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  • Review Article
  • Published:

New medical therapies for heart failure

Key Points

  • Heart failure (HF) is a major global health problem leading to premature death, substantial morbidity, low quality of life, and enormous health-care expenditure

  • Major therapeutic breakthroughs have been achieved throughout the past 4 decades with neurohormonal modulators for systolic HF

  • No medical therapy has yet been shown to reduce long-term clinical outcomes in HF with preserved ejection fraction or in acute decompensated HF

  • The first dual-acting angiotensin receptor–neprilysin inhibitor has demonstrated superior efficacy in treatment of systolic HF versus standard therapy, and several other novel drug classes are undergoing advanced clinical testing

  • Future HF trials should incorporate novel end points that comprehensively reflect the disease burden of 'real-world' HF, and include active run-in periods to identify patients vulnerable to off-target effects

Abstract

Heart failure (HF) can rightfully be called the epidemic of the 21st century. Historically, the only available medical treatment options for HF have been diuretics and digoxin, but the capacity of these agents to alter outcomes has been brought into question by the scrutiny of modern clinical trials. In the past 4 decades, neurohormonal blockers have been introduced into clinical practice, leading to marked reductions in morbidity and mortality in chronic HF with reduced left ventricular ejection fraction (LVEF). Despite these major advances in pharmacotherapy, our understanding of the underlying disease mechanisms of HF from epidemiological, clinical, pathophysiological, molecular, and genetic standpoints remains incomplete. This knowledge gap is particularly evident with respect to acute decompensated HF and HF with normal (preserved) LVEF. For these clinical phenotypes, no drug has been shown to reduce long-term clinical event rates substantially. Ongoing developments in the pharmacotherapy of HF are likely to challenge our current best-practice algorithms. Novel agents for HF therapy include dual-acting neurohormonal modulators, contractility-enhancing agents, vasoactive and anti-inflammatory peptides, and myocardial protectants. These novel compounds have the potential to enhance our armamentarium of HF therapeutics.

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Figure 1: Mechanisms of action of novel therapeutics for heart failure.
Figure 2: Effects of conventional versus novel inotropes on cardiac contractility in vivo.

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Acknowledgements

T.G.v.L. was supported by research grant ID 2011062 from the South-Eastern Norway Regional Health Authority. H.K. was supported by National Health Medical Research Council of Australia Program Grant ID 546272.

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Correspondence to Thomas G. von Lueder.

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T.G.v.L. has received lecture honoraria from Novartis and Vifor Pharma. H.K. has research contracts with, and has served as a consultant to, Novartis.

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von Lueder, T., Krum, H. New medical therapies for heart failure. Nat Rev Cardiol 12, 730–740 (2015). https://doi.org/10.1038/nrcardio.2015.137

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