Bioprofiling Response to Mineralocorticoid Receptor Antagonists for the Prevention of Heart Failure
Status:
Completed
Trial end date:
2019-01-31
Target enrollment:
Participant gender:
Summary
Despite advances in care, prognosis remains poor once overt Heart Failure (HF) has developed.
Prevention is most efficient when directed toward patients at risk and when mechanistically
targeted to patients most likely to respond. An increase in myocardial and possibly vascular
collagen content (fibrosis) may be a major determinant of the transition to HF. In patients
with hypertension and diabetes, two important risk-factors for HF, changes in blood markers
of fibrosis occur before clinically overt HF develops. These markers are also related to
prognosis.
In the general population, Galectin-3 (Gal-3), a potential marker of fibrosis, is associated
with cardiovascular (CV) risk factors, and predicts development of HF. In animal models,
Gal-3 is a key mediator of aldosterone-induced CV and renal fibrosis and dysfunction.
The investigators hypothesize that the mineralocorticoid receptor antagonist (MRA),
spironolactone, may prevent HF by acting on extracellular matrix remodelling, especially in
patients with active fibrogenesis, identified by high Gal-3 levels. The benefit/risk ratio of
spironolactone might be superior in patients with a higher compared to lower plasma
concentrations of Gal-3.
Main objective is to investigate whether spironolactone can favourably alter extra-cellular
matrix remodelling, assessed by changes in the fibrosis biomarker Procollagen Type III
N-Terminal Peptide (PIIINP), in patients at increased risk of developing heart failure and
whether this effect is greater in patients with increased plasma concentrations of Gal-3.