No PIIINP Reduction from Spironolactone in Heart Failure Prevention Study

Faiez Zannad, MD

Results of the Heart Omics and Aging (HOMAGE) Proof of Concept Trial of Spironolactone for the Prevention of Heart Failure are offering cardiologists more insight on the impact of spironolactone treatment on cardiovascular health.

The results of the study, which were presented during the Heart Failure Society of America 2019 Scientific Sessions in Philadelphia, revealed that spironolactone did not decrease Procollagen type III N-Terminal Peptide (PIIINP) or its effect on PIIINP was modified by galectin-3 (Gal-3).

In order to determine whether spironolactone could alter extra-cellular matrix remodeling and whether the effect was greater in patients with increased plasma concentrations of Gal 03, a team of European investigators conducted a study comparing spironolactone in 25 or 50 mg per day doses to usual care.

Inclusion criteria included being over 60 years of age, having at least one cardiovascular risk factor and N-terminal-pro hormone brain natriuretic peptide (NT-proBNP) of 125 to 1000 pg/mL or BNP of 35 to 280 pg/mL. Investigators noted multiple exclusion criteria during their presentation at HFSA 2019, including recent wound healing or inflammation, preexisting clinical diagnosis of heart failure, moderate or severe left ventricular systolic ventricular dysfunction, moderate or severe valve disease, treatment with an MRA, and atrial fibrillation within one month prior to inclusion. A total of 14 were listed during the presentation.

Patients included were randomized to receive either 25 or 50 mg of spironolactone per day or usual care. The primary outcome measure of the study was change in serum concentrations of PIIINP from baseline to 9 months or final visit. Secondary outcome measures included other collagen markers, NT-proBNP, and echocardiography.

A total of 877 potential patients were screened and 317 were deemed ineligible and 34 were not randomized. Of the 527 randomized, 262 were included in the control group while 265 were randomized to receive spironolactone.

In the control group, 257 remained at month 1 and 255 remained to month 9. In the spironolactone group, 259 remained at month 1 and 251 remained until month 9.

Final analyses revealed that spironolactone did not decrease PIIINP or the impact on PIIINP was mitigated by Gal-3. Investigators noted that spironolactone improved other direct markers of collagen synthesis and degradation, decreased NT-proBNP, decreased blood pressure, and improve several echocardiography parameters including left ventricular mass, E/A ratio, left atrial volume, and left ventricular ejection fraction.

Additionally, investigators pointed out that spironolactone use increase serum K+ and decreased eGFR without symptoms or clinical impact.

This study, “Heart Omics and Aging (HOMAGE) Proof of Concept Trial of Spironolactone for the Prevention of Heart Failure,” was presented at HFSA 2019.