A PLACEBO-CONTROLLED TRIAL OF INTRAVENOUS AND ORAL DISOPYRAMIDE FOR PREVENTION OF NEURALLY-MEDIATED SYNCOPE INDUCED BY HEAD-UP TILT

Objectives. A double-blind randomized trial was designed to determine the efficacy of intravenous and oral disopyramide phosphate in prevent ing neurally mediated syncope induced by a head-up tilt test. Backgrou nd. Neurally mediated syncope is a frequent cause of syncope and may b e induced by head-up tilt testing. Recent uncontrolled trials have sug gested that disopyramide may be an effective therapy in patients with neurally mediated syncope. Methods. Twenty-two consecutive patients wi th recurrent neurally mediated syncope and two or more successive posi tive head-up tilt test responses were randomly allocated to receive ei ther intravenous disopyramide or placebo. Head-up tilt testing at 60 d egrees was performed for 15 min. If presyncope or syncope was not prov oked, isoproterenol infusion was started at a rate of 1 mu g/min and t he rate gradually increased until a 25% increase in heart rate was ach ieved. Eleven patients were subsequently randomized in crossover fashi on to receive oral disopyramide (800 mg/day) or placebo during 1 week. The primary end point was prevention of syncope or presyncope provoke d by head-up tilt testing. Results. Head-up tilt test results were pos itive for syncope in 12 (75%) of 16 patients receiving intravenous pla cebo and in 12 (60%) of 20 patients receiving disopyramide (p = 0.55 F isher exact test, 95% confidence interval [CI]-14% to 40%). In the int ravenous phase, complete crossover was achieved in 15 patients. Head-u p tilt test results during this phase were positive in 13 patients (87 %) receiving placebo and in 12 patients (80%) receiving disopyramide ( p = 0.50 Fisher exact test, 95% CI-19% to 32%) and were positive in al l patients receiving their initially randomized drug or placebo. In th e oral phase, head-up tilt results were positive in only two patients (18%) assigned to placebo and in three patients (27%) receiving disopy ramide (p = 0.54 Fisher exact test, 95% CI-42% to 24%). A mean follow up time of 29 +/- 8 months was obtained in 21 of the 22 patients. Sync ope recurred in 3 (27%) of the 11 patients receiving disopyramide and 3 (30%) of the 10 patients not treated pharmacologically (p > 0.05). C onclusions. Intravenous disopyramide was ineffective for the preventio n of neurally mediated syncope provoked by head-up tilt testing. No si gnificant effect was observed after oral therapy with disopyramide. Th ere was a striking decrease in the incidence of positive tilt test res ults over time regardless of intervention, thus discouraging the use o f head-up tilt as the single method of assessing therapeutic efficacy. Recurrence of syncope after the investigative protocol was infrequent over long term follow-up regardless of treatment group.