What effects does the use of aldosterone receptor antagonists have in patients with HFpEF?
Mechanistic studies have suggested that mineralocorticoid receptor antagonists can improve measures of diastolic function in patients with HFpEF, possibly by a similar effect on remodeling.83,168 The TOPCAT (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist) trial166 investigated the effects of spironolactone on a combined endpoint of death, aborted cardiac death, and HF hospitalization in patients with HFpEF. A small reduction (HR=0.89) in this composite endpoint did not reach statistical significance, although HF hospitalization was reduced (HR=0.83); known side effects of hyperkalemia and rising creatinine were seen more commonly in the treatment group.166 An unusual amount of regional variation was seen in this trial, prompting a post-hoc analysis167 that showed that rates of the primary endpoint were 4-fold lower in Russia/Georgia than in North America and South America (the Americas).