No Added Value to High-Dose Spironolactone in Acute Heart Failure: ATHENA-HF

Larry Hand

November 30, 2016

NEW ORLEANS, LA — Clinical-trial results do not support routine use of high-dose spironolactone for treatment in hospitalized patients with acute heart failure, according to results presented this month at the American Heart Association (AHA) 2016 Scientific Sessions[1].

"What we basically found was that neither the primary or any of the secondary end points improved in our trial with this strategy," Dr Javed Butler (Stony Brook University, NY), who presented the results, told heartwire from Medscape in an interview.

Butler and colleagues conducted the Aldosterone Targeted Neurohormonal Combined With Natriuresis Therapy—Heart Failure (ATHENA-HF) trial between December 2014 and April 2016. A total of 360 patients were enrolled at 22 sites.

They randomized 182 patients to high-dose spironolactone (100 mg) for 96 hours or to discharge and 178 to usual care, with 132 of those randomized to placebo and 46 continuing low-dose spironolactone. Mean patient age was 65, and 64% were males.

About half had atrial fibrillation, and more than 80% had hypertension. About 40% had diabetes, just under a third had MI, and just under a third had chronic kidney disease. Estimated glomerular filtration rate was a mean of 55 mL/minute per 1.73 m2 for placebo patients and 58 mL/minute per 1.73 m2 for spironolactone patients at baseline.

The primary end point was reduction in N-terminal pro-B-type natriuretic peptide (NT-proBNP). The researchers found that patients on placebo experienced a change from baseline log NT-proBNP of 8.23 to 7.64 after 96 hours, while patients on spironolactone experienced a change from 8.43 at baseline to 7.89 after 96 hours (P=0.57).

Secondary end points, including dyspnea Likert Score, also did not change significantly.

"It was a totally neutral trial," Butler said. "One thing one can say is that this intervention doesn't work out. The other interpretation is that at least in other places where aldosterone is modulated, like cirrhosis, they used 200-400 mg spironolactone. Maybe we should use higher doses.

"My personal interpretation is that because of the fear of using high-dose spironolactone and risk for hyperkalemia, it was felt that the patient should have relatively preserved renal function," he added. "We found no hyperkalemia at all.

Dr Lars H Lund (Karolinska Institutet, Stockholm, Sweden), discussant at the presentation, said the neurohormonal target has been used successfully in chronic heart failure but effects are still unknown in acute heart failure. He questioned whether diuretic resistance is a risk factor or a risk marker in acute heart failure.

He said one reason the trial turned out neutral is it may have involved the wrong patients, patients with modest fluid retention and no evidence for diuretic resistance. Another reason could have been the wrong primary end point.

"Surrogate end points such as NT-proBNP have repeatedly proven unreliable," he said. "High-dose MRA [therapy] should be further explored in acute heart failure."

The National Heart, Lung, and Blood Institute (NHLBI) supported this research. Butler received funding from the NHLBI.

Follow Larry Hand on Twitter: @LarryHand16. For more from, follow us on Twitter and Facebook.


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.