PROBLEMS OF ANTIARRHYTHMIC THERAPY IN ATR IAL-FIBRILLATION

The prevalence of atrial fibrillation increases with age, with rates o f 2 - 5% among people over the age of 60 years. Patients may be highly symptomatic or may suffer from hemodynamic compromise or thromboembol ic complications. However, antiarrhythmic drug treatment implies probl ems like the choice of the suitable drug, the individual benefit/risk profile, and alternative treatment strategies. Experimental and clinic al data support the concept that atrial fibrillation in the clinical s etting in most cases is due to multiple reentrant wavelets. A critical number of three to six simultaneously circulating reentrant wavelets seems to be necessary for the maintenance of atrial fibrillation. Cons equently, antiarrhythmic drugs may terminate or prevent atrial fibrill ation by prolonging the refractory period or slowing conduction veloci ty, thereby leading to conduction block. In clinical practice, antiarr hythmic therapy may act by slowing of the ventricular rate due to depr ession of atrioventricular nodal conduction or by termination and/or p revention of atrial fibrillation. Digitalis is commonly used for the c ontrol of the ventricular rate. Betablocking drugs and verapamil are e ffective in this respect during exercise performance. For antiarrhythm ic conversion and prophylaxis of recurrences of atrial fibrillation, c lass Ia (e.g., quinidine), Ic (e.g., flecainide and propafenone), and class III (e.g., amiodarone and sotalol) drugs of the Vaughan Williams classification are useful. Presently, no general concept exists wheth er medical or electrical cardioversion should be used as a first line approach for termination of atrial fibrillation. In the individual pat ient with atrial fibrillation, the potential benefit of restoring sinu s rhythm must be weighed against the morbidity and mortality of the ar rhythmia and the morbidity and mortality of the antiarrhythmic agents used. Besides limited efficacy, concerns regarding the safety profile of quinidine have been raised by a meta-analysis showing an increased mortality in patients randomized to quinidine compared to placebo. Fur thermore, an excess cardiac and arrhythmic death risk has been reporte d in patients with atrial fibrillation and a history of congestive hea rt failure mainly treated by class Ia and Ic agents. Because of the ve ry complex benefit/risk profile, a final assessment of the role of ant iarrhythmic medication for conversion and prevention of recurrences of atrial fibrillation is presently not possible. Randomized double-blin d studies incorporating different therapeutic strategies and endpoints are therefore necessary.