Study design and patient population
heart failure, death, renal death, HF
HEART FAILURE, END-STAGE KIDNEY DISEASE
The trial design, baseline patient characteristics, and the main study results from the CREDENCE trial have been published previously [In this analysis, only those study participants with available plasma for analysis of IGF-1 and IGFBP-3 at baseline were included (N = 2627). Plasma samples were collected at baseline, 1 year, and 3 years, and stored at – 80 ℃ degrees centigrade. IGF-1 was measured using an automated electrochemiluminescence immunoassay (Roche Diagnostics, Mannheim, Germany). This method is standardized against the WHO International Standard 02/254. Detection limit was 7 ng/mL and coefficient of variation for repeatability was ≤ 3.5%There were 4 main goals of this analysis. First, we determined the distribution of biomarkers at baseline. Second, we evaluated canagliflozin’s effect on biomarker concentrations from baseline to 1 year and baseline to 3 years. Third, we evaluated the association between biomarker concentrations at baseline (or their change from baseline to Year 1) and cardiovascular (CV) and kidney outcomes. Clinical endpoints examined included the primary composite endpoint of CREDENCE (a composite of end-stage kidney disease, doubling of the serum creatinine level, or renal/CV death), the renal composite endpoint (a composite of end-stage kidney disease, doubling of the serum creatinine level, or renal death), as well as the composite of heart failure (HF) hospitalization or CV death, HF hospitalization, all-cause death, and CV death. Fourth, we evaluated the effect of canagliflozin on risk as a function of concentrations of IGF-1, IGFBP-3, or their ratio.