Renal Effects of Sodium-Glucose Co-Transporter-2 Inhibitors in Patients With Heart Failure With Reduced or Preserved Ejection Fraction

Abstract

Objective:SGLT-2 inhibitors confer cardiovascular protection for patients with heart failure (HF) regardless of diabetes mellitus (DM) or chronic kidney disease (CKD) status at baseline. However, it has not been extensively studied whether SGLT-2 inhibitors exert reno-protective effects in patients with heart failure (HF), either with reduced or preserved ejection fraction (HFrEF and HFpEF, respectively). Declining of renal function is of utmost importance for patients with HF; thus, development of optimal treatment strategies to prevent or delay this progression to renal failure is required.Design and method:We sought to evaluate whether SGLT-2 inhibitors confer reno-protection in patients with HF, pooling data from relevant trials. We evaluated the following surrogate outcomes: the composite renal outcome, as defined across the 3 included trials, and the > 40% decrease in estimated glomerular filtration rate (eGFR) from baseline. Definition of composite renal endpoint is as follows: time to first occurrence of: (1) chronic dialysis; (2) renal transplantation; (3) sustained reduction of > 40% in estimated GFR; or (4) sustained estimated GFR of less than 15 ml per minute per 1.73 m2.Results:We pooled data from 3 randomized, controlled trials for a total of 14,462 enrolled subjects with HFrEF or HFpEF, assigned either to SGLT-2 inhibitor treatment or placebo. Overall risk of bias was evaluated as low across all trials. SGLT-2 inhibitor treatment resulted in a non-significant decrease in the risk for the primary composite outcome by 27% (RR = 0.73, 95% CI; 0.50–1.08 I2 = 66%, p = 0.11). In addition, SGLT-2 inhibitor treatment led to a non-significant decrease in the risk for > 40% decrease in eGFR from baseline, compared to placebo (RR = 0.70, 95% CI; 0.48–1.03, I2 = 54%, p = 0.07). No difference was identified between HFpEF and HFrEF enrolled subjects.Conclusions:SGLT-2 inhibitors provide significant cardiovascular benefits in patients with HFrEF or HFpEF; however, they do not exert significant reno-protection among patients with HF.