Format

Send to

Choose Destination
Eur J Heart Fail. 2017 Jun;19(6):792-799. doi: 10.1002/ejhf.688. Epub 2016 Nov 20.

Impact of eplerenone on cardiovascular outcomes in heart failure patients with hypokalaemia.

Author information

1
Inserm, Centre d'Investigations Cliniques-Plurithématique 14-33, and Inserm U1116, Nancy, France.
2
CHU Nancy, Pôle de Cardiologie, Vandoeuvre lès Nancy, France.
3
Université de Lorraine, France.
4
F-CRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists), Nancy, France.
5
ASH Comprehensive Hypertension Center, The University of Chicago Medicine, Chicago, IL, USA.
6
University of Wisconsin School of Pharmacy, Madison, WI, USA.
7
Brigham and Women's Hospital, Boston, MA, USA.
8
The British Heart Foundation Cardiovascular Research Centre, University of Glasgow, Glasgow, UK.
9
Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
10
Monash University, Melbourne, VIC, Australia.
11
University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
12
Pfizer, NY, USA.
13
University of Michigan School of Medicine, Ann Arbor, MI, USA.

Abstract

AIMS:

Although hypokalaemia is common among patients with heart failure (HF), the prognostic significance of baseline hypokalaemia and hypokalaemia during follow-up in HF patients receiving a mineralocorticoid receptor antagonist (MRA) remains uncertain.

METHODS AND RESULTS:

Results of the EMPHASIS-HF trial in patients (n = 2737) with HF and reduced EF with mild symptoms, randomized to eplerenone or placebo, were analysed with regard to the presence or occurrence of hypokalaemia (serum K+ <4.0 mmol/L) and the risk of cardiovascular death or hospitalization for HF (primary endpoint). Median follow-up was 21 months. Baseline hypokalaemia and hypokalaemia during follow-up were common occurrences (19.6% and 40.6%, respectively). Hypokalaemia during follow-up was associated with worse outcomes in multivariable analyses [hazard ratio (HR) 1.26, 95% confidence interval (CI) 1.05-1.52, P = 0.01] without evidence of interaction with eplerenone. In contrast, baseline hypokalaemia was associated with outcomes in the placebo group (HR 1.37, 95% CI 1.05-1.79, P = 0.02) but not in the eplerenone group (HR 0.87, 95% CI 0.62-1.23, P = 0.44; P for interaction = 0.04). Concurrently, eplerenone was found to be more protective in patients with baseline hypokalaemia vs. patients without baseline hypokalaemia compared with placebo (HR 0.44, 95% 0.30-0.64, P < 0.0001 vs. 0.69, 95% CI 0.57-0.83, P = 0.0001; P for interaction = 0.04). In patients without baseline hypokalaemia, eplerenone use decreased the rate of hypokalaemia during follow-up (HR 0.69, 95% CI 0.59-0.80, P < 0.001). A potassium level >4.0 mmol/L at 1 month after randomization mediated 26.0% (0.6-51.4%) of the eplerenone treatment effect (P = 0.04).

CONCLUSION:

In HF patients receiving optimal therapy but not treated with eplerenone, baseline hypokalaemia was associated with worse outcomes. Conversely, hypokalaemia amplified the treatment effect of eplerenone.

KEYWORDS:

Eplerenone; Heart failure; Potassium; Prognosis

PMID:
27868385
DOI:
10.1002/ejhf.688
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Wiley
Loading ...
Support Center