ERA 2024 – In a post hoc analysis of EMPA-KIDNEY, treatment with empagliflozin reduced the risk of kidney disease progression or CV death in patients with CKD compared with placebo, irrespective of frailty or multimorbidity.

This summary is based on the presentation of Kaitlin Mayne, MD (Oxford, UK) at the ERA Congress 2024 – The impact of multimorbidity on the effects of empagliflozin in chronic kidney disease (CKD): exploratory analyses from the EMPA-KIDNEY trial.

Introduction and methods

Patients with multimorbidity and/or frailty may experience more side effects of medications and have reduced life expectancy, which may lead to hesitancy of prescribing disease-modifying therapies to this patient population. However, patients with multimorbidity and/or frailty have higher absolute risks for adverse outcome, which may indicate that these patients benefit the most from treatment. In EMPA-KIDNEY, treatment with empagliflozin reduced the risk of kidney disease progression or death from cardiovascular causes compared with placebo. This exploratory analyses from EMPA-KIDNEY investigated the effect of multimorbidity and/or frailty on the effects of empagliflozin in CKD.

EMPA-KIDNEY was a randomized, double-blind, placebo-controlled trial in which 6609 patients with CKD at risk of progression with or without diabetes were randomized to empagliflozin 10 mg once daily or placebo. Frailty was assessed by predicting the risk of hospitalization during follow-up. A model was used to assess for each participant the individual predicted risk of hospitalization using various baseline characteristics (including NT-proBNP, eGFR, EQ-5D questionnaire, and comorbidities such as diabetes, peripheral neuropathy, HF, ischemic heart disease and ankle swelling). The population was subsequently split intro 4 groups depending on the predicted risk of hospitalization: ≤20% (n=1988), >20 to ≤35% (n=2504), >35% to ≤45% (n=968), and >45% (n=1149). Multimorbidity was defined as the number of coexisting medical conditions at randomization excluding CKD.

The primary outcome was a composite of CV death or kidney disease progression (defined as end-stage kidney disease, a sustained eGFR decline to <10 ml/min/1.73m² or ≥ 40%, or renal death).

Main results

• The relative effects of empaliflozin versus placebo on the primary composite outcome were consistent across all frailty subgroups (HR: 0.77; 95%CI: 0.56-1.06 in the ≤20% risk group; HR: 0.65; 95%CI: 0.53-0.80 in the >20 to ≤35% risk group; HR: 0.66; 95%CI: 0.49-0.90 in the >35% to ≤45% risk group; and 0.79; 95%CI: 0.6-1.00 in the >45% risk group; P trend=0.75).
• The absolute treatment effects of empagliflozin versus placebo on the primary outcome were greater in patients who were more frail (estimated absolute events avoided per 1000 patient-years were 14 [95%CI: 9-18], 25 [95%CI: 17-33], 31 [95%CI:21-41], and 38 [95%CI: 25-50] in the ≤20, >20 to ≤35%, >35% to ≤45% , and >45% risk groups, respectively; P trend<0.001).
• For the primary composite endpoint, consistent benefit of empagliflozin versus placebo was observed in all patients, regardless of multimorbidity (HR: 0.71; 95%CI: 0.60-0.85 in the ≤1 multimorbidity group; HR: 0.85; 95%CI: 0.65-1.11 in the 2 multimorbidity group; and HR: 0.66; 95%CI: 0.51-0.85 in the ≥3 multimorbidity group; P trend=0.82).
• Empagliflozin reduced the absolute risk of the primary outcome across the multimorbidity groups (P trend=0.33).

Conclusion

In this analysis of EMPA-KIDNEY, treatment with empagliflozin reduced the relative risk of kidney disease progression or CV death in patients with CKD irrespective of frailty or baseline multimorbidity. The absolute effects however were greater in patients who had the highest risk of hospitalization. “We feel like guidelines should encourage SGLT2 inhibitors use in CKD, irrespective of frailty or multimorbidity as such patients may have most to gain”, said Kaitlin Mayne.

- Our reporting is based on the information provided at the ERA Congress 2024 -