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Empagliflozin Cuts Risk of CV, Renal Events in Heart Failure Regardless of CKD Status

— EMPEROR-Reduced trial included people with and without diabetes

MedpageToday

Results from the exploratory sub-analysis EMPEROR-Reduced phase III trial showed that empagliflozin reduced the risk of adverse cardiovascular and kidney events in adults with heart failure with reduced ejection fraction (HFrEF) regardless of chronic kidney disease status at baseline.

The findings were Circulation and presented virtually at the recent Kidney Week 2020 Meeting by Emperor program clinical investigator , of the University of Lorraine in France. In this 51˶ video, Zannad presents the key results and takeaways from the study.

Following is a transcript of his remarks:

Prevalence of heart failure and kidney disease are increasing. Patients with heart failure with reduced ejection fraction have a poor prognosis, particularly if accompanied by kidney impairment and vice versa. For nearly 2 decades, the only drugs with proven effect for slowing the progression of proteinuric CKD were RAS inhibitors. Within this context, in the EMPEROR-Reduced trial, we evaluated the effects of empagliflozin in a broad population of patients with chronic HFrEF with and without diabetes. The population was enriched for more severe left ventricular systolic dysfunction at a marked increase in natriuretic peptides. Remarkably, patients were enrolled down to an eGFR of 20 mL/min/1.73m2, and there was no inclusion criteria based on albuminuria.

The trial has three endpoints, one primary and two secondary. All of them were tested in hierarchical manner and all of them were met. You can see that adjudicated CV death or heart failure hospitalization was decreased by 25%. And this was statistically significant, adjudicated first and recurrent heart failure hospitalization would decrease by 30%. And the key secondary endpoint, which is slowing the slope of eGFR decline, was met also statistically significantly.

So, this is the depiction of the slope where you can see that in under background therapy, there is an enjoyable decline in eGFR in patients with HFrEF, which was slowed by the use of empagliflozin. And you can see that the early transient decline in eGFR, which was seen in some patients, does not deprive patients from benefit of empagliflozin. We have looked at that carefully and there is no excess rate of acute kidney injury in patients with this dip.

These are the major outcomes, kidney outcomes, which is sustained profound severe renal outcomes, which had declined about 40% of eGFRs of below 15 mL, or entering chronic dialysis or renal death -- and this was remarkably decreased by 50% overall.

We have looked at the consistency with DAPA-HF, the other twin trial in HFrEF with dapagliflozin. And although in DAPA-HF the renal outcome didn't come out statistically significant, the totality of evidence shows actually that SGLT2 inhibition decreases robustly 48%, 38% the point estimate of first composite kidney outcome. And this analysis allows an assessment of the long-term effects of treatment on kidney function, unconfounded by the presence of empagliflozin. It shows kidney function after treatment discontinuation at the end of the trial was better if patients received empagliflozin treatment, irrespective of prevalence CKD at baseline.

And these are the hard outcomes. And again, whether the patients had or did not have CKD at baseline, they benefited equally from preventing renal outcomes of sustained profound decline in renal function, entry to dialysis, or renal death.

Now, when it comes to safety, as expected, there were more adverse events in patients with CKD than patients without CKD, but overall, whether in patients with or without CKD, empagliflozin did not produce any excess adverse event as compared to placebo. Empagliflozin improved consistently CV and kidney outcomes in patients with and without prevalent CKD at baseline and across the full spectrum of kidney function down to an eGFR to 20 mL. Despite the known acute hemodynamic effects, empagliflozin was not associated with excess risk of investigator-reported acute kidney injury, irrespective of CKD status. And finally, empagliflozin was safe, including in patients with severely impaired kidney function.

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    Greg Laub is the Senior Director of Video and currently leads the video and podcast production teams.