Heart Failure
Mineralocorticoid Receptor Antagonist Use in Hospitalized Patients With Heart Failure, Reduced Ejection Fraction, and Diabetes Mellitus (from the EVEREST Trial)

https://doi.org/10.1016/j.amjcard.2014.05.064Get rights and content

Despite the well-established benefits of mineralocorticoid receptor agonists (MRAs) in heart failure with reduced ejection fraction, safety concerns remain in patients with concomitant diabetes mellitus (DM) because of common renal and electrolyte abnormalities in this population. We analyzed all-cause mortality and composite cardiovascular mortality and HF hospitalization over a median 9.9 months among 1,998 patients in the placebo arm of the Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study With Tolvaptan (EVEREST) trial by DM status and discharge MRA use. Of the 750 patients with DM, 59.2% were receiving MRAs compared with 62.5% in the non-DM patients. DM patients not receiving MRAs were older, more likely to be men, with an ischemic heart failure etiology and slightly worse renal function compared with those receiving MRAs. After adjustment for baseline risk factors, among DM patients, MRA use was not associated with either mortality (hazard ratio [HR] 0.93; 95% confidence interval [CI] 0.75 to 1.15) or the composite end point (HR 0.94; 95% CI 0.80 to 1.10). Similar findings were seen in non-DM patients (mortality [HR 1.01; 95% CI 0.84 to 1.22] or the composite end point [HR 0.98; 95% CI 0.85 to 1.13] [p >0.43 for DM interaction]). In conclusion, in-hospital initiation of MRA therapy was low (15% to 20%), and overall discharge MRA use was only 60% (with regional variation), regardless of DM status. There does not appear to be clear, clinically significant in-hospital hemodynamic or even renal differences between those on and off MRA. Discharge MRA use was not associated with postdischarge end points in patients hospitalized for worsening heart failure with reduced ejection fraction and co-morbid DM. DM does not appear to influence the effectiveness of MRA therapy.

Section snippets

Methods

The study design16 and primary results17, 18 of the EVEREST trial have been previously described. In brief, EVEREST was a prospective, international, randomized, double-blind, placebo-controlled trial designed to explore the short- and long-term impact of tolvaptan, a vasopressin-2 receptor antagonist, when added to standard therapy, in patients hospitalized for worsening HF with an EF ≤40% and presenting with an evidence of fluid overload. Participants were randomized within 48 hours of

Results

Of the 2,061 patients assigned to the placebo arm in the EVEREST trial, 3.3% (n = 63) of patients died during hospitalization or had missing discharge MRA data. Of those discharged alive with known MRA status, 62.3% (n = 1,245) received an MRA at discharge. Baseline DM was present in 37.5% (n = 750) of patients, and among these, 59.2% (n = 444) were discharged on MRA therapy, compared with 64.2% (n = 801) in patients without DM (Figure 1). Most of these patients had been prescribed an MRA at

Discussion

In a large, international cohort of contemporary patients hospitalized with worsening HFrEF, in-hospital initiation of MRA therapy was low (15% to 20%), and overall discharge MRA use was only 60% (with regional variation), regardless of DM status. Patients with DM who were not prescribed MRAs at discharge appeared to have less severe and symptomatic HF compared with those prescribed MRAs at discharge, as evidenced by a higher left ventricular EF, better NYHA functional class, and lower

Disclosures

Dr. Subacius conducted all final analyses for this article with funding from the Center for Cardiovascular Innovation (Northwestern University Feinberg School of Medicine, Chicago, IL). The authors had full access to the data, take responsibility for its integrity, and had complete control and authority over manuscript preparation and the decision to publish. Dr. Chioncel has received research support from Abbott, Servier, Vifor, and served as member on the Steering Committee of studies

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    Otsuka Inc. (Rockville, MD) provided financial and material support for the EVEREST trial. Database management was performed by the sponsor.

    See page 749 for disclosure information.

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