ß1-Adrenergic receptor Arg389Gly polymorphism affects the antiarrhythmic efficacy of flecainide in patients with coadministration of ß-blockers.

OBJECTIVE: ß1-Adrenergic receptor (ß1-AR) stimulation modulates the antiarrhythmic activities of sodium channel blockers. The ß1-AR Gly389 variant shows a marked decrease in agonist-stimulated cyclic AMP production compared with that of the wild-type Arg389 in vitro. We investigated whether the Arg389Gly polymorphism affects the efficacy of flecainide, a typical sodium channel blocker, in patients with or without coadministration of ß-blockers. METHODS: The effects of the ß1-AR Arg389Gly polymorphism on the antiarrhythmic efficacy of flecainide were compared between with and without coadministered ß-blockers in 159 patients with supraventricular tachyarrhythmia. The antiarrhythmic efficacy of flecainide was assessed for at least 2 months by evaluating symptomatology, 12-lead ECGs, and Holter monitoring results. RESULTS: Genetic differences in the antiarrhythmic efficacy of flecainide were observed in patients with coadministration of ß-blockers. Tachyarrhythmia was well controlled in 60% of Arg389-homozygotes, 30% of Gly389-heterozygotes, and 0% of Gly389-homozygotes (P=0.001). In contrast, no difference in the antiarrhythmic efficacy was observed among the three genotypes in the patients without coadministration of ß-blockers (64, 70, and 60%, respectively). Heart rate in tachyarrhythmia in patients treated with flecainide was significantly higher in Gly389 carriers than in Arg389-homozygotes (P=0.013). CONCLUSION: The Gly389 polymorphism decreased the antiarrhythmic efficacy of flecainide when coadministered with ß-blockers. The results indicate that the Arg389Gly polymorphism may play an important role in predicting the efficacy of flecainide in patients with coadministration of ß-blockers.