November 10, 2018 – An analysis showed the addition of high-dose spironolactone offered no benefit in those with heightened risk for poor response to standard loop diuretics.
For clinicians treating patients with acute heart failure (AHF), managing fluid overload is a critical component of treatment in the hospital. Water retention leads to breathing problems and swelling, and standard hospital care involves removing excess fluid using diuretics.
However, many patients do not fully respond to standard diuretics and end up leaving the hospital with excess fluid. These patients are at increased risk of death or rehospitalization.
ATHENA-HF, a trial conducted by the Heart Failure Network from 2014 to 2016, assessed whether congestion would improve in AHF patients if high-dose spironolactone was added to usual therapy. The primary endpoint was a proportional change in NT-proBNP, a blood test commonly used as a marker of heart failure severity.
The trial included patients with a wide degree of risk and showed no benefit in the overall population. However, the investigators proposed that patients at highest risk of not responding to standard therapy could benefit from high-dose spironolactone.
Testing that theory, a secondary analysis of the trial focused on patients with kidney disease and other risk factors for diuretic resistance. The results of that analysis were presented today at the annual Scientific Sessions of the American Health Association in Chicago.
“Our study aimed to examine those patients who have a difficult time losing excess fluid with usual in-hospital care,” said the DCRI’s Stephen Greene, MD, who led the study. “We wanted to see if high-dose spironolactone could offer any extra benefit in the subsets of patients who do not adequately respond to typical diuretic therapy.”
“Would giving high-dose spironolactone to these high-risk patients result in them losing extra fluid, feeling better, and further lowering of NT-proBNP? Based on our study, the short answer is no.”
The researchers looked at many characteristics that put patients at increased risk of poor response to standard in-hospital care, such as kidney disease, diabetes, lower blood pressure, and high loop diuretic dose. In all of these subgroups, high-dose spironolactone did not provide extra lowering of NT-proBNP or any signal of benefit, he said.
Greene cautioned, however, that the analysis has limitations.
“Because of the design of the ATHENA-HF trial , this analysis looked at patients at risk for poor diuretic response. We weren’t able to look at the treatment effect among patients with confirmed poor diuretic response,” he said. “This is a big difference. In fact, we ended up seeing that many patients at risk for poor response actually ended up responding fairly well to standard therapy. If we studied addition of high-dose spironolactone in a population with confirmed poor urine output despite days of standard therapy, we might have seen a different result.”
Diuretic resistance is a major problem in heart failure and developing effective treatment strategies must be research priority, Greene said.
“As a field, we still need to keep searching for effective therapies to tackle this problem,” he said
Other DCRI contributors to the study included G. Michael Felker, Anna Giczewska, Hrishikesh Chakraborty, Adam DeVore, Marat Fudim, Steven McNulty, Robert Mentz, and Adrian Hernandez.