Renal outcomes in contemporary trials of heart failure

Attendees at the Irish Nephrology Society Annual Scientific Meeting 2023 heard from Dr Finnian McCausland, Associate Physician, Brigham and Women’s Hospital, Harvard Medical School, Boston, US, who discussed the high risk and prevalence of chronic kidney disease (CKD) in heart failure. Dr McCausland highlighted that CKD is associated with a 2.4-fold risk of death in acute heart failure and a 2.3-fold risk in chronic heart failure. He talked briefly about cardiorenal syndrome and its classifications based on The Consensus Conference of the Acute Dialysis Quality Initiative, and why “not all worsening renal failure is the same”. He discussed how declines in kidney function need to be interpreted in the context of decongestion and haemoconcentration, and the association between decongested heart failure and lower mortality, before examining renal outcomes in heart failure research.

Dr McCausland presented findings and a pooled analysis of data from major heart failure studies, including the OVERTURE trial, the PARADIGM-HF study, and the PARAGON-HF study, to investigate areas like RAAS inhibition (RASi) and renal outcomes in heart failure. He described how “sacubitril/valsartan reduced the risk of frequency of kidney events in patients with heart failure across the ejection fraction (EF) spectrum”. 

“The renal benefits were most apparent at higher EF, and the renal benefits were independent of baseline eGFR. Sacubitril/valsartan also slowed the rate of decline in eGFR vs active RASi trials across the EF spectrum.”

Moving on to what Dr McCausland termed “the hot news off the press”, he examined the relationship between dapagliflozin and kidney function during studies, including the DAPA-HF and DELIVER trials. “Did the cardiovascular composite outcomes differ according to baseline eGFR?” he asked. “Again, the answer is no. The treatment effect for cardiovascular benefits were consistent across the spectrum of eGFR, right down to below 40 and as low as 30 as patients were enrolled here, suggesting we should be comfortable prescribing these medications for patients with CKD, based on this trial, right down to a GFR of 30. And I’ll show you some evidence that suggests we should be comfortable a little bit lower as well.” 

Looking at clinical kidney outcomes, Dr McCausland acknowledged “there is a whole lot of debate”, and noted that many might say there is no evidence of kidney benefits in the data. However, he added “let’s think about this a little bit more… when you look at the slopes in eGFR, you’ll see patterns that are consistent with every other trial that’s been published with SGLT2 inhibitors so far; an acute decline in eGFR followed by stablisation. Do we interpret the overall slope? Do we ignore the acute decline? Do we focus on the chronic slope? There’s a whole lot of debate about that, but if we look overall and look at the chronic decline, there’s certainly a differential in favour of dapagliflozin at slowing kidney function decline.” 

Noting that dapagliflozin did slow the rate of decline in GFR vs placebo, he described this data as “reassuring”.

He said that “potentially, if these studies were longer, we may have seen some actual benefits in terms of kidney clinical outcomes”. Looking to the future, Dr McCausland discussed the potential of combination RASi and SGLT2 therapies and future clinical trials, saying “there is a lot of interest and a lot of movement in this area, and, I think, a lot more to come. Hopefully, we will see some positive data because we really need it in this population…. We have a lot more work to do.”