1. In this post-hoc analysis of a randomized controlled trial, empagliflozin use in patients with heart failure (HF) was associated with decreased rate of new onset macroalbuminuria and increased rate of sustained remission from macroalbuminuria, which is an important variable in assessing severity of chronic kidney disease.
Evidence Rating Level: 1 (Excellent)
Albuminuria, defined as spot urine albumin-to-creatinine ratio (UACR) is an important indicator of structural damage of glomerular filtration barrier, and is key in assessing chronic kidney disease. Previous studies have shown benefits of angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs) in reducing albuminuria. Furthermore, sodium glucose cotransporter-2 inhibitors have been shown to reduce the progression of albuminuria to macroalbuminuria in patients with diabetes and CKD, with and without diabetes. Research has shown that macroalbuminuria in patients with heart failure is associated with increased risk of hospitalizations and mortality. Using data from the Empagliflozin Outcome Trial in Patients With Chronic Heart Failure with Reduced Ejection Fraction (EMPEROR-Reduced) and Empagliflozin in Heart Failure with a Preserved Ejection Fraction (EMPEROR-Preserved), known as EMPEROR-Pooled, the association of empagliflozin with albuminuria was studied. EMPEROR-Pooled was an international multicenter randomized double-blinded, placebo-controlled trial that enrolled patients with chronic heart failure. Patients were randomized in a double-blind manner to receive placebo or empagliflozin, and albuminuria was assessed using UACR at weeks 4, 12, 32, 52, and every 24 weeks afterward. The primary outcome was both cardiovascular death or heart failure (HF) hospitalization. 9,673 patients were included in this study; 5552 patients had normoalbuminuria (UACR < 30 mg/g), and 1025 patients had macroalbuminuria (UACR > 300 mg/g). Treatment with empagliflozin was associated with a reduction in the incidence of new macroalbuminuria (P=.005), which was consistent across subgroups. Furthermore, among the patients with existing macroalbuminuria, empagliflozin was associated with an increased rate of remission to normoalbuminuria or microalbuminuria (P=.009). However, empagliflozin was not significantly associated with relative changes in UACR over time in the overall population. A major limitation of this study was that the physiological mechanism through which empagliflozin reduces albuminuria could not be determined, which may cause hesitance among physicians. Overall, the findings from this post-hoc analysis suggest that empagliflozin was associated with a decreased rate of new onset macroalbuminuria, and an increased rate of sustained remission to normoalbuminuria or microalbuminuria in patients with heart failure across all subgroups. Empagliflozin was also associated with improved cardiovascular and kidney outcomes irrespective of baseline UACR. This post-hoc analysis supports use of empagliflozin in patients with heart failure, across all types of albuminuria, and will hopefully guide future clinical practice in early use of empagliflozin to prevent progression of kidney disease.
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