Is Spironolactone effective against diastolic dysfunction?

From the Guidelines

Spironolactone may be effective in improving diastolic function in patients with heart failure with preserved ejection fraction (HFpEF), particularly in those with elevated BNP levels and certain clinical characteristics.

Key Points

• The TOPCAT trial showed a small reduction in the composite endpoint of death, aborted cardiac death, and HF hospitalization with spironolactone, although it did not reach statistical significance 1.
• A post-hoc analysis of the TOPCAT trial suggested efficacy of spironolactone in patients with HFpEF in the Americas, but not in Russia/Georgia 1.
• Mechanistic studies have suggested that mineralocorticoid receptor antagonists, such as spironolactone, can improve measures of diastolic function in patients with HFpEF, possibly by a similar effect on remodeling 1.
• The use of spironolactone in patients with HFpEF may be considered in those with certain clinical characteristics, such as EF ≥45%, elevated BNP levels or HF admission within 1 year, estimated glomerular filtration rate >30 mL/min, creatinine <2.5 mg/dL, and potassium <5.0 mEq/L, with close monitoring of potassium and renal function 1.

Important Considerations

• Careful monitoring of potassium, renal function, and diuretic dosing is necessary to minimize the risk of hyperkalemia and worsening renal function when using spironolactone in patients with HFpEF 1.
• The effectiveness of spironolactone in patients with HFpEF may vary depending on regional and individual factors, and confirmatory studies are required to fully establish its efficacy 1.

The FDA Drug Labels for spironolactone (PO) do not address this question.

From the Research

Effectiveness of Spironolactone Against Diastolic Dysfunction

• The effectiveness of spironolactone against diastolic dysfunction has been investigated in several studies 2, 3, 4, 5, 6.
• A study published in the Journal of human hypertension found that short-term spironolactone therapy did not lead to improvement in diastolic function despite rapid reversal of left ventricular hypertrophy in patients with resistant hypertension 2.
• In contrast, a study published in the Journal of cardiac failure found that spironolactone treatment improved diastolic function by significantly increasing early diastolic tissue Doppler velocity of the lateral mitral annulus and reducing the mitral peak E velocity to lateral e' ratio in elderly women with heart failure and preserved left ventricular ejection fraction 3.
• Another study published in JAMA found that long-term aldosterone receptor blockade with spironolactone improved left ventricular diastolic function but did not affect maximal exercise capacity, patient symptoms, or quality of life in patients with heart failure with preserved ejection fraction 5.
• The effectiveness of spironolactone in patients with resistant arterial hypertension has also been investigated, with one study finding that spironolactone treatment is effective to a similar extent both in patients with and without a secondary cause of hypertension and regardless of the baseline value of systolic BP 6.

Key Findings

• Spironolactone may not lead to improvement in diastolic function in patients with resistant hypertension despite rapid reversal of left ventricular hypertrophy 2.
• Spironolactone treatment can improve diastolic function in elderly women with heart failure and preserved left ventricular ejection fraction 3.
• Long-term aldosterone receptor blockade with spironolactone can improve left ventricular diastolic function but may not affect maximal exercise capacity, patient symptoms, or quality of life in patients with heart failure with preserved ejection fraction 5.
• Spironolactone treatment is effective in patients with resistant arterial hypertension regardless of the presence of a secondary cause of hypertension or baseline systolic BP value 6.