Impact of eplerenone on cardiovascular outcomes in heart failure patients with hypokalaemia. (20th November 2016)

• Record Type: Journal Article
• Authors: Rossignol, Patrick; Girerd, Nicolas; Bakris, George; Vardeny, Orly; Claggett, Brian; McMurray, John J.V.; Swedberg, Karl; Krum, Henry; van Veldhuisen, Dirk J.; Shi, Harry; Spanyers, Sean; Vincent, John; Fay, Renaud; Lamiral, Zohra; Solomon, Scott D.; Zannad, Faiez; Pitt, Bertram
• Is Part Of: European journal of heart failure. Volume 19:Number 6(2017)
• Page Start: 792
• Page End: 799
• Publication Date: 2016-11-20
• Subjects: Eplerenone -- Heart failure -- Potassium -- Prognosis; Heart failure -- Periodicals; Heart Failure -- Periodicals; Insuffisance cardiaque -- Périodiques; Heart failure; Periodicals; 616.129005
• DOI: 10.1002/ejhf.688
• Languages: English
• ISSNs: 1388-9842

Abstract

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.