Abstract: SA-PO141
Can Improvements in Cardiac and Vascular Hemodynamic Markers Explain the Kidney Benefit with Empagliflozin in the EMPA-REG OUTCOME® Trial?
Session Information
- Diabetic Kidney Disease: Clinical - II
October 27, 2018 | Location: Exhibit Hall, San Diego Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Diabetic Kidney Disease
- 602 Diabetic Kidney Disease: Clinical
Authors
- Krämer, Bernhard K., University Medical Center Mannheim, University of Heidelberg, Mannheim, Germany
- Mann, Johannes F., KfH Nierenzentrum, München, Germany
- Hantel, Stefan, Boehringer Ingelheim International GmbH, Ingelheim, Germany
- Johansen, Odd Erik, Boehringer Ingelheim Norway, Asker, Norway
- von Eynatten, Maximilian, Boehringer Ingelheim International GmbH, Ingelheim, Germany
- Wanner, Christoph, Würzburg University Clinic, Würzburg, Germany
- Hauske, Sibylle Jenny, University Medical Center Mannheim, University of Heidelberg, Mannheim, Germany
Background
In the EMPA-REG OUTCOME trial (NCT01131676) empagliflozin (EMPA) added to standard of care significantly reduced clinically relevant kidney outcomes by 39% in patients with type 2 diabetes (T2D) and established cardiovascular disease (CVD). As EMPA can reduce arterial stiffness and improve vascular compliance, these effects could be potential mediators of the kidney protective effects observed. We assessed whether the effect of EMPA on indices of arterial stiffness and vascular compliance could be related to kidney outcomes.
Methods
Patients were randomized (1:1:1) to EMPA 10 mg, EMPA 25 mg, or placebo (PBO); this post-hoc analysis compared the pooled EMPA group vs PBO. We calculated change from baseline to week 12 in indices of arterial stiffness (pulse pressure), vascular resistance (mean arterial pressure), and cardiac workload (double product). Subgroups for these indices (depicted as changes above or below the median) were used to assess potential effects on incident or worsening nephropathy (composite of progression to macroalbuminuria, doubling of serum creatinine, initiation of renal replacement therapy, or renal death) and all outcome events occurring after week 12 were included in this analysis.
Results
A total of 7020 patients were randomized and treated with ≥1 study drug dose. As previously reported, EMPA significantly reduced cardiac and vascular hemodynamic markers vs PBO at week 12. However, the reduction in risk of incident or worsening nephropathy with EMPA was consistent between the three subgroups for indices, regardless of magnitude of their respective changes (Figure).
Conclusion
In patients with T2D and established CVD, empagliflozin produced a consistent benefit on kidney outcomes between subgroups for indices of arterial stiffness, vascular resistance, and cardiac workload.
Funding
- Commercial Support – Boehringer Ingelheim & Eli Lilly and Company Diabetes Alliance