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High-dose potassium-sparing diuretic spironolactone (Aldactone) did not improve a measure of heart failure severity in acute congestion, the phase II ATHENA trial showed.
A 100-mg dose of the mineralocorticoid receptor antagonist added to usual care for 96 hours or until discharge did not improve N-terminal pro b-type natriuretic peptide (NT-proBNP) levels compared with usual care alone (log change 7.64 versus 7.98, P=0.57), , chief of the Cardiology Division of Stony Brook University in New York, and colleagues found.
Nor did any secondary endpoint show an advantage, including dyspnea relief, clinical congestion, net urine output, weight loss, or clinical events, the group reported at the .
However, because the treatment appeared to be well tolerated -- renal function did not worsen significantly in the group selected for renal sufficiency, and hyperkalemia showed a nonsignificant trend for risk -- the researchers and a discussant at a press conference for the late-breaking clinical trial suggested giving high-dose spironolactone another shot.
, of Karolinska University Hospital in Stockholm, argued that it was not the wrong pathophysiology or wrong target but might have been too low a dose, too loose inclusion criteria, or incorrect endpoints that accounted for the failure of high-dose spironolactone in the trial.
He proposed a phase III pragmatic study using doses up to 400 mg even earlier in acute decompensation in a larger population of patients with confirmed diuretic resistance.
ATHENA-HF (Aldosterone Targeted Neurohormonal Combined with Natriuresis Therapy in Heart Failure) included 360 patients at 22 sites with at least one sign and one symptom of congestion who had either not been on spironolactone or were on only a low dose at baseline. Among other criteria, patients also had to have an NT-proBNP of at least 1,000 pg/mL or BNP at least 250 pg/mL within 24 hours of randomization. Patients could not be on eplerenone (Inspra) at home or on inotropes.
Participants were randomized to receive 100 mg of spironolactone within 24 hours of their first IV diuretic dose.
For now, Butler concluded, routine use of high-dose spironolactone in acute heart failure cannot be recommended.
Disclosures
Butler disclosed financial relationships with Novartis, Janssen, ZS Pharma, Trevena, Merck, Stealth Peptide, Amgen, Bayer, CardioCell, Relypsa, and Boehringer Ingelheim.
Primary Source
American Heart Association meeting
Butler J, et al "Aldosterone Targeted NeuroHormonal CombinEd with Natriuresis TherApy in Heart Failure (ATHENA-HF) Trial" AHA 2016.