Risk factors for heart failure in patients with type 2 diabetes mellitus and stage 4 chronic kidney disease treated with bardoxolone methyl.
نویسندگان
چکیده
BACKGROUND A phase 3 randomized clinical trial was designed to test whether bardoxolone methyl, a nuclear factor erythroid-2-related factor 2 (Nrf2) activator, slows progression to end-stage renal disease in patients with stage 4 chronic kidney disease and type 2 diabetes mellitus. The trial was terminated because of an increase in heart failure in the bardoxolone methyl group; many of the events were clinically associated with fluid retention. METHODS AND RESULTS We randomized 2,185 patients with type 2 diabetes mellitus (T2DM) and stage 4 chronic kidney disease (CKD) (estimated glomerular filtration rate 15 to <30 mL min(-1) 1.73 m(-2)) to once-daily bardoxolone methyl (20 mg) or placebo. We used classification and regression tree analysis to identify baseline factors predictive of heart failure or fluid overload events. Elevated baseline B-type natriuretic peptide and previous hospitalization for heart failure were identified as predictors of heart failure events; bardoxolone methyl increased the risk of heart failure by 60% in patients with these risk factors. For patients without these baseline characteristics, the risk for heart failure events among bardoxolone methyl- and placebo-treated patients was similar (2%). The same risk factors were also identified as predictors of fluid overload and appeared to be related to other serious adverse events. CONCLUSIONS Bardoxolone methyl contributed to events related to heart failure and/or fluid overload in a subpopulation of susceptible patients with an increased risk for heart failure at baseline. Careful selection of participants and vigilant monitoring of the study drug will be required in any future trials of bardoxolone methyl to mitigate the risk of heart failure and other serious adverse events.
منابع مشابه
Is B-type natriuretic peptide a risk factor for heart failure in patients treated with bardoxolone methyl?
Letter to the Editor, comment on article entitled "Risk Factors for Heart Failure in Patients With Type 2 Diabetes Mellitus and Stage 4 Chronic Kidney Disease Treated With Bardoxolone Methyl" by Chin et al in the Journal of Cardiac Failure. Disciplines Medicine and Health Sciences Publication Details Camer, D. & Huang, X. (2015). Is B-type natriuretic peptide a risk factor for heart failure in ...
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ورودعنوان ژورنال:
- Journal of cardiac failure
دوره 20 12 شماره
صفحات -
تاریخ انتشار 2014