Empagliflozin reduces risk of kidney disease progression and CV events in patients with CKD

Empagliflozin significantly reduced the risk of the composite outcome of progression of kidney disease or death from cardiovascular (CV) causes by 28% in the phase 3 EMPA-KIDNEY trial. The results also showed a 14% decrease in hospitalisation due to any cause.

Associate Prof. David Preiss (University of Oxford, UK) presented data from the EMPA-KIDNEY trial (NCT03594110), and a meta-analysis on the effect of sodium-glucose cotransporter-2 (SGLT2) inhibition [1]. The EMPA-KIDNEY trial randomised 6,609 patients with chronic kidney disease at risk of progression to either 10 mg of empagliflozin once daily or placebo [1,2]. The trial included patients with an estimated glomerular filtration rate (eGFR) ≥20 and <45 mL/minute/1.73 m² of body-surface area. The primary composite outcome was CV death or kidney disease progression. The median follow-up was 2 years. At baseline, the mean age was 64 years, ~33% were women, and the mean eGFR was 37 mL/min/1.73m². “We aimed to recruit many patients without diabetes,” Dr Preiss elaborated, resulting in more than half of randomised participants not having diabetes.

A primary outcome event happened significantly less often in participants treated with empagliflozin compared with placebo: 13.1% versus 16.9% (P<0.001). This corresponded to a hazard ratio reduction of 0.72 (95% CI 0.64–0.82). Similar differences were found when stratifying according to prior vascular disease. Dr Preiss emphasised that the effect was mainly driven by the renal component of the primary outcome. “The number of cardiovascular deaths (128 of 990 events) was smaller than expected,” he detailed. All-cause hospitalisation was significantly reduced by 14% (95% CI 0.78–0.95) by treatment with empagliflozin, an effect that was consistent across subgroups including diabetes status and eGFR. Analyses of recurrent CV events, such as HF hospitalisation, and major adverse CV events, all showed clear but non-significant trends for a reduction with empagliflozin. According to Dr Preiss, the lack of significance was likely due to underpowering of the study regarding CV outcomes.

To shed further light on the cardiovascular efficacy of SGLT2 inhibitors, Dr Preiss also revealed results from a collaborative meta-analysis of 13 large SGLT2 inhibitor trials [1,3]. “Over 90,000 participants were available for these analyses, 80% had diabetes,” Dr Preiss stated, underlining that this still meant over 19,000 patients did not have diabetes. CV outcome analysis demonstrated an overall significant reduction of CV death or HF hospitalisation with SGLT2 inhibition by 23% (95% CI 0.74–0.81). Stratification into patients with and without diabetes led to consistent results in both subgroups. “For this analysis, we had rather limited information on the patient group with chronic kidney disease but without diabetes,” he added. As for CV death alone, the SGLT2 inhibitors resulted in a decrease of 14% overall, with relative risks of 0.86 (95% CI 0.80–0.92) for diabetic and 0.88 (95% CI 0.78–1.01) for non-diabetic patients.

“Our results suggest that SGLT2 inhibitors such as empagliflozin should be offered to all adults with chronic kidney disease at risk of kidney disease progression and CV complications, regardless of whether they have type 2 diabetes,” Dr Preiss expressed.

Prof. Naveed Sattar (University of Glasgow, UK), a discussant of the trial, added that these excellent results should encourage us to investigate SGLT2 inhibitors in patients with other conditions, including pre-diabetic patients, kidney transplant recipients, patients with non-alcoholic fatty liver disease (NAFLD), and patients with a recent myocardial infarction (post-MI).

1. 
   
   1. Preiss D. Empagliflozin and cardiovascular outcomes in patients with chronic kidney disease: the EMPA-KIDNEY trial. LBS.05, AHA Scientific Sessions 2022, 05–07 November, Chicago, USA.
   2. Herrington WG, et al. N Engl J Med, Nov 4, 2022. DOI: 10.1056/nejmoa2204233.
   3. The Nuffield Department of Population Health Renal Studies Group and the SGLT2 inhibitor Meta-Analysis Cardio-Renal Trialists' Consortium. Lancet. 2022;400(10365):1788–1801.

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Posted on 11 January 202317 May 2024