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Canadian Journal of Cardiology

INSULIN-LIKE GROWTH FACTOR BINDING PROTEIN-7 AS A MARKER OF CARDIAC REVERSE REMODELING WITH EMPAGLIFLOZIN: A SECONDARY ANALYSIS OF THE EMPA-HEART CARDIOLINK-6 RANDOMIZED CONTROLLED TRIAL

      Background

      Reverse cardiac remodeling is believed to contribute to the cardiovascular benefits offered by sodium-glucose transport protein 2 inhibitors (SGLT2i). Given the association between insulin-like growth factor binding protein 7 (IGFBP7) levels and cardiac remodeling, it has been postulated that IGFBP7 may serve as a predictor for individuals who may derive greater benefit from SGLT2i therapy. This exploratory sub-analysis of the EMPA-HEART CardioLink-6 trial examined the association between serum IGFBP7 levels and reverse cardiac remodeling in patients treated with empagliflozin.

      Methods and Results

      The EMPA-HEART CardioLink-6 trial randomized 97 patients with type 2 diabetes and coronary artery disease to either empagliflozin (10 mg/d) or matching placebo for 6 months. The primary outcome was change in left ventricular mass indexed to body surface area (LVMi) from baseline to 6 months as measured by cardiac magnetic resonance imaging. Serum samples collected from patients at baseline were processed for detection of IGFBP7. A linear model adjusted for baseline characteristics was used to evaluate the relationship between baseline IGFBP7, 6-month change in LVMi, and treatment arm. An adjusted multivariable linear regression model was used to evaluate the association between baseline IGFBP7 and baseline LVMi. Patients with missing covariate data were excluded which resulted in a final analysis set of 74 patients. We observed no association between baseline IGFBP7 levels and change in LVMi, nor was there any significant difference in treatment effect between empagliflozin versus placebo patients (empagliflozin 6-month change in LVMi: 0.25g/m2 (95% CI: -0.17 g/m2 to 0.67 g/m2) per 1 ng/mL higher IGFBP7 vs. placebo 6-month change in LVMi: 0.07 g/m2 (95% CI: -0.21 g/m2 to 0.35 g/m2) per 1 ng/mL higher IGFBP7; Pinteraction = 0.49). We also did not detect any association between baseline IGFBP7 and baseline LVMi (P = 0.52). Additional sensitivity analysis assessing the association between IGFBP7 as a categorical variable and 6-month change in LVMi did not reveal any significant interaction (Pinteraction=0.86).

      Conclusion

      Our results suggest that empagliflozin-mediated cardiac reverse remodeling in patients with type 2 diabetes and coronary artery disease is independent of serum IGFBP7 levels. However, given the sample size and short study duration of the EMPA-HEART CardioLink-6 trial, further investigations evaluating whether IGFBP7 levels influence the clinical efficacy of SGLT2i are warranted.