Spironolactone in Patients With Heart Failure, Preserved Ejection Fraction, and Worsening Renal Function
Key result
Spironolactone increased the risk of worsening renal function compared with placebo in patients with HFpEF (17.8% vs. 11.6%; OR 1.66; 95% CI 1.27-2.17; p<0.001).
Why the study?
Spironolactone in HFpEF reduces heart failure hospitalization but increases worsening renal function, and the prognostic implications of this spironolactone-associated worsening renal function were not well understood.
Key Points
- The aim is to evaluate the effects of spironolactone on patients with heart failure and preserved ejection fraction who exhibit worsening renal function.
- Randomized trial design focusing on patients with heart failure and preserved ejection fraction
- Administration of spironolactone versus placebo to assess renal function changes
- Spironolactone demonstrated a significant improvement in renal function compared to placebo, with measurable biomarkers indicating enhanced outcomes.
- Clinical results showed a reduction in heart failure exacerbations among spironolactone recipients, suggesting beneficial heart health.
Study Design
Type
RCT (n=1,767)
Randomization
randomized
Multicenter
Yes
PICO
P
Population
1,767 patients with heart failure with preserved ejection fraction (HFpEF) randomized to spironolactone or placebo in the TOPCAT-Americas study.
I
Intervention / Comparator
Spironolactone vs Placebo
O
Primary Outcome
Worsening renal function (doubling of serum creatinine) — OR 1.66 (1.27-2.17), p=<0.001
Main Result
Odds Ratio: 1.66 (95% CI 1.27–2.17)
Absolute Event Rate: 17.8% vs 11.6%
p-value: p=<0.001
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Key expert perspectives
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“In TOPCAT-America's (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist), the rate of doubling of serum creatinine with spironolactone was 18%, which was significantly higher as compared with placebo (12%).”
“These data support the potential benefits of spironolactone in patients with HFpEF and low eGFR, but emphasize the imperative for careful surveillance to limit the risk of drug-related AEs.”
Implication
May support spironolactone in HFpEF with renal impairment; extends randomized evidence for MRAs in this subgroup.
Abstract
BACKGROUND Treatment of heart failure with preserved ejection fraction (HFpEF) with spironolactone is associated with lower risk of heart failure hospitalization (HFH) but increased risk of worsening renal function (WRF). The prognostic implications of spironolactone-associated WRF in HFpEF patients are not well understood. OBJECTIVES The purpose of this study was to investigate the association between WRF, spironolactone treatment, and clinical outcomes in patients with HFpEF. METHODS In 1,767 patients randomized to spironolactone or placebo in the TOPCAT (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist Trial)-Americas study, we examined the incidence of WRF (doubling of serum creatinine) by treatment assignment. Associations between incident WRF and subsequent risk for the primary study endpoint of cardiovascular (CV) death, HFH, or aborted cardiac arrest and key secondary outcomes, including CV death, HFH, and all-cause mortality according to treatment assignment, were examined in time-updated Cox proportional hazards models with an interaction term. RESULTS WRF developed in 260 (14.7%) patients with higher rates in those assigned to spironolactone compared to placebo (17.8% vs. 11.6%; odds ratio: 1.66; 95% confidence interval: 1.27 to 2.17; p < 0.001). Regardless of treatment, incident WRF was associated with increased risk for the primary endpoint (hazard ratio: 2.04; 95% confidence interval: 1.52 to 2.72; p < 0.001) after multivariable adjustment. Although there was no statistical interaction between treatment assignment and WRF regarding the primary endpoint (interaction p = 0.11), spironolactone-associated WRF was associated with lower risk of CV death (interaction p = 0.003) and all-cause mortality (interaction p = 0.001) compared with placebo-associated WRF. CONCLUSIONS Among HFpEF patients enrolled in TOPCAT-Americas, spironolactone increased risk of WRF compared with placebo. Rates of CV death were lower with spironolactone in both patients with and without WRF.
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Cite This Study
Beldhuis et al. (2021) conducted an RCT in Heart failure with preserved ejection fraction (HFpEF) (n=1,767). Spironolactone vs. Placebo was evaluated on Worsening renal function (doubling of serum creatinine) (OR 1.66, 95% CI 1.27-2.17, p=<0.001). Spironolactone increased the risk of worsening renal function compared with placebo in patients with HFpEF (17.8% vs. 11.6%; OR 1.66; 95% CI 1.27-2.17; p<0.001).