November 11, 2018 – A new therapy could lead to improved outcomes for patients with acute decompensated heart failure.
New study results support the safety of in-hospital initiation of sacubitril-valsartan for heart failure with reduced ejection fraction (HFrEF) and may point to improved short-term clinical outcomes for patients who receive this treatment.
Acute decompensated heart failure, a clinical syndrome involving new or worsening signs and symptoms of heart failure, leads to more than 1 million hospitalizations per year in the U.S. alone. Despite the availability of promising new therapies, the standard of care — comprising of decongestion with intravenous diuretics and hemodynamic support with vasodilators and inotropes — has been largely unchanged over the past 45 years.
The PIONEER-HF trial, which sought to compare the in-hospital initiation of sacubitril-valsartan therapy with enalapril, showed no significant difference in rates of worsening renal function, hyperkalemia, symptomatic hypotension, and angioedema in heart failure patients with HFrEF.
These findings were presented Sunday at the 2018 American Heart Association Scientific Sessions in Chicago.
PIONEER-HF was a multicenter, randomized, double-blind study of the effect of sacubitril-valsartan versus enalapril on changes in NT-proBNP, as well as safety and tolerability of in-hospital initiation in HFrEF patients who have been stabilized following hospitalization for acute decompensated heart failure (ADHF). Of the 881 patients at 129 U.S. sites who were randomized, 440 were assigned to receive sacubitril-valsartan and 441 to enalapril.
In this patient population, sacubitril-valsartan therapy led to a greater and more rapid reduction in NT-proBNP than enalapril therapy. NT-proBNP is a biomarker associated with subsequent cardiovascular events. The beneficial effect of sacubitril-valsartan on NT-proBNP was accompanied by a reduction in the concentration of high-sensitivity cardiac troponin, a biomarker of myocardial injury that is associated with abnormalities in cardiac structure and function and with a worse prognosis among patients with heart failure.
An analysis of exploratory clinical outcomes showed that the in-hospital initiation of sacubitril-valsartan therapy was associated with a decrease in the rate of rehospitalization for heart failure at eight weeks.
“These study results address an important information gap in how to use sacubitril-valsartan in patients with HFrEF, showing that this is a safe strategy in these patients, and provides a marked improvement in a key biomarker,” said the DCRI’s Adam DeVore, MD, MHS, who contributed to the research.
“We also observed improved short-term clinical outcomes,” DeVore said. “Our results expand the population that could potentially benefit from sacubitril-valsartan, including patients who are hospitalized for acute decompensated heart failure, patients who have de novo heart failure, and patients not being treated with ACE inhibitors or ARBs at the time of hospitalization. Importantly, 36 percent of the U.S. patients in our trial identified as black, providing much-needed data on the use of this therapy in this population.”
The favorable effect of sacubitril–valsartan versus enalapril was evident from the in-hospital initiation of treatment and continued during the transition to home and the subsequent “vulnerable period,” when morbidity and mortality among patients with acute decompensated heart failure remain high.
“These results support a strategy of in-hospital initiation of sacubitril-valsartan for patients hospitalized with acute decompensated heart failure and have a reduced left ventricular ejection fraction,” DeVore said.
Former DCRI fellow Andrew Ambrosy, MD, also contributed to this research.
This study was funded by Novartis Pharmaceuticals.
For updated information on PIONEER-HF, check out ACC 2019: Compound improves heart failure biomarker even after hospitalization.