In the TOPCAT study, spironolactone therapy did not reduce death from cardiovascular causes, aborted cardiac arrest, or hospitalization of patients with heart failure and preserved ejection fraction. In a post hoc analysis, the TOPCAT investigators examined the regional difference in clinical outcomes and responses to spironolactone within the study population. Compared with patients from Russia and Georgia, patients from the Americas had greater changes in potassium and creatinine levels in response to spironolactone treatment. Furthermore, the rates of the primary outcome were reduced by spironolactone in patients from the Americas, but not in patients from Russia and Georgia.