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The antiarrhythmic efficacy and tolerability of encainide and quinidine were compared in an open-design study in which 50 patients with recurrent supraventricular tachyarrhythmias received intravenous encainide in an initial phase and oral encainide and quinidine in a subsequent, randomized crossover phase. Oral encainide (75 to 200 mg/day), administered to 47 patients for an average of 4.7 months, was effective in 77%, and oral quinidine (1,200 mg/day), administered to 44 patients for an average of 3.2 months, was effective in 66% of the patients (difference not significant). When the duration of therapy at each crossover period was compared, the percentage of patients who continued to take encainide was consistently higher than the percentage who continued to take quinidine (p less than 0.01). Twenty-nine percent of the patients discontinued encainide treatment, 23% because of clinical inefficacy and 6% because of adverse effects. Fifty-nine percent of the patients discontinued quinidine treatment, 20% because of inefficacy and 39% because of adverse effects. Based on antiarrhythmic efficacy, encainide is at least as effective as quinidine in the treatment of patients with supraventricular tachyarrhythmias. However, because of encainide's much greater tolerability, it was distinctly superior in terms of clinical use. This study was an open-design, randomized crossover trial to compare the efficacy and tolerability of encainide with those of quinidine in the treatment of supraventricular tachyarrhythmias.