At the European Society of Cardiology 2023 Congress in Amsterdam, investigators presented late-breaking data on the benefit-to-risk ratio of continuing treatment with dapagliflozin in patients with heart failure and advancing chronic kidney disease (CKD): deterioration in kidney function to an estimated glomerular filtration rate (eGFR) less than 25 mL/min/1.73m2.
Investigators pooled data from the DELIVER and DAPA-HF trials involving 11,007 patients with heart failure and preserved, mildly reduced, or reduced ejection fraction. Of these, 347 patients (3.2%) had an eGFR that declined to less than 25 mL/min/1.73m2 during the trials. The time to deterioration of kidney function was similar for patients randomly assigned to dapagliflozin or placebo: 120 vs 121 days.
The risk for the primary composite outcome of cardiovascular death or worsening heart failure was 87% higher for patients with vs without renal decline to less than 25 mL/min/1.73m2, further reinforcing the adverse connection between heart failure and kidney disease, Scott D. Solomon, MD, of Harvard Medical School in Boston, Massachusetts, reported on behalf of his research team. The primary outcome occurred in 18.6 vs 10.2 per 100 person-years of the groups, respectively.
Dapagliflozin treatment vs placebo, however, was significantly associated with a 73% reduced risk of the primary outcome in patients with a persistent eGFR less than 25 mL/min/1.73m2, which was greater than the 21% risk reduction observed in those without deterioration of kidney function to that level. In those with an eGFR decline to less than 25 mL/min/1.73m2 at least once, the absolute risk reduction was higher among patients who experienced renal deterioration was 10.7 vs 2.4 per 100 person-years, respectively.
Approximately three-quarters of patients with eGFR decline to less than 25 mL/min/1.73m2 remained on dapagliflozin or placebo, as randomly assigned. Rates of serious adverse events (AEs), renal AEs, AE leading to volume depletion, renal AE, and AE leading to drug discontinuation or interruption appeared lower than placebo among patients with renal deterioration to 25 mL/min/1.73m².
The safety of dapagliflozin appeared consistent, including among patients who remained on study drug after eGFR fell to below 25ml/min/1.73m2, Dr Solomon reported.
The benefit-to-risk ratio may favor continued treatment with dapagliflozin in patients with heart failure and deterioration in kidney function below eGFR 25 mL/min/1.73m2, he concluded.
He cautioned that current FDA labelling does not recommend initiation of dapagliflozin in patients with an eGFR less than 25 mL/min/1.73m2.
Disclosure: This research was supported by AstraZeneca. Please see the original reference for a full list of disclosures.
Solomon SD, Chatur S, Vaduganathan M, et al. Effects of dapagliflozin in patients with heart failure and deterioration of kidney function to eGFR less than 25 mL/min/1.73m2: A participant-level pooled analysis of the DAPA-HF and DELIVER Trials. ESC Congress 2023; August 25-28; Amsterdam.