SGLT2i reduces risk of kidney failure, CV death or HF hospitalization, and all-cause mortality in CKD

Dapagliflozin in Patients with Chronic Kidney Disease DAPA-CKD

Presented at the ESC congress 2020 by: Prof. Hiddo Heerspink, PhD, Groningen, The Netherlands

Introduction and methods

Patients with chronic kidney disease (CKD) are at high risk of adverse kidney and CV outcomes. The DAPA-CKD trial investigated the effect of SGLT2 inhibitor dapagliflozin, compared to placebo, on the risk of renal and CV events in CKD patients, with or without T2DM.

A total of 4304 patients (≥18 years of age) from 286 centers in 21 countries were included in the trial. Patients had an eGFR ≥25 and ≤75 mL/min/1.73m², urinary albumin to creatinine ratio between ≥200 mg/g and ≤5000 mg/g, and were already receiving a stable maximum tolerated dose of either an angiotensin-converting enzyme (ACE) inhibitor or an angiotensin receptor blocker (ARB) as background therapy. Average age was 61.8 years, 66.9% were male and 67.5% had T2DM. Patients were randomized to receive either dapagliflozin 10 mg one daily or matching placebo.

The primary composite endpoint was worsening kidney function (defined as ≥50% sustained decline in eGFR or onset of end-stage kidney disease), or renal or CV death. The first secondary endpoint was a composite of worsening kidney function, or death from kidney failure. The second secondary endpoint was a composite of HF hospitalization or CV death. The third secondary endpoint was all-cause mortality.

The trial was stopped early due to overwhelming efficacy. This decision was made following a recommendation from an independent Data Monitoring Committee. The median follow-up was 2.4 years.

Main results

• Dapagliflozin significantly reduced the risk of the primary endpoint with 39%, compared to placebo (HR 0.61, 95%CI 0.51-0.72, P=0.000000028). The benefit of dapagliflozin on the primary endpoint was consistent in patients with and without T2DM.
• Compared to placebo, dapagliflozin reduced the risk on all three secondary endpoints: The composite of worsening kidney function or death from kidney failure (first secondary endpoint HR=0.56, 95%CI 0.45-0.68, P<0.0001), the composite of HF hospitalization or CV death (second secondary endpoint HR 0.71, 95%CI 0.55-0.92, P=0.0089, and all-cause mortality (third secondary endpoint HR 0.69, 95%CI 0.53-0.88, P=0.0035).
• The proportion of patients who discontinued the drug or who experienced a serious adverse event in the placebo group (5.7% and 33.9%, respectively) was similar to dapagliflozin group (5.5% and 29.5%, respectively). Diabetic ketoacidosis occurred in two patients in the placebo group and was not reported in the dapagliflozin group. Neither diabetic ketoacidosis nor severe hypoglycemia were reported in patients without T2DM.

Conclusion

Dapagliflozin significantly reduced the risk of kidney failure, CV death or HF hospitalization, and all-cause mortality in patients with CKD, with and without T2DM, compared to placebo.

- Our reporting is based on the information provided at the ESC congress -

Watch a video by prof. Heerspink on this trial