Empagliflozin for HF shows similar effect on kidney function regardless of diabetes status
In patients with HF, empagliflozin showed similar effects on estimated glomerular filtration rate, regardless of diabetes at baseline, and demonstrated safety and tolerability in line with the drug’s safety profile, a speaker reported.
According to an analysis of the EMPERIAL-Reduced and EMPERIAL-Preserved trails presented at the virtual Heart Failure Society of America Scientific Meeting, patients with HF and baseline estimated glomerular filtration rate (eGFR) of at least 20 mL/min/1.73 m2 experienced similar changes in eGFR after initiating and discontinuing empagliflozin (Jardiance, Boehringer Ingelheim/Eli Lilly), despite presence of baseline diabetes.
Healio previously reported on the announcement of the empagliflozin fast track designation from the FDA for the prevention of HF hospitalization and all-cause mortality in adults with a prior MI, with or without diabetes.
“In patients with heart failure included in the EMPERIAL study with eGFRs as low as 20 mL/min/1.73 m2, the changes in GFR after initiation and discontinuation of treatment were similar to eGFR changes on and off treatment that you generally see in type 2 diabetes patients without heart failure,” Stefan D. Anker, MD, PhD, of the Berlin-Brandenburg Center for Regenerative Therapies and the department of cardiology at Charité University in Berlin, Germany, said during his presentation. “There were no surprises or differences between the diabetics and nondiabetics with heart failure. If you focus on those events, they are consistent with the known safety profile and, if anything, less than expected. So really a very well-tolerated treatment.
“Very few events triggered discontinuation of treatment,” Anker said during the presentation. “[There were no instances] of ketoacidosis overall, very few cases of genital infection and only a total of five cases of bone fracture, but they all occurred in the diabetic patients and were equally distributed between groups. Hypoglycemia events were also not increased.”
Investigators utilized data from the EMPERIAL trials to determine the effects of the SGLT2 inhibitor empagliflozin on eGFR in patients with HF, with and without diabetes at baseline. Both trials (EMPERIAL-Reduced, n = 312; EMPERIAL-Preserved, n = 315) enrolled patients with HF and, for 12 weeks, they received empagliflozin 10 mg daily.
The EMPERIAL trials evaluated the effect of empagliflozin by measuring changes in 6-minute walk test distance, for which they demonstrated no significant impact of empagliflozin compared with placebo.
In this analysis, researchers observed a –3.3 mL/min/1.73 m2 between-group difference at 12 weeks for eGFR among patients taking empagliflozin compared with placebo. After treatment discontinuation, there was no significant change in the placebo group while the empagliflozin group experienced a 3.9 mL/min/1.73 m2 increase in eGFR.
When patients were stratified by diabetes status, the nondiabetic group experienced similar changes in eGFR by 12 weeks and through discontinuation. However, among patients with diabetes, those who received empagliflozin experienced a slight drop in eGFR by week 12, which increased to above baseline levels after discontinuation.
“It is well known that the reduction in eGFR is seen early after the start of treatment with empagliflozin, but during the follow-up assessment [eGFR] goes back up. You have a reduction at the end of the 12th week of 3.3 mL/min/1.73 m2 in empagliflozin,” Anker said during the presentation. “You have a smaller reduction in the placebo group, but all of this is reversed at the end of the follow-up with a 1-week washout period where, in the end, the eGFR is even higher in the patients on empagliflozin than those on placebo. If you specifically look at this by diabetic status, nondiabetic patients very much run parallel throughout the whole study. It was a different picture for diabetic patients, where you have a drop in eGFR for patients on empagliflozin, but a strong increase at the end of the follow-up with the washout period.”
Among patients without diabetes, those who received empagliflozin experienced fewer adverse events (58 vs. 74) and serious adverse events (13 vs. 26) compared with the placebo group. The incidence of adverse events was higher among the diabetes group, but similar between those who received empagliflozin and placebo.
“Even though the 6-minute walk turned out to be helpful in seeing improvement in patients who were severely limited with pulmonary hypertension, its use in heart failure has not tracked with proven therapies, which improves survival or decrease hospitalization,” Stephen S. Gottlieb, MD, professor of medicine at the University of Maryland School of Medicine in Baltimore, said during a discussant presentation. “A patient’s goal is not to walk further in 6 minutes. Of course, unless they have an app that is measuring it. But I’m not going to be concerned that the distance walked in 6 minutes was unchanged. This study presented by Dr. Anker should remind us that surrogate endpoints can be misleading and are not what our patients care about. It also reminds us that acute adverse effects, if well tolerated, should not blind us from long-term benefit, a lesson we learned many years ago when the heart failure community demonstrating the benefit of beta-blockers. In conclusion, that is still true today.”
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Anker SD, et al. Late-breaking clinical trials I. Presented at: Heart Failure Society of America Scientific Meeting; Sept. 30-Oct. 6, 2020 (virtual meeting).
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