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Targeting the renin–angiotensin–aldosterone system in heart failure

Nature Reviews Cardiology volume 10, pages 125–134 (2013)Cite this article

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Abstract

The renin–angiotensin–aldosterone system is a well-established therapeutic target in the treatment of heart failure (HF). Substantial advances have been made with existing agents—angiotensin-converting enzyme (ACE) inhibitors, angiotensin II-receptor blockers (ARBs), and mineralocorticoid-receptor antagonists (MRAs)—and new data continue to emerge. The indication for the use of MRAs has been broadened to include potentially all patients who have HF with reduced ejection fraction (HFrEF), and ACE inhibitors might have a novel application in patients who are at risk of left ventricular dysfunction (those with aortic valvular disease or pacing-induced heart disease). ARBs have been shown to be a beneficial alternative to ACE inhibitors in HFrEF, but their value when added to ACE inhibitors has been questioned. Upstream, direct renin blockade with aliskiren is being pursued in two large trials of HF, despite the premature halting of a third study. A substantial, unmet need remains in patients who have HF with preserved ejection fraction (HFpEF). New data on spironolactone and LCZ696 (a combined ARB and neprilysin inhibitor) show promise for these patients. Results of the TOPCAT study of spironolactone in patients with HFpEF are awaited, and LCZ696 is now being tested in a large trial in patients with HFrEF.

Key Points

  • The strategy of inhibiting the renin–angiotensin–aldosterone system (RAAS) has been remarkably successful in the treatment of heart failure with reduced ejection fraction

  • Indications for the use of mineralocorticoid-receptor antagonists have broadened to potentially all patients who have heart failure with reduced ejection fraction

  • Blockade of the RAAS upstream with aliskiren, a direct renin inhibitor, is being pursued in two large, ongoing trials, despite the premature halting of a third study

  • Heart failure with preserved ejection fraction remains a substantial and unmet need in heart failure, although results from the TOPCAT study are awaitedangiotensin–aldosterone system in heart failure>angiotensin–aldosterone system.

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Acknowledgements

The authors acknowledge the secretarial contribution of Isobel Ovens, University of Dundee, UK.

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Authors and Affiliations

  1. Division of Cardiovascular & Diabetes Medicine, MailBox 2, Ninewells Hospital and Medical School, Medical Research Institute, University of Dundee, Dundee, DD1 9SY, UK

    Chim C. Lang & Allan D. Struthers

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  1. Chim C. Lang
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  2. Allan D. Struthers
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Both authors researched data for the article, contributed substantially to discussion of its content, and wrote, reviewed, and edited the manuscript before submission.

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Correspondence to Chim C. Lang.

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Competing interests

C. C. Lang is or has been a consultant for Novartis, and has received grants or research support from Novartis and Pfizer. A. D. Struthers is or has been a consultant for Merck, Pfizer, and Roche, and has received honoraria from Menarini and Pfizer.

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Lang, C., Struthers, A. Targeting the renin–angiotensin–aldosterone system in heart failure. Nat Rev Cardiol 10, 125–134 (2013). https://doi.org/10.1038/nrcardio.2012.196

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