Continuing the steady flow of positive findings in studies of SGLT2 inhibitors, researchers now report that dapagliflozin can slow the decline of failing kidneys and thus lower the risk of kidney failure, premature death, or hospitalization for heart failure in patients with chronic kidney disease.
Those findings emerged from the DAPA-CKD trial, which was presented as a Hot Line at the European Society of Cardiology, ESC 2020: The Digital Experience.
DAPA-CKD compared dapagliflozin (10 mg) on top of background ACE-inhibitor or angiotensin receptor blocker (ARB) treatment to ACEi or ARB plus placebo in 4,304 patients with CKD, with or without type 2 diabetes.
The primary composite endpoint was worsening kidney function (defined as >50% sustained decline in estimated glomerular filtration rate [eGFR] or onset of end-stage kidney disease) or death due to kidney disease or cardiovascular disease. The secondary endpoints were, in hierarchical order:
- A composite endpoint of worsening kidney function (defined as >50% sustained decline in eGFR or onset of end-stage kidney disease) or death from kidney failure.
- A composite endpoint of hospitalization for heart failure or cardiovascular death.
- All-cause mortality.
“During a median follow-up of 2.4 years, there were 197 primary endpoint events with dapagliflozin and 312 with placebo. The hazard ratio (HR) for the primary endpoint was 0.61 (95% confidence interval [CI) 0.51–0.72; P=0.000000028). The benefit of dapagliflozin on the primary endpoint was consistent in patients with and without type 2 diabetes,” said principal investigator Hiddo J.L. Heerspink, PhD, of University Medical Centre Groningen, the Netherlands.
Moreover, HRs (favoring dapagliflozin) for secondary endpoints were:
- 0.56 (95% CI 0.45–0.68; P<0.0001) for worsening renal function or death from kidney failure.
- 0.71 (95% CI 0.55–0.92; P=0.0089) for hospitalization for heart failure or cardiovascular death.
- 0.69 (95% CI 0.53–0.88=0.0035) for all-cause mortality.
In DAPA-HF, reported at the ESC in 2019, the SGLT2i on top of standard medical therapy was shown to reduce mortality and hospitalizations in heart failure patients with reduced ejection faction. BreakingMED asked Heerspink if the heart failure benefit seen in DAPA-CKD was limited to patients with reduced ejection fraction; however, Heerspink said he and his colleagues did not analyze findings by ejection fraction.
Heerspink said the safety and tolerability of dapagliflozin was similar to that observed other trials.
Diabetic ketoacidosis was not reported in any patient randomized to dapagliflozin and occurred in two patients in the placebo group. Neither diabetic ketoacidosis nor severe hypoglycemia were observed in patients without type 2 diabetes.
“DAPA-CKD showed that dapagliflozin reduced the risk of worsening kidney function or death from cardiovascular or kidney disease in patients with chronic kidney disease with and without type 2 diabetes,” Heekspink said. “The results highlight the medicine’s potential to benefit patients with chronic kidney disease who are in need of improved treatment options.”
Peggy Peck, Editor-in-Chief, BreakingMED™
Cat ID: 127
Topic ID: 81,127,102,204,3,305,446,12,187,307,127,415,192,925,203