More Good News for Empagliflozin in Patients With Heart Failure

Empagliflozin (Jardiance) was able to hit the pause button on renal decline in all patients with heart failure (HF), a researcher reported.

In the phase III EMPEROR-Preserved trial, among nearly 6,000 patients with chronic HF with preserved ejection fraction (HFpEF), empagliflozin was able to slow kidney function decline over the 172-week trial regardless of chronic kidney disease (CKD) status, reported Faiez Zannad, MD, PhD, of the Université de Lorraine in France at the American Society of Nephrology virtual Kidney Week.

Also, those on empagliflozin did not continue on a downward eGFR slope versus those on placebo, in a key secondary outcome. And patients with CKD on empagliflozin were able to maintain an eGFR slope difference of 1.4 mL/min/1.73 m²/year higher than those on placebo. Patients without CKD also maintained higher eGFR levels on average, with a 1.3 mL/min/1.73 m²/year slope difference versus placebo.

Patients that didn't yet have CKD at baseline were able to avoid a clinically relevant eGFR decline versus what was seen in the placebo group -- a drop of around 3.2 mL/min/1.73 m²/year, according to the researchers.

These reno-protective benefits also appeared to be maintained even after treatment discontinuation. During a withdrawal period following the study's conclusion, patients that were off treatment for anywhere between 23 to 45 days kept up a significantly higher eGFR versus placebo (2.4 mL/min/1.73 m², 95% CI 1.6-3.2). This treatment difference from baseline to the off-treatment period was the same for those with or without CKD.

And all patients on empagliflozin, regardless of CKD status, saw a lower risk for acute kidney injury versus placebo (HR 0.73, 95% CI 0.56-0.95), while among all patients with normo-microalbuminuria, also with or without CKD, those on treatment saw a significantly lower risk for the progression to macroalbuminuria (HR 0.82, 95% CI 0.68-0.98).

"Despite the known acute hemodynamic effects on eGFR, empagliflozin was associated with a reduced risk of investigator-reported acute kidney injury and progression to macroalbuminuria, irrespective of CKD status," Zannad reiterated.

The current findings build upon those from the EMPEROR-Reduced trial, presented at 2020 Kidney Week. That study found similar results in adults with HF with reduced EF, down to an eGFR of 20 mL/min/1.73m². That trial also showed a reduced risk of kidney events in patients regardless of baseline CKD status.

Based on that trial, the FDA expanded the label of empagliflozin in August 2021 to include an indication for the reduction of risk of cardiovascular death (CVD) and HF hospitalization. Dapagliflozin (Farxiga) was the first agent in this class to gain this indication in May 2020.

"Anything I'm saying [here], I have said last year with EMPEROR-Reduced," noted Zannad. "This is really important progress in the treatment of all heart failure patients, and certainly with less issues when they have CKD in combination with heart failure." He added that the outcomes may even extend to the entire class of SGLT-2 inhibitors.

The current trial enrolled patients 18 years and older who had chronic HF (New York Heart Association class II-IV) with an EF over 40%. The 5,988 patients randomized included a mix of those with and without type 2 diabetes. At baseline, the CKD population (53.5%, n=3,198) had an average eGFR of 46.3 mL/min/1.73 m², whereas the non-CKD population (46.5%, n=2,778) had an eGFR of 77.1 mL/min/1.73 m².

Those randomized to receive treatment were given once-daily 10 mg empagliflozin and were follow-up for a median of 26.2 months.

Trial results were reported at the 2021 European Society of Cardiology virtual congress, and the study met its primary endpoint -- a significant reduction in CVD or HF hospitalization (HR 0.79, 95% CI 0.69-0.90). There was also a significant reduction in first and recurrent HF hospitalization, which was a key secondary endpoint (HR 0.73, 95% CI 0.61-0.88).

There was a higher rate of genital infections in the empagliflozin group, which is to be expected with a SGLT-2 inhibitor. Overall, those with CKD at baseline tended to see a higher rate of any adverse events, the researchers reported.

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