What have clinical trials taught us about proarrhythmia?
Proarrhythmia is defined as the developmental of a new arrhythmia, or the worsening of a preexisting arrhythmia, following the institution of anti-arrhythmic therapy. The most important manifestation of proarrhythmia is sudden arrhythmic death. Possible mechanisms of proarrhythmia include early afterdepolarizations, dispersion of repolarization, a conduction-slowing effect that promotes reentry, and the interaction of arrhythmic drugs with ischemia. Recent trials of arrhythmic drugs have focused attention on the increase in mortality due to some of these drugs. In many studies, the effect of placebo has been compared with that of antiarrhythmic drugs on mortality in high-risk patients following myocardial infarction (MI). In most of these trials, anti-arrhythmic drugs were associated with an increase in mortality has been most clearly shown with encainide, flecainide, moricizine and d-sotalol. In addition, increased mortality has been suggested in patients treated with antiarrhythmics for atrial fibrillation especially in the presence of structural heart disease. In contrast, several post-MI benefit. This suggests that amiodarone may be safe for the treatment of arrhythmias in the post-MI patient. Further evidence will come from two majors studies (CAMIAT and EMIAT) which should be available by early 1996.
Skanes
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Division of Cardiology, University of Ottawa Heart Institute, Ottawa Civic Hospital, Ontario. mgreen@heartinst.on.ca
Green
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D000638:Amiodarone / Q000627:therapeutic use; D000889:Anti-Arrhythmia Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001145:Arrhythmias, Cardiac / Q000139:chemically induced* / Q000188:drug therapy / Q000503:physiopathology; D002986:Clinical Trials as Topic; D004562:Electrocardiography; D006801:Humans; D009203:Myocardial Infarction / Q000150:complications; D016171:Torsades de Pointes / Q000139:chemically induced / Q000503:physiopathology
D000889:Anti-Arrhythmia Agents; D000638:Amiodarone