What were the findings of the post-hoc analyses of the TOPCAT trial?
The post-hoc analyses of the TOPCAT trial noted a substantial (~4 fold) difference in the primary composite outcome (time to cardiovascular death, aborted cardiac arrest, or hospitalisation for heart failure), as well as substantial differences in baseline characteristics, between patients randomised from Russia and Georgia compared with patients from the United States, Canada, Brazil and Argentina (the Americas). In the Americas, a substantial and clinically important reduction in the primary composite outcome was seen in patients with a phenotype more typical of HFPEF as defined in the UK. A similar difference was found across the other clinical outcomes recorded. In the post-hoc analysis, the study authors examined the baseline characteristics and responses to treatment in each region, and speculated that the clinical diagnostic criteria for heart failure with preserved ejection fraction were not uniformly interpreted or applied. It noted that the death rate of the cohort from Russia/Georgia was more reflective of the general population than of patients with heart failure. The authors concluded that 2 distinctly different populations were enrolled in the 2 regions.