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Medicine Matters diabetes

HFpEF--Heart failure with preserved ejection fraction accounts for around 50 percent of all people living with heart failure and really HFpEF is driven by the presence of co-morbidities, co-morbidities such as type 2 diabetes, such as hypertension, such as obstructive sleep apnea and also HFpEF is more common in women compared to men in contrast with HFrEF which seems to be a male predominant condition, so it is something we very much need to be aware of in primary care, it can have a debilitating effect on quality and quantity of life, but sadly we lack robustly demonstrated evidence-based therapies for HFpEF unlike HFrEF where we know ACE inhibitors, ARBs,  beta blockers spironolactone and SGLT2 inhibitors sacubitril/valsartan can all have a significant impact on improving quality and quantity of life, but sadly that's not the case for HFpEF.



We've had a couple of trials we had the PARAGON-HF, which explored the impact of sacubitril/valsartan in HFpEF. It actually didn't meet its primary endpoint but it was found to have some beneficial effects in certain groups of individuals with HFpEF, particularly women, but also those perhaps at the lower range of HFpEF, so ejection fractions around about 47 percent and above. And actually good old-fashioned spironolactone – well established as a therapy for HFrEF – was also found to have some benefits in heft from the TOPCAT study, but this proved to be quite controversial actually because what they did with the TOPCAT study was essentially exclude a couple of sites: Russia and Republic of Georgia, and after they did that – they were deemed to be problematic sites – there were positive results for people with a preserved ejection fraction. So these were, perhaps a less robust demonstration of clinical benefits in HFpEF, so we really eagerly awaited the results of the EMPEROR-Preserved trial, looking at empagliflozin in a dedicated heart failure with preserved ejection fraction trial to see what, if any, impact empagliflozin has on people living with HFpEF, again irrespective of diabetes status.



EMPEROR-Preserved recruited nearly six thousand individuals living with HFpEF, with ejection fractions over forty percent and around forty 45 of the trial population were female, so large numbers and actually larger numbers of female participants than previous heart failure trials, so again very relevant to the primary outcome of the study.



From a primary care perspective there's much less awareness of HFpEF in primary care than say HFrEF, and so I'm hoping studies such as EMPEROR-Preserved will help improve awareness of HFpEF and ultimately help us in primary care better support our patients living with HFpEF.



The key finding of EMPEROR-Preserved was a significant-- clinically significant and statistically significant 21 percent reduction in the primary composite endpoint of hospitalization for heart failure or cardiovascular death.



So I know it's an overused term, but this is a game changer for people living with HFpEF, because as I've said we've had no real robustly demonstrated evidence-based therapies to date so this equated to a 3.3 percent absolute risk reduction and number needed to treat of around about 30 over 26 months to prevent one adverse cardiovascular death or hospitalization for heart failure. So this is-- these are compelling results and actually not far off the results of DAPA-HF and EMPEROR-Reduced, which looked at people living with HFrEF, so to be honest I found this quite surprising. Well we've seen the really beneficial effects of SGLT2 inhibitors in heart failure in a number of trials the previous SGLT2 cardiovascular outcome trials and then DAPA-HF and EMPEROR-Reduced. And just with the heterogeneous population of HFpEF, the different ranges of ejection fraction I wasn't convinced we would see such compelling benefits so it's great to see these very low-- relatively low numbers needed to treat.