Document Detail

Class III antiarrhythmic agents in cardiac failure: lessons from clinical trials with a focus on the Grupo de Estudio de la Sobrevida en la Insuficiencia Cardiaca en Argentina (GESICA).
MedLine Citation:
PMID:  10568669     Owner:  NLM     Status:  MEDLINE    
The results of previous clinical trials, in a variety of clinical settings, showed that class I agents may consistently increase mortality in sharp contrast to the effects of beta blockers. Attention has therefore shifted to class III compounds for potential beneficial effects on long-term mortality among patients with underlying cardiac disease. Clinical trials with d-sotalol, the dextro isomer (devoid of beta blockade) of sotalol, showed increased mortality in patients with low ejection fraction after myocardial infarction and in those with heart failure; whereas in the case of dofetilide, the impact on mortality was neutral. Because of the complex effects of its actions as an alpha-adrenergic blocker and a class III agent, the impact on mortality of amiodarone in patients with heart failure is of particular interest. A meta-analysis of 13 clinical trials revealed significant reductions in all-cause and cardiac mortality among patients with heart failure or previous myocardial infarction. Among these were 5 controlled clinical trials that investigated the effects of amiodarone on mortality among patients with heart failure. None of these trials was large relative to the beta-blocker trials in the postinfarction patients. However, the larger 2 of the 5 amiodarone trials produced discordant effects on mortality, neutral in one and significantly positive in the other. Some of the differences may be accounted for by the differences in eligibility criteria and baseline characteristics. Future trials that may be undertaken to resolve the discrepancies may need to allow for the newer findings on the effects of concomitant beta blockers, implantable devices, and possibly, spironolactone. All these modalities of treatment have been shown in controlled clinical trials to augment survival in patients with impaired ventricular function or manifest heart failure. Additional trials, some of which are currently in progress, compare amiodarone with implantable devices and other therapeutic interventions, and should help to clarify the optimal management strategy for patients with underlying heart failure.
H C Doval
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Publication Detail:
Type:  Journal Article; Review    
Journal Detail:
Title:  The American journal of cardiology     Volume:  84     ISSN:  0002-9149     ISO Abbreviation:  Am. J. Cardiol.     Publication Date:  1999 Nov 
Date Detail:
Created Date:  1999-12-01     Completed Date:  1999-12-01     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0207277     Medline TA:  Am J Cardiol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  109R-114R     Citation Subset:  AIM; IM    
Instituto del Corazon, Hospital Italiano, Buenos Aires, Argentina.
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MeSH Terms
Amiodarone / adverse effects,  therapeutic use*
Anti-Arrhythmia Agents / adverse effects,  therapeutic use*
Clinical Trials as Topic
Heart Failure / drug therapy*,  mortality
Survival Rate
Tachycardia, Ventricular / drug therapy*,  mortality
Treatment Outcome
Reg. No./Substance:
0/Anti-Arrhythmia Agents; 1951-25-3/Amiodarone

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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