Lack of significant arrhythmogenicity from chronic theophylline and beta-2-adrenergic combination therapy in asthmatic subjects.

We monitored 14 asthmatic subjects (aged 18 to 60 years), with multiple 24-hour electrocardiogram (Holter) recordings, who were taking continuous sustained-release theophylline and beta-2-adrenergic therapy for control of their symptoms. All of the patients were enrolled in an efficacy study for the antiasthmatic drug lodoxamide. No patient demonstrated intrinsic cardiac disease by history or by a standard 12-lead electrocardiogram recording prior to entry into the study. All of the patients were stable at the beginning of the study while on therapeutic theophylline concentrations and inhaled and oral beta-2-adrenergics. Attempts were made to decrease the theophylline dosage by sequentially reducing the dose each week to one-half, one-quarter, and discontinuation. Holter monitoring was repeated at the end of each week of a new dose level. Five patients were able to reduce dosage and eight were able to discontinue theophylline completely. Theophylline therapy was associated with a higher mean heart rate (85.4 vs 79.9 bpm). The combination of theophylline and beta-2-adrenergics therapy was not associated with quantitative or qualitative changes in atrial or ventricular ectopic activity over beta-2-adrenergic therapy alone.