Association of Empagliflozin Treatment With Albuminuria Levels in Patients With Heart Failure A Secondary Analysis of EMPEROR-Pooled

Autores da FMUP

• João Pedro Melo Marques Pinho Ferreira

  Autor

Participantes de fora da FMUP

• Zannad, F
• Butler, J
• Filippatos, G
• Pocock, SJ
• Brueckmann, M
• Steubl, D
• Schueler, E
• Anker, SD
• Packer, M

Unidades de investigação

• Cirurgia e Fisiologia

• Laboratório Associado RISE- Rede de Investigação em Saúde

  

  Investigador

  Fernando Carlos De Landér Schmitt

Abstract

IMPORTANCE Albuminuria, routinely assessed as spot urine albumin-to-creatinine ratio (UACR), indicates structural damage of the glomerular filtration barrier and is associated with poor kidney and cardiovascular outcomes. Sodium-glucose cotransporter-2 (SGLT2) inhibitors have been found to reduce UACR in patients with type 2 diabetes, but its use in patients with heart failure (HF) is less well studied. OBJECTIVE To analyze the association of empagliflozin with study outcomes across baseline levels of albuminuria and change in albuminuria in patients with HF across a wide range of ejection fraction levels. DESIGN, SETTING, AND PARTICIPANTS This post hoc analysis included all patients with HF from the EMPEROR-Pooled analysis using combined individual patient data from the international multicenter randomized double-blind parallel-group, placebo-controlled EMPEROR-Reduced and EMPEROR-Preserved trials. Participants in the original trials were excluded from this analysis if they were missing baseline UACR data. EMPEROR-Preserved was conducted from March 27, 2017, to April 26, 2021, and EMPEROR-Reduced was conducted from April 6, 2017, to May 28, 2020. Data were analyzed from January to June 2022. INTERVENTIONS Randomization to empagliflozin or placebo. MAIN OUTCOMES AND MEASURES New-onset macroalbuminuria and regression to normoalbuminuria and microalbuminuria. RESULTS A total of 9673 patientswere included (mean [SD] age, 69.9 [10.4] years; 3551 [36.7%] female and 6122 [63.3%] male). Of these, 5552 patients had normoalbuminuria (UACR <30 mg/g) and 1025 had macroalbuminuria (UACR >300mg/g). Compared with normoalbuminuria, macroalbuminuriawas associated with younger age, races other than White, obesity, male sex, site region other than Europe, higher levels of N-terminal pro-hormone brain natriuretic peptide and high-sensitivity troponin T, higher blood pressure, higher New York Heart Association class, greater HF duration, more frequent previous HF hospitalizations, diabetes, hypertension, lower eGFR, and less frequent use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers and mineralocorticoid receptor antagonists. An increase in eventswas observed in individuals with higher UACR levels. The association of empagliflozin with cardiovascular mortality orHF hospitalizationwas consistent across UACR categories (hazard ratio [HR], 0.80; 95% CI, 0.69-0.92 for normoalbuminuria; HR, 0.74; 95% CI, 0.63-0.86 for microalbuminuria; HR, 0.78; 95% CI, 0.63-0.98 for macroalbuminuria; interaction P trend =.71). Treatment with empagliflozinwas associated with lower incidence of new macroalbuminuria (HR, 0.81; 95% CI, 0.70-0.94; P =.005) and an increase in rate of remission to sustained normoalbuminuria or microalbuminuria (HR, 1.31; 95% CI, 1.07-1.59; P =.009) but not with a reduction in UACR in the overall population; however, UACRwas reduced in patients with diabetes, who had higher UACR levels than patients without diabetes (geometric mean for diabetes at baseline, 0.91; 95% CI, 0.85-0.98 and for no diabetes at baseline, 1.08; 95% CI, 1.01-1.16; interaction P =.008). CONCLUSIONS AND RELEVANCE In this post hoc analysis of a randomized clinical trial, compared with placebo, empagliflozin was associated with reduced HF hospitalizations or cardiovascular death irrespective of albuminuria levels at baseline, reduced progression to macroalbuminuria, and reversion of macroalbuminuria.

Keywords

• Aged; Albuminuria; Diabetes Mellitus, Type 2; Female; Glomerular Filtration Rate; Heart Failure; Humans; Male; albumin; amino terminal pro brain natriuretic peptide; angiotensin receptor antagonist; dipeptidyl carboxypeptidase inhibitor; empagliflozin; enkephalinase inhibitor; hemoglobin; insulin; loop diuretic agent; mineralocorticoid antagonist; placebo; potassium; thiazide diuretic agent; troponin T; empagliflozin; acute kidney failure; adult; aged; albumin blood level; albumin to creatinine ratio; all cause mortality; Article; atrial fibrillation; body mass; cardiac resynchronization therapy; cardiovascular mortality; controlled study; diabetes mellitus; diastolic blood pressure; disease association; disease duration; double blind procedure; estimated glomerular filtration rate; female; heart atrium flutter; heart failure; heart left ventricle ejection fraction; heart muscle ischemia; heart rate; hemoglobin blood level; human; hypertension; incidence; kidney transplantation; macroa