[New anti-arrhythmics--hope or disappointment?].
The new anti-arrhythmic agents studied in the last decade have mostly come from research orientated towards determining the compounds which block the electrical currents implicated in the process of repolarisation (class III action). To this must be added dronedarone, which is related to amiodarone and as such displays the 4 classes of anti-arrhythmic properties. Pure class III agents prolong the cardiac action potential and therefore the refractory period and QT interval. The conduction velocity is unaltered. These agents act best on re-entry arrhythmias. Dofetilide is a prototype. The class III action is linked to blockade of the Ikr current and can paradoxically lower it at increased heart rates. Dofelitide has not shown a harmful effect on the survival of high risk ischaemic patients. The conversion of atrial tachyarrhythmias into sinus rhythm can be obtained in one to two thirds of cases. As for the prevention of these arrhythmias, its success rate can exceed 60%. On the other hand, the occurrence of torsades de pointe is in the order of 3%, justifying the initiation of treatment under hospital conditions. Ibutilide acts by blocking the Ikr and INa-s currents. Used only intravenously, this agent is capable of converting back to sinus rhythm a third of atrial fibrillation episodes and two thirds of flutter. The risk of torsades de pointe is 3.5% so this treatment must also be commenced in the hospital setting. Azimilide blocks multiple Iks channels as well as Ikr, Ica and Ina. The electrophysiological effect is sustained at rapid heart rates. When evaluated in patients with paroxysmal atrial fibrillation, azimide prolonged the interval until recurrence, associated with an excellent tolerance (torsades de pointe in 0.55% of cases). In a survival study, azimide demonstrated a neutral effect in high risk subjects with diminished ejection fraction and sinusal variability. Unlike the previous agents, dronedarone is a benzofurane with a similar structure to amiodarone but without iodine. The 800 mg dose is associated with the best risk-benefit ratio. In patients with left ventricular dysfunction, the administration of this agent has been associated with excess mortality. Two recent studies on the prevention of atrial fibrillation have demonstrated that dronedarone is moderately effective with an excellent general tolerance.
Touboul
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P
Hôpitaux de Lyon, hôpital cardiovasculaire et pneumologique Louis Pradel, Bron. paul.touboul@chu-lyon.fr
D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001145:Arrhythmias, Cardiac / Q000188:drug therapy*; D004562:Electrocardiography; D006801:Humans; D011379:Prognosis; D012307:Risk Factors; D016019:Survival Analysis
D000889:Anti-Arrhythmia Agents