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  • Review Article
  • Published:

Drug therapy for atrial fibrillation: where do we go from here?

Nature Reviews Drug Discovery volume 4, pages 899–910 (2005)Cite this article

Key Points

  • Atrial fibrillation (AF) is the most common arrhythmia that requires medical attention.

  • Patients with significant symptoms related to AF may benefit from efforts to restore and maintain normal sinus rhythm using pharmacological agents. Currently available antiarrhythmic agents suffer from limited efficacy and frequent side effects, including the risk of provoking more serious arrhythmias.

  • Two general mechanisms interact to generate and maintain AF: triggering initiators, and changes in properties of atrial tissue that render it fibrillation-prone.

  • One strategy being used in developing new antiarrhythmic agents for AF is block of cardiac ion currents, notably an atrial-specific potassium current termed IKur.

  • An emerging concept is that AF represents a final common pathway for genetic predisposition and environmental stressors such as inflammation, oxidant stress, and activation of the renin–angiotensin and other intracellular signaling systems. Unravelling the molecular pathophysiology of the arrhythmia is defining new targets for pharmacological intervention.

Abstract

Atrial fibrillation, the most common cardiac arrhythmia requiring medical attention, has effects that range from mild symptoms to devastating stroke. Although treatments have evolved since the foxglove plant (later identified as containing digitalis) was first administered to slow the heart rate, satisfactory drug therapy has not been developed. In this review we describe present-day medical options and developments of future therapies to treat atrial fibrillation and maintain normal sinus rhythm.

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Figure 1: Sequences of cardiac activation.
Figure 2: Mechanisms in atrial fibrillation and targets for atrial stabilization.
Figure 3: 'AF begets AF'.
Figure 4: Three electrocardiographic rhythm strips recorded in the same patient over a 6-hour period after initiation of an anti-arrhythmic drug to treat atrial fibrillation.

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Author information

Authors and Affiliations

  1. Division of Cardiology, University of Washington School of Medicine, 1959 NE Pacific Street, Room AA502, Health Sciences Bldg, Box 356422, Seattle, 98195-6422, Washington, USA

    Richard L. Page

  2. Departments of Medicine and Pharmacology and the Oates Institute for Experimental Therapeutics, Vanderbilt University School of Medicine, 2222 Pierce Avenue, Nashville, 37232, Tennesse, USA

    Dan M. Roden

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  1. Richard L. Page
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Correspondence to Richard L. Page.

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Competing interests

R.L.P. has previously served as consultant to AstraZeneca, Glaxo-SmithKline, Reliant Pharmaceuticals, Cardiome and Procter & Gamble Pharmaceuticals. He is now a consultant to Berlex Laboratories, Sanofi Synthelolab and Alza. D.M.R. has served as consultant to AstraZeneca, Sanofi and Cardiome.

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DATABASES

Entrez Gene

ACE

Connexin-40

Connexin-43

Conexxin-45

C-reactive protein

Factor II

Factor VII

Factor IX

Factor X

HERG

HMG-CoA reducatse

interleukin-6

KCNA5

KCNE2

KCNJ2

KCNQ1

matrix metalloproteinase-9

TGFβ

FURTHER INFORMATION

The Pharmacogenetics and Pharmacogenomics Knowledge Base

Glossary

ARRHYTHMIA

An abnormal rhythm of the heart. Also referred to as dysrhythmias, arrhythmias can occur in the atria and ventricles. Atrial fibrillation is an arrhythmia of the atria, although it conducts to the ventricles such that the pulse is irregularly irregular.

CARDIAC OUTPUT

The forward delivery of blood from the heart, usually reported in litres per minute.

PULMONARY OEDEMA

A condition in which the lungs become congested and fluid may leak into gas-exchange chambers called alveoli, usually due to left ventricular failure.

CARDIAC REMODELLING

The concept that the properties of the heart change with environmental stressors. In AF, such remodelling may serve to perpetuate the arrhythmia.

ATRIAL FLUTTER

An atrial arrhythmia that can also result in an irregular ventricular response. Unlike atrial fibrillation, this is a regular atrial rhythm that results from electrical reentry encircling the tricuspid valve ring.

CARDIAC ABLATION

Destruction of cardiac tissue, usually percutaneously via a specialized catheter, by applying radiofrequency electrical current.

QT PROLONGATION

The QT interval represents the time for electrical activation and inactivation of the ventricles, the lower chambers of the heart. Prolongation of the QT interval can result in the potentially lethal arrythmia known as Torsades de Pointes.

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Page, R., Roden, D. Drug therapy for atrial fibrillation: where do we go from here?. Nat Rev Drug Discov 4, 899–910 (2005). https://doi.org/10.1038/nrd1876

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