Subject to Notice of rights. ISBN: 978-1-4731-3093-7 Research recommendation No recommendation reduced hospitalisation. Due to the uncertainty on the clinical benefit of MRAs in this population, and the lack of published economic evaluations, the committee could not make a clear judgement on the cost-effectiveness of MRAs for those with chronic heart failure with preserved ejection fraction and therefore did not make a recommendation. Other considerations The majority of the evidence in this review was from the TOPCAT trial265 a large, high quality study comparing spironolactone with placebo in patients with heart failure with preserved ejection fraction. The main report of this study was published in 2014, but the committee was aware of the subsequent post-hoc analyses of this study investigating regional variation in the results259 . The post-hoc analyses 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. 