Serum potassium in the PARADIGM-HF trial

Ferreira, J. P., Mogensen, U. M., Jhund, P. S. , Desai, A. S., Zile, M. R., Rossignol, P., Zannad, F., Packer, M., Solomon, S. D. and McMurray, J. J.V. (2020) Serum potassium in the PARADIGM-HF trial. European Journal of Heart Failure, 22(11), pp. 2056-2064. (doi: 10.1002/ejhf.1987) (PMID:32809261) (PMCID:PMC7756204)

Abstract

Aims: The associations between potassium level and outcomes, the effect of sacubitril–valsartan on potassium level, and whether potassium level modified the effect of sacubitril–valsartan in patients with heart failure and a reduced ejection fraction were studied in PARADIGM‐HF. Several outcomes, including cardiovascular death, sudden death, pump failure death, non‐cardiovascular death and heart failure hospitalization, were examined. Methods and results: A total of 8399 patients were randomized to either enalapril or sacubitril–valsartan. Potassium level at randomization and follow‐up was examined as a continuous and categorical variable (≤3.5, 3.6–4.0, 4.1–4.9, 5.0–5.4 and ≥5.5 mmol/L) in various statistical models. Hyperkalaemia was defined as K+ ≥5.5 mmol/L and hypokalaemia as K+ ≤3.5 mmol/L. Compared with potassium 4.1–4.9 mmol/L, both hypokalaemia [hazard ratio (HR) 2.40, 95% confidence interval (CI) 1.84–3.14] and hyperkalaemia (HR 1.42, 95% CI 1.10–1.83) were associated with a higher risk for cardiovascular death. However, potassium abnormalities were similarly associated with sudden death and pump failure death, as well as non‐cardiovascular death and heart failure hospitalization. Sacubitril–valsartan had no effect on potassium overall. The benefit of sacubitril–valsartan over enalapril was consistent across the range of baseline potassium levels. Conclusions: Although both higher and lower potassium levels were independent predictors of cardiovascular death, potassium abnormalities may mainly be markers rather than mediators of risk for death.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Ferreira, Mr Joao Pedro and Jhund, Professor Pardeep and Mogensen, Dr Ulrik and McMurray, Professor John
• Authors: Ferreira, J. P., Mogensen, U. M., Jhund, P. S., Desai, A. S., Zile, M. R., Rossignol, P., Zannad, F., Packer, M., Solomon, S. D., and McMurray, J. J.V.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
• Journal Name: European Journal of Heart Failure
• Publisher: Wiley
• ISSN: 1388-9842
• ISSN (Online): 1879-0844
• Published Online: 18 August 2020
• Copyright Holders: Copyright © 2020 The Authors
• First Published: First published in European Journal of Heart Failure 22(11): 2056-2064
• Publisher Policy: Reproduced under a Creative Commons License

Project Code	Award No	Project Name	Principal Investigator	Funder's Name	Funder Ref	Lead Dept
303944		BHF Centre of Excellence	Rhian Touyz	British Heart Foundation (BHF)	RE/18/6/34217	CAMS - Cardiovascular Science