Spironolactone Metabolites in TOPCAT — New Insights into Regional Variation

In a subgroup of TOPCAT participants assigned to spironolactone, the spironolactone metabolite canrenone was measured to assess adherence. Canrenone levels were undetectable in 30% of participants from Russia, as compared with only 3% from the United States and Canada. To the Editor: In the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial, patients with heart failure and preserved ejection fraction were randomly assigned to receive either spironolactone or placebo. The investigators found that the incidence of the primary composite end point of death from cardiovascular causes, hospitalization for heart failure, or resuscitated cardiac arrest was not significantly lower in the spironolactone group than in the placebo group, but the incidence of hospitalization for heart failure was significantly lower in the spironolactone group. 1 However, significant differences in the clinical profiles, event rates, and responses to . . .