Squint and you'll see a positive side to proteomics study HOMAGE
PHILADELPHIA -- A little positive was mixed into largely negative results with spironolactone (Aldactone) for the prevention of heart failure in a proof-of-concept trial.
Spironolactone didn't appear to favorably alter extracellular matrix remodeling among at-risk individuals with elevated NT-proBNP but not outright heart failure: serum concentrations of the fibrosis biomarker procollagen type III N-terminal peptide were no different between spironolactone and placebo groups (-0.15 vs -0.20 ng/ml, P=0.323) by the end of follow-up (up to 9 months).
Nor was spironolactone's effect more prominent in patients with increased galectin-3, which is thought to have a role in injury and vascular fibrosis, reported Faiez Zannad, MD, PhD, of Universitè de Lorraine in Nancy, France, during a late-breaking trial session at the Heart Failure Society of America meeting
However, spironolactone was linked to reduced collagen synthesis (carboxy-terminal peptide of procollagen type I -7.3 vs -0.1 ng/ml, P<0.0001) and a nonsignificant trend for better collagen degradation (carboxy-terminal telopeptide of collagen type I +0.10 vs +0.03, P=0.065).
Apart from proteomics, spironolactone decreased NT-proBNP, lowered blood pressure, and improved several echocardiographic parameters (such as reduced left ventricular mass and left atrial volume).
All this "may be indicative of an early remodeling process," the researcher said, noting that his team has more transcriptomic and proteomic data "to tease out" in the future.
"It's worth exploring spironolactone as prevention for heart failure ... to find out who benefits," Zannad suggested. He speculated that poor statistical power was behind the negative extracellular matrix remodeling finding.
HOMAGE's study population consisted of 527 patients randomized to spironolactone (25-50 mg/day) or usual care with a median follow-up of about 266 days.
The idea behind spironolactone as prevention is that, as a mineralocorticoid receptor antagonist (MRA), it can dampen a hyperactive aldosterone/mineralocorticoid receptor signaling pathway implicated in progressive heart failure.
"This is a very important study and I really think we're in a time where we need to be mindful of therapies that are effective in terms of preventing the progression in risk for heart failure," commented session panelist Kismet Rasmusson, NP, of Intermountain Heart Institute in Murray, Utah.
"Clearly, prevention is where we would like to go, and this is particularly important in HFpEF [heart failure with preserved ejection fraction] where we don't have a treatment," said fellow panelist Bertram Pitt, MD, of the University of Michigan School of Medicine in Ann Arbor.
HOMAGE was conducted at multiple sites in Europe. It included patients over age 60 and in sinus rhythm. Other eligibility criteria were ischemic heart disease accompanied by two risk factors, along with elevated NT-proBNP or BNP levels.
People with heart failure diagnoses were excluded, along with those having moderate or severe left ventricular systolic dysfunction and those taking an MRA or loop diuretic in the prior 3 months.
Patients who made it to randomization had NT-proBNP averaging around 215 ng/l in both groups. BNP, galectin-3, and high-sensitivity troponin T levels were similar as well.
By study's end, there was still no difference in New York Heart Association classifications -- the bulk of patients categorized in Class I, with about 12% in Class II.
As expected, spironolactone increased serum potassium (by a "very small" 0.23-mmol/L) and decreased eGFR (-4.58 ml/min/1.73 m2), albeit without symptoms or clinical impact, Zannad noted.
Notably, there were numerically fewer people on loop diuretics after starting spironolactone (0.8% vs 2.7%, P=0.097).
Zannad had no disclosures.
Source Reference: Zannad F "Proof of concept trial of spironolactone for the prevention of heart failure: heart omics and AGEing (HOMAGE)" HFSA 2019.
Read the original article on Medpage Today: Spironolactone for HF Prevention: Maybe?