Avoiding interpretive pitfalls when assessing arrhythmia suppression after myocardial infarction: Insights from the long-term observations of the placebo-treated patients in the Cardiac Arrhythmia Pilot Study (CAPS)

The Cardiac Arrhythmia Pilot Study (CAPS) was a 1 year trial that analyzed the safety and effectiveness of arrhythmia suppression in 502 patients surviving acute myocardial infarction who had ≥10 ventricular premature depolarizations/h or ≥5 runs of ventricular tachycardia on a Holter recording obtained 6 to 60 days after the acute infarction. Because 100 of these patients received placebo in a double-blind fashion for 1 year, a comprehensive objective analysis was performed of spontaneous arrhythmia changes based on real data rather than statistical estimates. In the CAPS placebo group, 19% developed some serious clinical event in 1 year (death, heart failure, proarrhythmia) that could likely be attributable to antiarrhythmic drug toxicity. A significant reduction in the frequency of ventricular premature depolarizations (p = 0.004) occurred in the first few weeks of "therapy," with a further significant (p < 0.04) decrease between 3 to 12 months. After initiation of placebo antiarrhythmic therapy, 27% had "apparent ventricular premature depolarization suppression" (70% reduction) after one Holter recording evaluation and nearly half (48%) after six Holter recordings to assess suppression were performed. It is concluded that 1) setting a higher percent suppression goal or obtaining multiple baseline Holter recordings decreases the chance of mistaking suppression for spontaneous variability: 2) obtaining frequent individual Holter recordings over the course of drug therapy actually increases the chance of sampling during one extreme variability period, the result of which is to incorrectly infer "suppression" or "proarrhythmia": and 3) runs of ventricular tachycardia occur in the CAPS study group infrequently, are of low density and exhibit extreme variability such that a primary suppression goal focused on runs of ventricular tachycardia is not a reliable end point for assessing antiarrhythmic therapy.