Tocainide and mortality after myocardial infarction: A prospective study in conscious dogs

The production of an anterior myocardial infarction as part of an experimental animal model for sudden death was burdened by a persistently elevated mortality rate (30%) despite the use of traditional antiarrhythmic drugs. Mortality was reduced when tocainide (600 mg three times daily) was empirically administered for 4 days before and 4 days after myocardial infarction. Retrospective analysis showed that mortality at 4 days after infarction was significantly lower in the tocainide-treated dogs than in the preceding large group of dogs that had not been so treated (5 [9%] of 55, versus 64 [32%] of 199, p <0.01). This difference was still evident 30 days after myocardial infarction (13 [24%] of 55 versus 83 [42%] of 199; p <0.05). This observation led to the present prospective study in 106 dogs with a similar protocol but with a randomized sequence. At 4 days after myocardial infarction, the mortality rate was 55% lower in the tocainide group than in the control group (7 [12.5%] of 56 versus 14 [28%] of 50; p <0.05). During the 10 days after treatment withdrawal 9 (18%) of 49 dogs in the tocainide group died compared with only 2 (5%) of 36 in the control group. This rebound in mortality produced similar survival figures in the two groups at 14 and at 30 days after infarction when mortality was 30% (17 of 56) in the tocainide group and 34% (17 of 50) in the control group. The tocainide plasma levels were 7.4 ± 4 μg/ml the day before infarction and 7.2 ± 3 μg/ml 3 days after infarction. This study indicates that mortality in the first few days after myocardial infarction can be reduced by tocainide. The results may be of potential interest for the out of hospital management of patients with a recent myocardial infarction.