Spironolactone Does Not Reduce NTproBNP Levels in Acute Heart Failure

NT-proBNP Therapy in Heart Failure
NT-proBNP Therapy in Heart Failure
High-dose spironolactone is well-tolerated in patients with acute heart failure, but did not reduce NTproBNP levels.

NEW ORLEANS — Patients with acute heart failure (HF) did not experience reduced N-terminal pro-B type natriuretic peptide (NTproBNP) with high-dose spironolactone therapy, although high doses were well-tolerated, according to research presented at the 2016 American Heart Association Scientific Sessions.

Javed Butler, MD, MPH, MBA, of the Stony Brook School of Medicine, presented the data on behalf of the National heart Lung and Blood Institute (NHLBI) Heart Failure Clinical Research Network.

ATHENA-HF (Aldosterone Targeted NeuroHormonal CombinEd with Natriuresis TherApy in Heart Failure; ClinicalTrials.gov identifier NCT02235077) is a randomized, double-blind, placebo-controlled trial examining the safety and efficacy of spironolactone (100 mg/d) vs placebo in patients with acute HF. The researchers’ primary objective was to determine if high-dose spironolactone led to increased reductions in NTproBNP levels after 96 hours.

Between December 2014 and April 2016, 360 patients (mean age: 64.7 years; 36% female) from 22 sites were enrolled in the trial; 182 received high-dose spironolactone therapy, while 178 received usual care (132 placebo and 46 continued low-dose spironolactone).

NTproBNP median values at baseline were 3753 pg/mL (log-transformed NTproBNP: 8.23) in the placebo group and 4601 pg/mL (log-transformed NTproBNP: 8.43) in the spironolactone group. At 96 hours, they were 2080 pg/mL (log-transformed NTproBNP: 7.64) and 2672 pg/mL (log-transformed NTproBNP: 7.89). The change from baseline was -1072 pg/mL(log-transformed NTproBNP: -0.49) and -1796 pg/mL (log-transformed NTproBNP: -0.55), respectively (P =.76; .57).

After beginning treatment, the median time to discharge was 4 days in both groups. By day 30, 7 patients in the placebo arm and 5 patients in the spironolactone arm had died, and 47% and 43% in each arm, respectively, had experienced significant adverse events. Data showed no significant differences between groups in post-discharge mortality, hospitalization for HF, or number of emergency department visits.

In addition, there were no significant differences in dyspnea relief, clinical congestion, net urine output, weight loss, or clinical events. Renal function and hyperkalemia were also similar between the 2 groups.

“In ATHENA-HF, 100 mg/d spironolactone for 96 hours in [acute] HF did not achieve its primary aim of reducing NTproBNP level more than usual care alone,” Dr Butler noted in his presentation. “These data do not support the routine use of high-dose spironolactone in [acute] HF, [and] the role of high dose [mineralocorticoid receptor antagonists] targeted to patients resistant to loop diuretics needs to be further studied.”

Disclosures: Dr Tang reported receiving a research grant from the National Institutes of Health. No other financial disclosures were reported. 

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Butler J, Konstam MA, Felker M, et al. Aldosterone Targeted Neurohormonal Combined with Natriuresis Therapy in Heart Failure (ATHENA-HF) Trial. Presented at: the 2016 American Heart Association Scientific Sessions. November 12-16, 2016; New Orleans, LA.