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  • Review Article
  • Published:

New developments in atrial antiarrhythmic drug therapy

Abstract

Atrial fibrillation (AF) is a growing clinical problem associated with increased morbidity and mortality. Currently available antiarrhythmic drugs (AADs), although highly effective in acute cardioversion of paroxysmal AF, are generally only moderately successful in long-term maintenance of sinus rhythm. The use of AADs is often associated with an increased risk of ventricular proarrhythmia, extracardiac toxicity, and exacerbation of concomitant diseases such as heart failure. AF is commonly associated with intracardiac and extracardiac disease, which can modulate the efficacy and safety of AAD therapy. In light of the multifactorial intracardiac and extracardiac causes of AF generation, current development of anti-AF agents is focused on modulation of ion channel activity as well as on upstream therapies that reduce structural substrates. The available data indicate that multiple ion channel blockers exhibiting potent inhibition of peak INa with relatively rapid unbinding kinetics, as well as inhibition of late INa and IKr, may be preferable for the management of AF when considering both safety and efficacy.

Key Points

  • Atrial fibrillation (AF) is a growing clinical problem associated with increased morbidity and mortality

  • Currently available antiarrhythmic drugs (AADs) can be highly effective in acute cardioversion of AF, but are only moderately successful in long-term maintenance of sinus rhythm and may induce adverse effects

  • AF is commonly associated with atrial electrical and structural abnormalities as well as extracardiac disease, which may induce or promote AF and determine the efficacy and safety of AAD therapy

  • Current development of anti-AF agents is focused on alteration of ion channel activity as well as upstream therapies that reduce structural substrates

  • Multiple ion channel blockers exhibiting inhibition of fast INa and late INa, IKr, and IKur are likely to be atrial-selective and may be best suited for the management of AF

  • Preventing or reversing atrial structural remodeling ('upstream therapy') seems to be beneficial for some AF pathologies, such as postoperative AF or AF associated with severe heart failure

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Figure 1: Current prominent investigational strategies for rhythm control of atrial fibrillation.
Figure 2: Opposite effect of IKur inhibition on the action potential in healthy and remodeled atria.
Figure 3: Ranolazine induces atrial-selective prolongation of the ERP and development of PRR.
Figure 4: Ranolazine produces a much greater rate-dependent inhibition of the maximal action potential upstroke velocity (Vmax) in atria than in ventricles.

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Bianca J. J. M. Brundel, Xun Ai, … Natasja M. S. de Groot

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Acknowledgements

Supported by grant HL47678 from NHLBI (C. Antzelevitch) and NYS and Florida Grand Lodges F. & A. M.

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A. Burashnikov declares no competing interests.

C. Antzelevitch declares that he is a consultant and patent holder/applicant for AstraZeneca and Gilead Sciences, Inc. He has also received grant/research support from AstraZeneca, Cardiome, Gilead Sciences, Inc., Lundbeck, and Solvay.

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Burashnikov, A., Antzelevitch, C. New developments in atrial antiarrhythmic drug therapy. Nat Rev Cardiol 7, 139–148 (2010). https://doi.org/10.1038/nrcardio.2009.245

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