Limitations of head-up tilt test for evaluating the efficacy of therapeutic interventions in patients with vasovagal syncope: Results of controlled study of etilefrine versus placebo

Objectives. This study assessed the efficacy of oral etilefrine (10 mg three times day) in preventing positive response to head-up tilt testing. Background. Previous reports have suggested that oral etilefrine can be effective either in preventing positive response to head-up tilt testing or in reducing syncopal recurrences in patients with vasovagal syncope. Up to now most studies assessing drug therapy in these patients have been uncontrolled. Methods. This was randomized double-blind crossover study of etilefrine versus placebo in 30 consecutive patients with syncope and baseline positive head-up tilt test. After the first test, patients had no treatment for 3 days and were randomized to receive etilefrine or placebo for 4 additional days. They underwent tilt testing under treatment and again after 3 days of washout; they then received the alternative treatment for 4 days, and third test was performed. Results. Head-up tilt test results were negative in 13 (43%) patients with etilefrine and 15 (50%) with placebo (p = NS). Therefore, the statistical power of the study was only 10%. The rate of positive responses decreased with repeated testing irrespective of the assigned treatment: positive response was obtained during the second head-up tilt test in 20 patients (10 with placebo, 10 with etilefrine) but in only 12 during the third (7 with etilefrine, 5 with placebo) (p < 0.05). Conclusions. Oral etilefrine (10 mg three times day) was not superior to placebo in preventing positive response to head-up tilt testing. Despite low statistical power, the high rate of negative response with placebo (50%) suggests that controlled trials are needed to assess the real efficacy of any treatment in patients with vasovagal syncope.