Plasma volume reduction may explain much of empagliflozin cardioprotective effect
medwireNews: A mediation analysis indicates that empagliflozin may provide cardioprotection largely through its ability to reduce plasma volume, with traditional cardiovascular risk markers playing little or no role.
Silvio Inzucchi (Yale University School of Medicine, New Haven, Connecticut, USA) and co-researchers found that changes in hematocrit and hemoglobin during the EMPA-REG OUTCOME trial mediated a respective 51.8% and 48.9% of the difference in cardiovascular mortality risk between the empagliflozin and placebo groups, and albumin mediated 25.5%.
Changes in variables representing other potential mediators had smaller effects, with the largest being from uric acid, at 24.6%, and fasting plasma glucose, at 16.1%. In a multivariate model, the combined changes in hematocrit, fasting plasma glucose, uric acid, and urinary albumin-to-creatinine ratio explained a total 85.2% of the difference in cardiovascular mortality risk between the groups.
This implies that the mechanisms underlying empagliflozin’s cardioprotective effects are “likely multifaceted,” write the researchers in Diabetes Care. However, changes in most traditional cardiovascular risk factors, such as blood pressure, BMI, and lipid levels, accounted for little or none of the cardioprotective effect.
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