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Dapagliflozin's Overwhelming Benefit in CKD

— SGLT2 inhibitor shows fewer renal events, prolonged overall survival

MedpageToday

In chronic kidney disease (CKD), dapagliflozin (Farxiga) reduced renal events and substantially improved overall survival, regardless of diabetes status, the DAPA-CKD trial showed. The findings were presented at the recent , as well as in a secondary analysis at the recent Kidney Week 2020 meeting.

Study investigator , of George Institute for Global Health in Sydney, Australia, describes the key results and takeaways from the study.

Following is a transcript of his remarks:

So SGLT-2 inhibitors, as we all know, were developed as drugs to improve glycemic control in patients with type 2 diabetes. In the CREDENCE study, canagliflozin improved both cardiovascular and kidney outcomes in patients who had the combination of type 2 diabetes and chronic kidney disease. We did not know whether these benefits extended to patients who had chronic kidney disease but who did not have type 2 diabetes. And the DAPA-CKD study assessed the clinical outcome benefits of dapagliflozin in patients who had chronic kidney disease but, due to a broader range of underlying etiology, not just diabetic kidney disease.

Now our primary outcome in this study was the composite of a greater than or equal to 50% decline in eGFR. And that needed to be confirmed with a followup blood sample. The development of end stage kidney disease -- that's an eGFR of persistently greater than 15, or the need for dialysis or kidney transplantation, and deaths due to either renal or cardiovascular causes. Our secondary outcomes were the composite of a 50% decline in eGFRs with end-stage kidney disease and renal death. So that's the primary outcome without the cardiovascular death component. So this is a pure renal composite. Our second secondary endpoint was a cardiovascular composite of cardiovascular death and hospitalization for heart failure. And our third secondary outcome was all cause mortality.

Now, first let's look at the outcomes by diabetes status and we've already presented and published these data, showing the beneficial effects of dapagliflozin on the primary outcome at the top here and on all three of the secondary outcomes. So you see here, the secondary outcomes added in by diabetes status. For example, looking at the all cause mortality outcome at the bottom here, you can see that the reductions in risk were nominally statistically significant whether or not the patient had type 2 diabetes at baseline.

So here we see the baseline characteristics by underlying cause of chronic kidney disease across the top here, then subdivided by treatment allocation in the study. So the patients with diabetic nephropathy and ischemic nephropathy tended to be older and tended to be heavier than the patients with the glomerulonephritides and chronic kidney disease and other/unknown cause.

Those groups with nondiabetic kidney disease tended to have lower GFRs and lower levels of albuminuria. And the patients with glomerulonephritis tended to have lower blood pressures, perhaps this is better treated hypertension than those in the other groups. Importantly, there's a good balance here between those patients randomized to dapagliflozin or placebo within all these different etiological groupings.

So here's our primary outcome, according to the underlying cause of chronic kidney disease. This is the overall result at the top that you've already seen. Here is the primary outcome divided by disease etiology. And you can see here a consistent effect is the P for interaction, which is not statistically significant. These results are very similar as you can see. And we're going to now show the first secondary outcome. Remember that's the primary without cardiovascular death. So things hardly change here, again a consistent effect regardless of the underlying disease etiology.

So here's our second secondary outcome. This is the composite of cardiovascular death or hospitalization for heart failure, cardiovascular composite. There's a little bit more variability here. There's wider confidence intervals, as you can see, and there's lower numbers of events here. But again, overall a consistent effect with no statistical difference between these results. And then our third secondary outcome, all cause mortality, overall effect, and then data by underlying disease etiology again, consistent P-value for interaction, not statistically significant.

So in conclusion, as we've already seen from this study in patients with chronic kidney disease, with them without type 2 diabetes, dapagliflozin reduced the risk of kidney failure, reduced the risk of death from cardiovascular causes or hospitalization for heart failure and prolonged survival. In this pre-specified analysis, we've shown that these renal cardiovascular mortality benefits, are present regardless of the underlying cause of chronic kidney disease, and regardless of the presence or absence of type 2 diabetes. And dapagliflozin was well tolerated with a safety profile that is consistent with that seen in other patient populations.

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    Greg Laub is the Senior Director of Video and currently leads the video and podcast production teams.