Optimising Renin-Angiotensin-Aldosterone System Inhibitor Therapy in Heart Failure and Resistant Hypertension: Challenges and Solutions

This Lorraine University organised, educational event took place on the 30th August 2016 as a part of the European Society of Cardiology (ESC) Congress in Rome, Italy

Moderator: Faiez Zannad1
Faculty: Stefan D. Anker,2 Luis M. Ruilope,3 Mikhail Kosiborod4

1. CHU Vandoeuvre-lès-Nancy, Nancy, France
2. Department of Cardiology and Pneumology, University Medical Center Göttingen, Göttingen, Denmark
3. Hospital 12 de Octubre, Madrid, Spain
4. University of Missouri-Kansas City School of Medicine, Kansas City, Missouri, USA

Disclosure: Dr Ruilope has served as speaker/advisor for Amgen, AstraZeneca, Bayer, Daiichi-Sankyo, Medtronic, Novartis, Relypsa, Servier, Sanofi, Theravance, and Vifor. Prof Kosiborod has received research grants from AstraZeneca, Gilead Sciences, Sanofi, and Genentech and served as a consultant for or on the advisory board of AstraZeneca, Amgen, Boehringer-Ingelheim, Sanofi, Eli Lilly, Novo Nordisk, Merck (Diabetes), GSK, ZS Pharma, Takeda, and Glytec. He has been on the speaker’s bureau for Amgen. Prof Zannad has received steering committee fees from Bayer, Pfizer, Novartis, Boston Scientific, Resmed, Takeda, General Electric, and Boehringer-Ingelheim, acted as a consultant for Amgen, CVRx, Quantum Genomics, Relypsa, ZS Pharma, AstraZeneca, and Janssen and is the founder of Cardiorenal and CVCT. Prof Anker has no relevant disclosures to declare.
Acknowledgements: Writing assistance was provided by Kaedy Bryson of Ashfield Healthcare Communications Ltd., supported by AstraZeneca.
Support: Organised by Lorraine University, Nancy, France; supported by an unrestricted educational grant from AstraZeneca.
Citation: EMJ. 2016;1[4]:19-26.

Meeting Summary

Renin-angiotensin-aldosterone system (RAAS) inhibitor therapy has been shown to be beneficial in patients with reduced left ventricular systolic function after an acute myocardial infarction, chronic systolic heart failure, and resistant hypertension. Although RAAS inhibitors are widely regarded as life-saving drugs, their use is often associated with changes in renal function, reducing elimination of potassium from the body. This can result in elevated concentrations of serum potassium, known as hyperkalaemia, which can in turn lead to potentially life-threatening conduction abnormalities and cardiac arrhythmias, and is associated with increased risk of death.

RAAS inhibitors are intrinsically linked to hyperkalaemia, with renin inhibitors, angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers, and mineral corticoid receptor antagonists all increasing serum potassium levels. The consequences of this side effect are treatment discontinuation or underdosing in patients with heart failure, which may contribute to a higher rate of heart failurerelated hospitalisations and deaths. However, since the benefits of RAAS inhibitors outweigh the risks of hyperkalaemia, there remains the need to overcome these challenges rather than withdraw treatment.

Treatment options currently available for reducing potassium concentrations have many limitations, including uncertain efficacy, potential safety issues, as well as the fact that many therapies are temporising, only reducing serum potassium levels for a short amount of time, rather than eliminating excess potassium from the body. The clinical need to improve hyperkalaemia treatment options has led to the emergence of two novel agents: patiromer, which has been approved in the USA, and sodium zirconium cyclosilicate (SZC) which is currently in the clinical development stage. Studies have shown that these two new agents are efficacious in terms of achieving and maintaining normal potassium levels for up to 1 year and are well tolerated.

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