Dapagliflozin Slows the Rate of Kidney Decline

Finnian McCausland, MD

New data continues to support the use of dapagliflozin to preserve kidney function and reduce the odds of negative cardiovascular outcomes.

A team, led by Finnian R. McCausland, Brigham and Women’s Hospital, assessed the influence of baseline kidney function on cardiovascular outcomes and the effect of dapagliflozin on renal outcomes and eGFR trajectory.

The data was presented as a late-breaking abstract during the 2022 American Society of Nephrology (ASN) Annual Meeting in Orlando.

The Treatments

SGLT2 inhibitors are known to reduce the risk of heart failure events and slow the progression of kidney disease in patients with heart failure and reduced ejection fraction.

However, dapagliflozin significantly reduced the primary composite outcome of cardiovascular death or worsening heart failure in patients with heart failure and mildly reduced or preserved ejection fraction in the DELIVER study.

In the study, the investigators randomized 6263 patients with ejection fraction >40% and eGFR ≥25 ml/min/1.73m² to dapagliflozin 10mg per day or placebo between July 1 and September 18, 2022. The mean age of the patient population was 72 years.

Outcomes

The investigators sought main outcomes of whether baseline kidney function modified the treatment effect on the primary outcome of cardiovascular death or worsening heart failure.

Each patient had whether baseline kidney function modified the treatment effect on the primary cardiovascular outcome and its components assessed.

The investigators also examined the treatment effect on eGFR slope and a composite kidney outcome ≥50% decline in eGFR, eGFR <15 ml/min/1.73m², and renal death in the prespecified exploratory analyses.

The mean eGFR was 61±19 ml/min/1.73m² and 49% (n = 3070) had eGFR <60 ml/min/1.73m². Dapagliflozin was not influenced by baseline eGFR (HR, 0.84; 95% CI, 0.70-1.00 for eGFR ≥60 and HR, 0.81; 95% CI, 0.69-0.94 for eGFR<60; P = 0.76).

The overall incidence rate over a median follow-up of 2.3 years of kidney composite outcome was 1.1 events per 100 patient-years.

The treatment did not reduce the kidney composition outcomes, which occurred in 2.5% (n = 77) of the dapagliflozin group and 71 patients in the placebo group (HR, 1.09; 95% CI, 0.79-1.50).

Finally, dapagliflozin attenuated the decline in eGFR between month 1-36 compared to placebo (difference, 1.4 ml/min/1.73m2/year; 95% CI, 1.0-1.8).

“Baseline kidney function did not modify the benefit of dapagliflozin in patients with HF with mildly reduced or preserved EF. Dapagliflozin slowed the rate of decline in eGFR to a greater extent than placebo,” the authors wrote.

The study, “Dapagliflozin and Kidney Outcomes in Heart Failure With Mildly Reduced or Preserved Ejection Fraction: Results From DELIVER,” was published online by ASN.