Spironolactone and New-Onset Diabetes in Heart Failure: A Post Hoc Analysis of the TOPCAT Trial.

BACKGROUND

Evidence regarding the effect of mineralocorticoid receptor antagonist therapy on the risk of new-onset diabetes remains inconsistent.

OBJECTIVES

This study aimed to examine the effect of spironolactone on the risk of incident diabetes in patients with heart failure.

METHODS

TOPCAT (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist) was a multicenter, randomized, double-blind, placebo-controlled trial evaluating the efficacy and safety of spironolactone in patients with symptomatic heart failure and a left ventricular ejection fraction ≥45%. This post hoc analysis included participants without diabetes at baseline from the TOPCAT-Americas cohort. The association between spironolactone and new-onset diabetes was assessed using Fine-Gray competing-risks regression, with death treated as a competing event.

RESULTS

The TOPCAT-Americas cohort included 1,767 patients, of whom 788 had diabetes at baseline and were excluded. This analysis therefore included 975 participants without baseline diabetes (spironolactone, n = 494; placebo, n = 481). In Fine-Gray competing-risks analysis, spironolactone was not significantly associated with new-onset diabetes compared with placebo (unadjusted subdistribution HR [sHR]: 1.24; 95% CI: 0.63-2.45; P = 0.528; adjusted sHR: 1.26; 95% CI: 0.64-2.50; P = 0.506). Similar results were observed in Cox proportional hazards models. Findings were consistent in sensitivity analyses in the Russia/Georgia (n = 1,347) and the overall TOPCAT population without baseline diabetes (n = 2,322). Subgroup analyses suggested a nonsignificant trend toward a higher risk associated with spironolactone among participants with higher blood pressure, prediabetes, higher body mass index, or former smoking status.

CONCLUSIONS

Spironolactone did not show a significant effect on new-onset diabetes in patients with heart failure with mildly reduced ejection fraction or heart failure with preserved ejection fraction. However, wide CIs and potential heterogeneity across subgroups warrant further investigation. (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist [TOPCAT]) (NCT00094302).