February 23, 2022Open Access
View Full PaperInfluence of ejection fraction on biomarker expression and response to spironolactone in people at risk of heart failure: findings from the HOMAGE trial
Key Result
Spironolactone significantly reduced circulating levels of BNP (β = -0.36 log2, p<0.0001) and type 1 collagen, and increased LVEF by 1.1% (p=0.007) in patients at risk of heart failure.
Study Design
Type
RCT (n=527)
Structured PICO
Does spironolactone improve biomarker profiles and LVEF in patients >60 years at high risk of heart failure with LVEF ≥45%, and does baseline LVEF influence this response?
P
Population
527 patients aged >60 years at high risk of developing heart failure with LVEF ≥45%, randomized to spironolactone or standard of care for approximately 9 months.
I
Intervention
Spironolactone for ≈9 months
C
Comparator
Standard of care
O
Outcome
Circulating protein associations with LVEF and response to spironolactone (including BNP, COL1A1, and LVEF change)surrogate
In patients at high risk of heart failure with LVEF ≥45%, spironolactone reduces circulating markers of stretch and fibrosis and slightly increases LVEF, with consistent effects across the LVEF spectrum.
Main Result
Effect estimate: β = -0.36 log2
p-value: p=<0.0001
Abstract
Aims Left ventricular ejection fraction (LVEF) can provide haemodynamic information and may influence the response to spironolactone and other heart failure (HF) therapies. We aimed to study patient characteristics and circulating protein associations with LVEF, and whether LVEF influenced the response to spironolactone. Methods and results HOMAGE enrolled patients aged >60 years at high risk of developing HF with a LVEF ≥45%. Overall, 527 patients were randomized to either spironolactone or standard of care for ≈9 months, and 276 circulating proteins were measured using Olink® technology. A total of 364 patients had available LVEF determined by the Simpson's biplane method. The respective LVEF tertiles were: tertile 1: 65% ( n = 121). Patients with a LVEF >65% had smaller left ventricular chamber size and volumes, and lower natriuretic peptide levels. Compared to patients with a LVEF 65% had higher levels of circulating c‐c motif chemokine ligand‐23 and interleukin‐8, and lower levels of tissue plasminogen activator, brain natriuretic peptide (BNP), S100 calcium binding protein A12, and collagen type I alpha 1 chain (COL1A1). Spironolactone significantly reduced the circulating levels of BNP and COL1A1 without significant treatment‐by‐LVEF heterogeneity: BNP change β = −0.36 log 2 and COL1A1 change β = −0.16 log 2 ( p 0.1 for both). Spironolactone increased LVEF from baseline to month 9 by 1.1% ( p = 0.007). Conclusion Patients with higher LVEF had higher circulating levels of chemokines and inflammatory markers and lower levels of stretch, injury, and fibrosis markers. Spironolactone reduced the circulating levels of natriuretic peptides and type 1 collagen, and increased LVEF.