Tocainide and metoprolol: an efficacious therapeutic combination in the treatment of premature ventricular beats

A double-blind crossover study was performed in 20 patients to verify the efficacy of tocainide plus metoprolol in patients with premature ventricular contractions (PVCs) class Lown greater than or equal to 2 (mean frequency greater than or equal to 30/h) judged as being "stable" by at least three basal 24-h Holter ECGs with PVC variation of less than +/- 25%. All 20 patients were submitted to a placebo period; and all were subsequently randomized to therapy with tocainide 1800 mg/day or metoprolol 200 mg/day for 15 days and then to tocainide 1800 mg + metoprolol 200 mg/day or tocainide 1200 mg + metoprolol 200 mg/day for 15 days, followed by a crossover of the two combination treatments. At steady state in every stage we controlled for plasma levels of the drugs, a 24-h Holter recording, and a 12-lead ECG. A modified Lown score was evaluated together with the Lown class. Tocainide (mean plasma level 3.3 +/- 0.7 micrograms/ml) was efficacious in 3 of 8 patients, the modified Lown score decreased from 63 +/- 32 (placebo period) to 42 +/- 27 (p less than 0.01) and Lown 4B arrhythmias were abolished in 3 of 4 patients. Metoprolol (mean plasma level 97.4 +/- 89.6 ng/ml) was efficacious in 2 of 10 patients; the modified Lown score and Lown classes did not change significantly. Administration of tocainide 1200 mg + metoprolol 200 mg obtained a positive response in 9 of 12 patients, the modified Lown score decreased significantly compared with placebo (from 53 +/- 31 to 32 +/- 30, p less than 0.01) and Lown 4B arrhythmias were abolished in 2 of 5 cases. Tocainide 1800 mg plus metoprolol 200 mg was scarcely tolerated owing to neurologic and gastroenteric side effects, and only three patients completed this stage with no better antiarrhythmic results compared to the lower dose. In conclusion, the combination of tocainide at 1200 mg and metoprolol 200 mg is well tolerated, efficacious in a high percentage of patients, and superior to single drug therapy in patients with stable PVCs.