Cardiorenal effects of dapagliflozin according to renal function at initiation

The DAPA-CKD (Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease) trial has previously shown that the SGLT2 inhibitor dapagliflozin reduces progression of chronic kidney disease (CKD), kidney failure and cardiovascular events in people CKD, with or without type 2 diabetes (Heerspink et al, 2020). This post hoc analysis of DAPA-CKD sought to determine whether these benefits were consistent across various stages of CKD, as defined by Kidney Disease Improving Global Outcomes (KDIGO) classification at treatment initiation. In order to stratify the DAPA-CKD cohort across three subgroups, the authors created an additional risk category – moderately high risk – based on eGFR and uACR (see Figure 1).

Among the 4304 participants, overall, the primary composite renal and cardiovascular outcome (a sustained 50% decline in eGFR, end-stage renal disease, or renal or cardiovascular death) was reduced by a relative 39% with dapagliflozin compared with placebo. The present analysis shows that these effects were consistent across all three risk groups (hazard ratios 0.65, 0.44 and 0.71 in the very high, high and moderately high risk groups, respectively). The results were also consistent across the risk groups regarding the secondary outcomes.

Results were also consistent across the risk groups in people with and without type 2 diabetes, and the relative effects of dapagliflozin on eGFR decline (an early, acute fall in eGFR which then recovered, followed by a slower decline compared with placebo) were consistent across the risk categories. Dapagliflozin consistently reduced the relative risks of all primary and secondary endpoints across all individual subgroups of eGFR and uACR. Safety outcomes were also consistent.

The authors conclude that the cardiorenal benefits of dapagliflozin are consistent across KDIGO risk categories, both in people with and without type 2 diabetes. The findings support the initiation of dapagliflozin in a wide group of people with CKD for its protective benefits.

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