Spironolactone reduces cardiovascular events in HFpEF patients with increased LV mass or left atrial volume.
Photo by Ben Maffin / Unsplash
Key Takeaway
Note that spironolactone may reduce cardiovascular events in HFpEF subgroups with specific structural abnormalities, but data are from a post hoc analysis.
This post hoc analysis examined data from the TOPCAT randomized controlled trial, focusing on 757 subjects with heart failure with preserved ejection fraction (left ventricular ejection fraction ≥50%) and evidence of abnormal diastolic function. The investigation assessed the impact of spironolactone on cardiovascular mortality, heart failure hospitalization, and a composite outcome of cardiovascular mortality, heart failure hospitalization, and aborted sudden death.
In patients with increased left atrial volume index, spironolactone was associated with reduced cardiovascular mortality, with an adjusted hazard ratio of 0.48 (95% CI, 0.24-0.98; p=0.042). Similarly, in patients with increased left ventricular mass index, heart failure hospitalization decreased with an adjusted hazard ratio of 0.51 (95% CI, 0.32-0.80; p=0.009), and the composite outcome decreased with an adjusted hazard ratio of 0.63 (95% CI, 0.43-0.93; p=0.045).
Further analysis using propensity score matching in participants with both increased left atrial volume index and left ventricular mass index showed reduced cardiovascular mortality (adjusted hazard ratio 0.31; 95% CI, 0.11-0.92; p=0.039), reduced heart failure hospitalization (adjusted hazard ratio 0.26; 95% CI, 0.10-0.68; p=0.005), and a reduced composite outcome (adjusted hazard ratio 0.33; 95% CI, 0.15-0.72; p=0.006).
No specific safety data, adverse events, or tolerability information were reported in this analysis. The primary limitation is that this is a post hoc analysis, which may be subject to bias and does not establish causality. Consequently, these results should be interpreted with caution when considering spironolactone for HFpEF management outside the context of the original trial protocol.
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View Original Abstract ↓
BACKGROUND: It is unclear whether patients with heart failure with preserved ejection fraction respond to spironolactone based on cardiac structure or function.
METHODS: A post hoc analysis was performed among participants with left ventricular (LV) ejection fraction ≥50% and evidence of abnormal LV diastolic function or filling pressures in TOPCAT (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist Trial). Log-rank tests and Cox regression models were used for comparison between groups.
RESULTS: Totally, 757 subjects were qualified and stratified by parameters on cardiac structure or function. In patients with increased left atrial volume index, spironolactone reduced cardiovascular mortality (adjusted hazard ratio [HR], 0.48 [95% CI, 0.24-0.98]; =0.042, log-rank; interaction =0.045). Meanwhile, in patients with increased LV mass index, spironolactone decreased heart failure hospitalization (adjusted HR, 0.51 [95% CI, 0.32-0.80]; =0.009, log-rank; interaction =0.041) and the composite outcome of cardiovascular mortality, heart failure hospitalization, and aborted sudden death (adjusted HR, 0.63 [95% CI, 0.43-0.93]; =0.045, log-rank; interaction =0.029). Then, in participants with increased left atrial volume index and LV mass index, who matched at 1:1 ration by propensity score matching, spironolactone reduced cardiovascular mortality (adjusted HR, 0.31 [95% CI, 0.11-0.92]; =0.039, log-rank), heart failure hospitalization (adjusted HR, 0.26 [95% CI, 0.10-0.68]; =0.005, log-rank), and the composite outcome (adjusted HR, 0.33 [95% CI, 0.15-0.72]; =0.006, log-rank).
CONCLUSIONS: Spironolactone reduced cardiovascular mortality, heart failure hospitalization, or the composite outcome of cardiovascular mortality, heart failure hospitalization, and aborted sudden death in patients with heart failure with preserved ejection fraction with increased left atrial volume index or LV mass index.
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