January 1, 2020Open Access
View Full PaperMechanistic Effects of Spironolactone on Cardiovascular and Renal Biomarkers in Heart Failure With Preserved Ejection Fraction
Key Result
Spironolactone treatment for 12 months significantly reduced levels of NT-proBNP (P=0.017) and BNP (P=0.002) compared with placebo in patients with heart failure with preserved ejection fraction.
Study Design
Type
RCT (n=247)
Blinding
Placebo-controlled
Randomization
Randomized
Multicenter
Yes
Structured PICO
Does spironolactone improve cardiovascular and renal biomarkers in patients with heart failure with preserved ejection fraction?
P
Population
247 patients with symptomatic heart failure, ejection fraction ≥45%, and elevated natriuretic peptides or prior HF hospitalization, evaluated after 12 months of treatment.
I
Intervention
Spironolactone for 12 months
C
Comparator
Placebo for 12 months
O
Outcome
Changes in biomarkers reflecting myocardial stress, myocardial injury, renal function, and systemic inflammation (BNP, NT-proBNP, hs-cTnI, hs-CRP, uric acid, urine protein-creatinine ratio) at 12 monthssurrogate
In patients with HFpEF, 12 months of spironolactone therapy significantly reduced natriuretic peptides compared to placebo, indicating potential benefits on cardiac wall stress.
Main Result
p-value: P=0.017 for NT-proBNP, P=0.002 for BNP
Abstract
Background: Spironolactone has been demonstrated to reduce heart failure (HF) hospitalization in patients with HF with preserved ejection fraction in the Americas region of the TOPCAT trial (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist Trial). We assessed effects of 12 months of treatment with spironolactone on biomarkers reflecting myocardial stress, myocardial injury, renal function, and systemic inflammation. Methods: This TOPCAT biorepository substudy evaluated 247 patients (14% of the total 1767 patients in the Americas region) with symptomatic HF, ejection fraction ≥45%, and elevated natriuretic peptides or a prior HF hospitalization. Paired blood samples at baseline and after 12 months of treatment with spironolactone or placebo were available in 204 patients. Results: At baseline, the median (interquartile range) concentration of BNP (B-type natriuretic peptide) was 124 (69–197) ng/L, NT-proBNP (N-terminal-pro-B-type natriuretic peptide) 624 (307–1312) ng/L, hs-cTnI (high sensitivity cardiac troponin I) 6.3 (3.4–13.0) ng/L, hs-CRP (high sensitivity C-reactive protein) 2.8 (1.3–6.1) mg/L, uric acid 7.2 (5.8–8.7) mg/dL, and urine protein-creatinine ratio 0.11 (0.08–0.20) mg/mg. Compared with placebo-assigned participants at 12 months, those randomized to spironolactone experienced greater reductions from baseline in levels of NT-proBNP ( P =0.017) and BNP ( P =0.002); these differences persisted after adjustment for demographics, comorbidities, estimated glomerular filtration rate, and enrollment strata. No between-group differences in changes in hs-cTnI, CRP, uric acid, or urine protein-creatinine ratio were observed. Conclusions: This TOPCAT biorepository substudy suggests potential effects on markers of cardiac wall stress or filling pressures during 12 months of treatment with spironolactone in patients with chronic HF with preserved ejection fraction. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT00094302.