Reduced worsening of kidney disease or CV death by SGLT2i in CKD patients

AHA 2022 In the EMPA-KIDNEY trial, use of empagliflozin reduced the outcome of worsening of kidney disease or CV death compared with placebo in CKD patients. In addition, results of a meta-analysis of 13 SGLT2i trials in high-risk patients were presented.

Presented at the AHA Scientific Sessions 2022 by: David Preiss, PhD - Oxford, UK

Introduction and methods

Use of SGLT2 inhibitors reduces important clinical events in high-risk patients. Benefits occur regardless of presence of CVD or diabetes in these high-risk patients. The CV benefits of treatment with SGLT2 inhibitors in patients with chronic kidney disease may be similar to benefits in other high-risk populations. This was studied in the EMPA-KIDNEY trial.

EMPA-KIDNEY was a RCT of 6609 patients with chronic kidney disease who were randomized to the SGLT2 inhibitor empagliflozin or placebo. The effect of treatment on CVD, progression of kidney disease, and the need for hospitalization in patients with chronic kidney disease was investigated. Mean follow-up was 2.0 years.

In addition, a meta-analysis of 13 major trials of SGLT2i therapies involving 90,000 patients was performed. The effect of treatment on CVD and other outcomes was examined in 3 groups of high-risk patients: participants with T2DM with or at high risk of CVD (4 trials), heart failure (5 trials) or chronic kidney disease (4 trials).

Main results

EMPA-KIDNEY trial results

• Treatment with empagliflozin reduced progression (i.e. worsening) of kidney disease or CV death by 28% compared to placebo. A consistent benefit was observed in those with or without CVD.
• The need for hospitalization by any cause was reduced by 14% in the group who received empagliflozin compared to the group who received placebo. Again, a consistent benefit was seen in those with or without CVD. Of note, the rate of hospitalization in this population of chronic kidney disease patients was very high.
• The primary outcome was dominated by reduction in the kidney outcome with empagliflozin and overall, a low event rate for CV outcome was seen. Therefore, non-significant reductions with empagliflozin were observed for CV outcomes in this trial.

Meta-analysis results

• A reduction in CV death was observed in patients with diabetes (HR 0.86, 95%CI: 0.80-0.92) or without diabetes (HR 0.88, 95%CI: 0.78-1.01) was seen, resulting in an overall reduction of CV death of 14% (HR 0.86, 95%CI: 0.81-0.92). In chronic kidney disease trials without diabetes, the confidence interval was quite wide, indicating a need for more data (there was a low number of CV death events in this population).
• Similar outcomes were seen for the combined endpoint of CV death or HF hospitalization with treatment of empagliflozin: a reduction of 23% in patients with diabetes (HR 0.77, 95%CI:0.73-0.81) and 21% in patients without diabetes (HR 0.79, 95%CI:0.72-0.87) resulting in an overall reduction of 23% (HR 0.77, 95%CI: 0.74-0.81). Again, the chronic kidney disease trials in patients without diabetes show a wide confidence interval as a results of low CV death and HF hospitalization events in this patient population.

Conclusion

The EMPA-KIDNEY trial in patients with chronic kidney disease showed that treatment with empagliflozin reduced the progression of kidney disease or CV death and reduced the need for all-cause hospitalization. Similar benefit for treatment with empagliflozin was seen regardless of CVD status. There were relatively few CV events, but results for CV death or HF hospitalization were consistent with findings from other trials

The meta-analysis of 13 major SGLT2i trials showed that in patients with diabetes reductions in CV death, and CV death and HF hospitalizations with use of SGLT2i were observed in all groups of high-risk patients. In patients without diabetes, use of SGLT2i also showed reduction in CV death, and in CV death and HF hospitalizations in patients with HF, but with less information in patients with chronic kidney disease.

• Our reporting is based on the information provided at the AHA Scientific Sessions 2022 -

The findings of the EMPA-KIDNEY trial were simultaneously published in The New England Journal of Medicine. Watch a video by David Preiss