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Empagliflozin in HF Patients Across Kidney Risk Categories
Quick Takes
- Patients with higher-risk KDIGO risk categories were at increased risk for adverse heart failure (HF) and renal outcomes and worsening health status over time, as compared with patients in lower-risk categories.
- Empagliflozin reduced the risk for cardiovascular death or hospitalizations for HF and slowed the rate of decline in estimated glomerular filtration rate (eGFR) in all KDIGO risk categories.
- The nonlinear nature of currently used eGFR slopes and their likelihood to be confounded by an ongoing intrarenal hemodynamic effect of the drugs limit their utility in assessing the effects of SGLT2 inhibitors.
Study Questions:
What is the effect of empagliflozin across the spectrum of chronic kidney disease in a pooled analysis of the EMPEROR-Reduced and EMPEROR-Preserved trials?
Methods:
The investigators grouped 9,718 patients into Kidney Disease Improving Global Outcomes (KDIGO) categories based on estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio into low-, moderate-, high-, and very-high risk categories, comprising 32.0%, 29.1%, 21.9%, and 17.0% of the participants, respectively. The principal heart failure (HF) outcomes for this analysis were time to cardiovascular death or HF hospitalization, total HF hospitalizations, time to first HF hospitalization, cardiovascular death, and health status assessed by Kansas City Cardiomyopathy Questionnaire (KCCQ) clinical summary score. Time-to-first event analyses of HF outcomes and major renal outcomes were performed using Cox proportional hazard models adjusting for age, ejection fraction, region, sex, and diabetes status.
Results:
In the placebo arm, when compared with lower-risk categories, patients at higher risk experienced a slower rate of decline in eGFR, but a higher risk of a composite kidney event. Empagliflozin reduced the risk of cardiovascular death or HF hospitalizations similarly in all KDIGO categories (hazard ratio [HR], 0.81; 95% confidence interval [CI], 0.66-1.01 for low-; HR, 0.63; 95% CI, 0.52-0.76 for moderate-; HR, 0.82; 95% CI, 0.68-0.98 for high-; and HR, 0.84; 95% CI, 0.71-1.01 for very-high risk groups; p for trend = 0.30). Empagliflozin reduced the rate of decline in eGFR whether it was estimated by chronic slope, total slope, or unconfounded slope. When compared with the unconfounded slope, the magnitude of the effect on chronic slope was larger, and the effect on total slope was smaller. In EMPEROR-Reduced, patients at lowest risk experienced the largest effect of empagliflozin on eGFR slope; this pattern was not observed in EMPEROR-Preserved.
Conclusions:
The authors report that the benefit of empagliflozin on major HF events was not influenced by KDIGO categories.
Perspective:
This pooled analysis reports that patients in higher-risk KDIGO risk categories were at increased risk for adverse HF and renal outcomes and worsening health status over time, as compared with patients in lower-risk categories. Furthermore, empagliflozin reduced the risk for cardiovascular death or hospitalizations for HF and slowed the rate of decline in eGFR in all KDIGO risk categories. Of note, the nonlinear nature of currently used eGFR slopes and their likelihood to be confounded by an ongoing intrarenal hemodynamic effect of the drugs limit their utility in assessing the effects of sodium-glucose co-transporter-2 (SGLT2) inhibitors and indicates need to explore measures of renal function other than eGFR.
Clinical Topics: Heart Failure and Cardiomyopathies, Acute Heart Failure
Keywords: Albumins, Cardiomyopathies, Creatinine, Glomerular Filtration Rate, Heart Failure, Hospitalization, Kidney Diseases, Renal Insufficiency, Chronic, Risk, Stroke Volume, Sodium-Glucose Transporter 2 Inhibitors
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