SGLT2i reduces risk of kidney and CV outcomes across subgroups of baseline UACR

Efficacy and safety of dapagliflozin on kidney and cardiovascular outcomes by baseline albuminuria: a secondary analysis of the DAPA-CKD trial

Presented at the EASD 2021 by: Prof. Hiddo Lambers Heerspink, MD - Groningen, The Netherlands

Introduction and methods

The DAPA-CKD trial previously showed that the SGLT2 inhibitor dapagliflozin reduced the risk of kidney failure, HF hospitalizations or CV death and all-cause mortality in patients with CKD, with or without T2DM. This prespecified secondary analysis assessed the efficacy and safety of dapagliflozin on kidney and CV outcomes according to baseline albuminuria.

In DAPA-CKD, patients with CKD (UACR 200-5000 mg/g; eGFR 25-75 mL/min/1.73m²) were randomized to dapagliflozin 10 mg/d or placebo. The primary endpoint was a composite of sustained ≥50% decline in eGFR, onset of end-stage kidney disease, or death from a kidney or CV causes. Secondary outcomes included a kidney-specific outcome (primary outcome excluding CV death), CV death or HF hospitalization, and all-cause mortality.

The current analysis assessed the relative and absolute effects of dapagliflozin vs. placebo for primary and secondary outcomes stratified by UACR at baseline (≤1000 mg/g, >1000 to ≤3500 mg/g, >3500 mg/g).

Main results

• The relative risk reduction with dapagliflozin vs placebo on the primary endpoint was consistent across subgroups of UACR (P for interaction=0.93). The event rate for the primary endpoint substantially increased with increasing UACR subgroup. The absolute risk reduction for the primary endpoint with dapagliflozin was significantly greater in subgroups with higher UACR (3.5% [95%CI 1.6-5.4%] for UACR ≤1000 mg/g, 6.9% [95%CI 3.6-10.1%] for UACR>1000 to ≤3500 mg/g, and 13.8% [95%CI 3.0-24.5%] for UACR >3500 mg/g, P for interaction =0.02).
• The relative risk reduction with dapagliflozin vs placebo on the primary endpoint was consistent across subgroups of UACR in patients with and without T2DM (P for interaction =0.93 and 0.42, respectively).
• The relative risk reduction with dapagliflozin was consistent across UACR subgroups for all secondary outcomes (all P for interaction >0.59). The absolute risk reduction for the kidney-specific outcome with dapagliflozin was significantly greater in subgroups with higher UACR (P for interaction=0.002).
• The acute eGFR slope (baseline to week 2) showed that dapagliflozin reduced the eGFR by 2 to 3 mL/min/1.73m² in each UACR subgroup. However, the total eGFR slope (baseline to end-of treatment) showed that dapagliflozin, irrespective of baseline UACR subgroup, slowed the decline of eGFR, compared to placebo.
• The proportion of patients reporting serious adverse events or with adverse events leading to study drug discontinuation was similar between the dapagliflozin group and placebo group and consistent across UACR subgroups.

Conclusion

This prespecified secondary analysis of the DAPA-CKD trial showed that the efficacy and safety of dapagliflozin on kidney and CV outcomes was consistent across subgroups of baseline UACR in patients with CKD with and without T2DM.

-Our reporting is based on the information provided at the EASD Virtual Meeting–