Reproducibility of Successful Drug Trials in Patients With Inducible Sustained Ventricular Tachycardia

Patients whose inducible sustained ventricular tachycardia is suppressed during serial electrophysiological testing have a small but gradually increasing actuarial incidence of recurrent arrhythmias despite therapy with the "successful" drug. In an effort to improve the predictive value of a drug response, in 1990 we began to require that our full stimulation protocol be repeated successfully several times before considering a drug to be effective. In 23 consecutive patients who had inducible sustained ventricular tachycardia which was suppressed by at least one drug during invasive serial drug testing using a standard stimulation protocol, the identical stimulation protocol was performed six times during therapy with the initially successful drug (three trials on Day 1 and three trials on Day 2). Repeat trials were completed (i.e., either all six trials were successfully finished or sustained tachycardia was induced) for 29 initially successful drugs in these 23 patients. With 18 of these 29 initially successful drugs (62%), sustained ventricular tachycardia was eventually induced during repeat trials. The eventual drug failures could not be correlated with specific drugs tested, subtherapeutic or falling serum drug levels, marked fluctuations in autonomic tone, or changes in anatomic substrate. The proportion of patients failing each repeat trial was relatively constant: 4/29 (14%) failed Trial 2, 2/25 (8%) failed Trial 3, 7/23 (30%) failed Trial 4, 2/16 (13%) failed Trial 5, and 3/14 (21%) failed Trial 6. The increase in the cumulative incidence of drug failure during repeat trials was nearly linear. Inducibility of ventricular tachycardia appears to be a probability function; a successful drug study should not be regarded as an absolute phenomenon.