[Renal Protection by SGLT2 Inhibitors in Patients with Heart Failure Depends on Ventricular Function: Pooled Analysis...

Area of Science:

• Cardiology
• Nephrology
• Pharmacology

Background:

• Heart failure (HF) and chronic kidney disease (CKD) frequently coexist, sharing risk factors and mechanisms.
• Sodium-glucose cotransporter-2 inhibitors (SGLT-2i) offer cardiorenal benefits, but their impact on kidney function in HF patients may vary with ejection fraction (EF).

Purpose of the Study:

• To investigate if the renal protective effects of SGLT-2 inhibitors are dependent on the ejection fraction in patients with heart failure.
• To analyze the efficacy of SGLT-2 inhibitors in reducing major adverse kidney events (MAKE) across different HF phenotypes.

Main Methods:

• A meta-analysis of five randomized controlled trials comparing SGLT-2 inhibitors with placebo in HF patients.
• Risk of bias was assessed using EPHPP. Major adverse kidney events (MAKE) were the primary outcome.
• Patients were subgrouped by EF: heart failure with reduced ejection fraction (HFrEF; ≤40%) and heart failure with preserved ejection fraction (HFpEF; >40%).

Main Results:

• The global analysis of 23,163 patients showed a non-significant trend towards reduced MAKE with SGLT-2i (RR 0.76 [0.56-1.02]).
• In HFrEF, SGLT-2i significantly decreased MAKE (RR 0.58 [0.44-0.75], I²=0%), but no renal benefit was observed in HFpEF (RR 1.01 [0.83-1.23], I²=0%).
• Stratification by EF resolved heterogeneity, indicating EF as a key modulator.

Conclusions:

• SGLT-2 inhibitors demonstrate significant renal protective effects in HFrEF but not in HFpEF.
• Ejection fraction is a critical factor influencing the renal benefits of SGLT-2 inhibitors in heart failure.
• These findings underscore the need for personalized cardiorenal syndrome management based on HF phenotype.