European Society of Cardiology

European Society of Cardiology

Source:

Heerspink H. Hot Line: DAPA-CKD. Presented at: European Society of Cardiology Congress; Aug. 29-Sept. 1, 2020 (virtual meeting).

Disclosures: The DAPA-CKD trial was funded by AstraZeneca. Heerspink reports he consults for AbbVie, AstraZeneca, Bayer, Boehringer Ingelheim, Chinook, CSL Pharma, Gilead, Janssen, Merck, Mundi Pharma, Mitsubishi Tanabe, Novo Nordisk and Retrophine and has received research support from AbbVie, AstraZeneca, Boehringer Ingelheim and Janssen.
August 30, 2020
5 min read
Save

Dapagliflozin cuts renal, CV events in CKD, regardless of diabetes status

Source:

Heerspink H. Hot Line: DAPA-CKD. Presented at: European Society of Cardiology Congress; Aug. 29-Sept. 1, 2020 (virtual meeting).

Disclosures: The DAPA-CKD trial was funded by AstraZeneca. Heerspink reports he consults for AbbVie, AstraZeneca, Bayer, Boehringer Ingelheim, Chinook, CSL Pharma, Gilead, Janssen, Merck, Mundi Pharma, Mitsubishi Tanabe, Novo Nordisk and Retrophine and has received research support from AbbVie, AstraZeneca, Boehringer Ingelheim and Janssen.
You've successfully added to your alerts. You will receive an email when new content is published.

Click Here to Manage Email Alerts

We were unable to process your request. Please try again later. If you continue to have this issue please contact customerservice@slackinc.com.

In the DAPA-CKD trial, treatment with the SGLT2 inhibitor dapagliflozin reduced risk for worsening renal function and death due to CVD or renal disease in patients with chronic kidney disease, both with and without type 2 diabetes.

Hiddo J.L. Heerspink

“The DAPA-CKD trial has shown dapagliflozin’s potential as a long-awaited new treatment option for patients with chronic kidney disease,” Hiddo J.L. Heerspink, PhD, clinical pharmacologist in the department of clinical pharmacy and pharmacology at University Medical Center Groningen, Netherlands, said during a press conference at the European Society of Cardiology Congress.

Kidneys 2019 Adobe
Source: Adobe Stock.

During a median follow-up of 2.4 years, the primary composite endpoint of worsening renal function — defined as at least a 50% sustained decline in estimated glomerular filtration rate or onset of end-stage renal disease — or death due to renal disease or CVD was reduced by 39% with dapagliflozin 10 mg (Farxiga, AstraZeneca) compared with placebo (HR = 0.61; 95% CI, 0.51-0.72). Heerspink reported 197 primary endpoint events in the dapagliflozin group vs. 312 events in the placebo group.

More than 67% of patients in DAPA-CKD had diabetes at baseline. The effect of dapagliflozin on the primary endpoint was consistent in patients either with (HR = 0.64; 95% CI, 0.52-0.79) or without (HR = 0.5; 95% CI, 0.35-0.72) type 2 diabetes, Heerspink said during the Hot Line presentation. The effects were also consistent in prespecified subgroup analyses based on urinary albumin creatinine ratio and eGFR at baseline.

In addition, dapagliflozin reduced all three secondary endpoints compared with placebo:

  • 44% reduction in worsening renal function or death from renal failure (HR = 0.56; 95% CI, 0.45-0.68).
  • 31% reduction in all-cause mortality (HR = 0.69; 95% CI, 0.53-0.88).
  • 29% reduction in HF hospitalization or CV death (HR = 0.71; 95% CI, 0.55-0.92).

In addition, Heerspink said dapagliflozin also significantly reduced the prespecified clinically meaningful and patient-oriented endpoint of chronic dialysis, kidney transplantation or renal death.

As Healio previously reported, DAPA-CKD was stopped early in March after investigators reported an “overwhelming benefit” for the primary outcome.

The safety and tolerability of dapagliflozin was consistent with its established profile, he said. Discontinuation of treatment due to an adverse event occurred in 5.5% of the dapagliflozin group vs. 5.7% of the placebo group. The proportion of patients that experienced a serious adverse event was 29.5% with dapagliflozin vs. 33.9% with placebo. Diabetic ketoacidosis was not reported in any patient assigned dapagliflozin, and there were no reports of diabetic ketoacidosis or severe hypoglycemia in patients with diabetes, Heerspink said.

“Last year, we did this [trial] in HF. We now demonstrate similar effects, but in people with chronic kidney disease,” he said during the Hot Line presentation.

The phase 3 DAPA-CKD trial enrolled 4,304 patients at 386 centers in 21 countries. The average age was 62 years and 67% were men. At baseline, all patients had an eGFR 25 and 75 mL/min/1.73 m2, had a urinary albumin creatinine ratio of 200 mg/g to < 5,000 mg/g and were already receiving stable, maximum-tolerated background therapy with an ACE inhibitor or angiotensin receptor blocker for at least 4 weeks.

In May, dapagliflozin was approved by the FDA to reduce risk for CV death and hospitalization for HF in adults with HF with reduced ejection fraction (HFrEF), with and without type 2 diabetes. Dapagliflozin is currently being assessed in patients with HF with preserved EF (HFpEF) in the DELIVERY trial, in patients with both HFrEF and HFpEF in the DETERMINE trial and in patients without type 2 diabetes following an MI in the DAPA-MI trial, according to a press release from AstraZeneca.