Physicians' Academy for Cardiovascular Education

Efficacy of two SGLT2i on CV and kidney outcomes in HFrEF according to kidney function

Literature - Jhund PS et al. and Zannad F et al., - Circulation. 2021

Prespecified subgroup analyses from DAPA-HF (Dapagliflozin and Prevention of Adverse-outcomes in Heart Failure) and EMPEROR-Reduced evaluated the effects of SGLT2 inhibitors dapagliflozin and empagliflozin on CV and kidney outcomes according to baseline kidney function in patients with HFrEF.

DAPA-HF demonstrated that dapagliflozin reduced incidence of CV death or worsening HF in patients with HFrEF, with or without T2DM. DAPA-HF enrolled patients with eGFR ≥30 mL/min/1.73 m² and 41% had eGFR <60 mL/min/1.73 m² at baseline. The current analysis showed that the efficacy of dapagliflozin in preventing CV death or worsening HF did not differ by eGFR category (<60 mL/min/1.73 m² vs. ≥60 mL/min/1.73 m², P for interaction =0.54). Effects of dapagliflozin on reducing CV death, HF hospitalizations, urgent HF visits, total HF hospitalizations and all-cause death were also similar in both eGFR groups. The prespecified composite renal outcome was defined as a ≥50% sustained decline eGFR, end-stage renal disease, or renal death. Although incidence rates were numerically lower in patients on dapagliflozin, the difference between dapagliflozin and placebo on the composite renal outcome was not significant (HR 0.71, 95%CI 0.44-1.16, P=0.17). However, rate of decline in eGFR between day 14 and 720 was less in the dapagliflozin group compared to the placebo group (dapagliflozin: -1.09 mL/min/1.73 m², 95%CI -1.40 to -0.77; placebo: -2.85 mL/min/1.73 m², 95%CI -3.17 to -2.53; P for difference in slopes <0.001). The slowing of eGFR decline was observed in those with and without T2DM and in those with and without low eGFR. Dapagliflozin also reduced risk of doubling serum creatinine relative to the last laboratory measure, compared to placebo (HR 0.56, 95%CI 0.39-0.82, P=0.003). Furthermore, SAE’s occurred significantly less frequently in the dapagliflozin group (n=38, 1.6%) compared to the placebo group (n=65, 2.6%, P=0.009).

EMPEROR-Reduced showed that empagliflozin reduced the composite outcome of CV death or hospitalization for HF in patients with HFrEF with or without T2DM, compared with placebo. Empagliflozin also reduced the risk for adverse renal outcomes and slowed the rate of decline in eGFR. Important to note is that EMPEROR-Reduced enrolled patients with an eGFR as low as 20 mL/min/1.73 m² and 53% of the participants had prevalent CKD (eGFR <60 mL/min/1.73 m² or UACR >300 mg/g) at baseline. The current analysis evaluated the effect of empagliflozin on CV and kidney outcomes in patients with and without CKD and across the spectrum of kidney function. Empagliflozin reduced the primary efficacy outcome of time-to-first CV death or HF hospitalization and key secondary outcome of total HF hospitalizations in patients with and without CKD and irrespective of eGFR or UACR at baseline. The effects of empagliflozin on the composite kidney outcome of sustained profound decline in eGFR, chronic dialysis, or kidney transplant did not differ between patients with and without CKD (with CKD: HR 0.53, 95%CI, 0.31–0.91; without CKD: HR 0.46; 95%CI, 0.22–0.99; P for interaction=0.78). kidney outcomes were consistent across the spectrum of kidney function, irrespective eGFR or albuminuria at baseline. Empagliflozin reduced the slope of decline in eGFR by 1.11 (95%CI 0.23-1.98) mL/min/1.73m² per year in patients with CKD and by 2.41 (95%CI 1.49-3.32) mL/min/1.73m² per year in those without CKD (P for interaction = 0.045). There was no significant difference in AEs in patients receiving empagliflozin, as compared to those receiving placebo, across categories of kidney function.

Find the article on efficacy of dapagliflozin on renal function and outcomes by Jhund et al. online at Circulation Find the article on cardiac and kidney benefits of empagliflozin by Zannad et al. online at Circulation

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