defined as SBP** of at least 100 mm Hg), they were randomized to receive either oral sacubitril 24 mg with valsartan 26 mg or enalapril 2.5 mg [for SBP 100 to <120 mm Hg]/sacubitril 49 mg with valsartan 51 mg or enalapril 5 mg [for SBP ≥120 mm Hg] twice daily for an 8-week treatment period. [AHA 2018, abstract LBS.05-19328]
At 8-week visit, 55.2 percent and 60.8 percent of patients in the sacubitril–valsartan and enalapril groups were given the target treatment dose (sacubitril 97 mg with valsartan 103 mg and enalapril 10 mg twice daily, respectively).
Patients in the sacubitril-valsartan group had a significantly greater reduction in NT-proBNP levels from baseline compared with the enalapril group at 8 weeks (change from baseline, -46.7 percent vs -25.3 percent, ratio of change, 0.71, 95 percent confidence interval [CI], 0.63–0.81; p<0.001).
In addition, a greater reduction in the NT-proBNP level was already evident at week 1 among patients treated with sacubitril-valsartan compared with enalapril (ratio of change, 0.76, 95 percent CI, 0.69–0.85).
The rates of serious composite clinical endpoint of death, rehospitalization due to heart failure, implantation of left ventricular assist device, or cardiac transplant listing were significantly lower among patients on sacubitril-valsartan than those on enalapril at 8 weeks (9.3 percent vs 16.8 percent, hazard ratio, 0.54; p=0.001).
With regards to safety, both the sacubitril-valsartan and enalapril groups showed no significant difference on the incidence rates of worsening renal function, hyperkalaemia, and symptomatic hypotension. “[This finding] is reassuring, especially among patients with ADHF, who are at a high risk for haemodynamic instability,” Velasquez said.
Of note, lower angioedema events were observed in patients treated with sacubitril-valsartan than with enalapril (one vs six events).
“These results support the in-hospital initiation of sacubitril-valsartan in stabilized patients with ADHF and reduced ejection fraction, irrespective of prior ACEi/ARB use, or prior HF diagnosis,” said Velasquez.
“[Furthermore,] the results of the PIONEER-HF trial extend the evidence base regarding the use of sacubitril-valsartan to populations for which there had been limited or no data, including patients who are hospitalized for ADHF, patients who have new heart failure, patients who have not been exposed to high doses of guideline-directed medications for heart failure, and patients who are not receiving conventional renin-angiotensin system inhibitors,” Velasquez added.
“There has been a need for a study like PIONEER in the care of heart failure,” said invited discussant, Dr Larry Allen from the University of Colorado School of Medicine in Denver, US. “In a post-PIONEER world, I think one of the great things about this study is ‘KIS’ (keep it simple), we now have a simple or simpler algorithm for inpatient and subsequent outpatient HFrEF*** management. It’s easier for us to start with the therapy of what we want them to be on and it’s easier for patients to start with the therapy that they’re going to take. Finally, most importantly, this reinforces the importance and safety of aggressive guideline-directed medical therapy for most patients from the beginning.”
*PIONEER-HF: Comparison of sacubitril/valsartan versus enalapril on effect on NT-proBNP in patients stabilized from an acute heart failure episode
**SBP: Systolic blood pressure*** HFrEF: Heart failure with reduced ejection fraction