Key result
Spironolactone reduces a composite of outpatient diuretic intensification, HF hospitalization, or CV death by ~26%.
Why the study?
Outpatient treatment for worsening heart failure is usually not incorporated in the main outcomes of HF trials, despite frequent outpatient worsening episodes in HFpEF.
Does spironolactone reduce outpatient diuretic intensification and subsequent cardiovascular events in patients with HFpEF?
RCT (n=1,767)
Yes
Does spironolactone reduce outpatient diuretic intensification and subsequent cardiovascular events in patients with HFpEF?
In patients with HFpEF, outpatient diuretic intensification is frequent, associated with worse outcomes, and significantly reduced by spironolactone when included in an extended composite endpoint.
Answers are grounded in this paper and cite their sources.
Spironolactone was associated with fewer outpatient diuretic intensifications in HFpEF; hypothesis-generating and leaves causal benefit on hard outcomes open.
AIMS: Outpatient treatment for the worsening of signs and symptoms of heart failure (HF) is usually not incorporated in the main outcomes of HF trials. Patients with HF and a preserved ejection fraction (HFpEF) may experience frequent episodes of outpatient worsening HF. The aim of this study was to evaluate the frequency, prognostic impact, and the effect of spironolactone on outpatient diuretic intensification (ODI), among 1767 patients enrolled in TOPCAT-Americas. METHODS AND RESULTS: Time-updated Cox models and win ratio analysis. ODI was defined by a post-randomization loop diuretic dose increase or new initiation. The median follow-up was 2.9 years. At baseline, 1362 (77%) patients were taking loop diuretics. During the follow-up, 685 (38.8%) patients experienced ODI, which was associated with a higher risk of subsequent cardiovascular events and death [adjusted hazard ratio (HR) for HF hospitalization or cardiovascular death 1.67, 95% confidence interval (CI) 1.36-2.04; HR for cardiovascular death 2.17, 95% CI 1.64-2.87); and HR for all-cause mortality 1.75, 95% CI 1.41-2.16] (p < 0.001 for all outcomes). Adding ODI to the composite of HF hospitalization or cardiovascular death increased the event rate by three-fold in the placebo group (from 10.4 to 29.9 events per 100 person-years). Spironolactone treatment led to a 26% relative reduction of the extended composite of ODI or HF hospitalization or cardiovascular death (HR 0.74, 95% CI 0.65-0.85; p < 0.001) compared with a 16% relative reduction of HF hospitalization or cardiovascular death (HR 0.84, 95% CI 0.70-0.99; p = 0.044). Using win ratio provided similar estimates. CONCLUSION: In HFpEF, ODI was frequent and independently associated with subsequent cardiovascular events. Spironolactone significantly reduced an extended composite outcome incorporating ODI.
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Ferreira et al. (2021) conducted an RCT in Heart failure with preserved ejection fraction (HFpEF) (n=1,767). Spironolactone vs. Placebo was evaluated on Extended composite of outpatient diuretic intensification (ODI) or HF hospitalization or cardiovascular death (HR 0.74, 95% CI 0.65-0.85, p=<0.001). Spironolactone reduced an extended composite of outpatient diuretic intensification, HF hospitalization, or cardiovascular death (HR 0.74; 95% CI 0.65-0.85; p<0.001).
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