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Current Medicinal Chemistry
ISSN (Print): 0929-8673
ISSN (Online): 1875-533X
VOLUME: 11
ISSUE: 1
DOI: 10.2174/0929867043456241









Pharmacological Approaches in the Treatment of Atrial Fibrillation

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Author(s): Juan Tamargo, Ricardo Caballero and Eva Delpon
Pages 13-28 (16)
Abstract:
Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and is associated with substantial cardiovascular morbidity and mortality. The arrhythmia can be initiated and / or maintained by rapidly firing foci, single- and multiple-circuit reentry. Once initiated, AF alters atrial electrical and structural properties (atrial remodeling) in a way that promotes its own maintenance and recurrence and may alter the response to antiarrhythmic drugs. Thus, initial episodes of paroxysmal (self-terminating) AF lengthens to the point where the arrhythmia becomes persistent (requires cardioversion to restore sinus rhythm) and permanent. AF usually requires a trigger for initiation and a favorable electrophysiological and / or anatomical substrate for maintenance. The substrate includes both cardiovascular (coronary artery disease, valvular heart disease, heart failure, hypertension, dilated cardiomyopathy) and non cardiovascular diseases (thyrotoxicosis, pulmonary diseases). Accordingly, the initial step in patients with AF requires a careful assessment of symptoms and identification of underlying reversible triggers and potentially modifiable underlying structural substrate and treat them aggressively.. In contrast to other cardiac arrhythmias, antiarrhythmic drugs (ADs) are the mainstay of therapy. Long-term treatment of AF is directed to restore and maintain the sinus rhythm with class I and III ADs (rhythm-control) or to allow AF to persist and ensure that the ventricular rate is controlled (rate-control) with atrioventricular nodal blocking drugs (digoxin, β-blockers, verapamil, diltiazem) and prevent thromboembolic complications with anticoagulants. However, the long-term efficacy of ADs for preventing AF recurrence is far from ideal, because of limited efficacy (AF recurs in at least one-half of the patients) and potential side effects, particularly proarrhythmia. Thus, the choice of the appropriate AD will depend on the temporal pattern of the arrhythmia, the presence of associated diseases, easy of administration and adverse effects profile, particularly the risk of proarrhythmia. The recent finding that angiotensin converting enzyme inhibitors and β-blockers reduce the incidence of AF in patients post myocardial infarction with left ventricular dysfunction confirmed the importance of targeting the underlying arrhythmogenic substrate. This review focuses on the mechanisms underlying AF and the mechanism of action and the efficacy and safety profile of the ADs used in the treatment of atrial fibrillation. The advantages and disadvantages of rhythm and rate control, the role pill in a pocket concept and the role of the new ADs are dicussed.
Keywords:
atrial fibrillation, antiarrhythmic drugs, rhythm-control, rate-control, side effects
Affiliation:
Department of Pharmacology, School of Medicine, Universidad complutense, 28040 Madrid, Spain.