Regional differences in heart failure with preserved ejection fraction trials: when nephrology meets cardiology but east does not meet west.

In heart failure (HF) with reduced ejection fraction (HF-REF), renin-angiotensin-aldosterone system (RAAS) inhibitors are the Level 1A evidence-based cornerstones of pharmacological treatment. As a result of trial-based progress in medical therapy in the last 2 decades, mortality associated with HF-REF has declined almost 3-fold. In sharp contrast, HF with preserved ejection fraction (HF-PEF) is still lacking evidence-based therapies.12 Indeed, the 3 major outcome trials performed in HF-PEF with RAAS inhibitors did not meet their primary end points.3-5 A post hoc analysis of the latest trial, TOPCAT (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist), identified an unusually large difference (=4-fold) in the placebo group primary event rate of patients randomized from Russia and Georgia (Russia/ Georgia) compared with those enrolled from the United States, Argentina, Brazil, and Canada (ie, the Americas).5