Midodrine Most Effective Pharmacological Intervention for Vasovagal Syncope

A systematic review and network meta-analysis published in Heart Rhythm found that midodrine had evidence to support its use for managing vasovagal syncope (VVS).

Investigators from the Tehran University of Medical Sciences in Iran searched publication databases through June 2022 for studies of pharmacological interventions for VVS.

This analysis included data from 28 studies which were conducted between 1992 and 2021, primarily in the United States (n=5), Canada (n=5), and Italy (n=4).

The pooled study population comprised 1744 patients with a mean age of 31.3±13.4 years and 38.4% were men. A subset of 1321 of the study participants were randomly assigned to receive 1 of 10 treatments or placebo to prevent syncope recurrence and 841 participants were randomly assigned to receive 1 of 13 treatments or placebo for the outcome of head-up tilt-test (HUTT)-induced syncope.

The active treatments included atenolol, atomoxetine, clonidine, disopyramide, etilefrine, fludrocortisone, fluoxetine, metoprolol, midodrine, nadolol, paroxetine, propranolol, scopolamine, and verapamil.

The incidence of syncope recurrence was reduced with fluoxetine (risk ratio [RR], 0.36; 95% CI, 0.16-0.84) and midodrine (RR, 0.55; 95% CI, 0.35-0.85) compared with placebo. Conversely, syncope recurrence was observed among more paroxetine recipients compared with placebo (RR, 3.00; 95% CI, 1.22-7.37). All other interventions (atenolol, atomoxetine, disopyramide, etilefrine, fludrocortisone, metoprolol, propranolol) did not differ significantly from placebo.

For HUTT-induced syncope, midodrine (RR, 0.37; 95% CI, 0.23-0.59) and atomoxetine (RR, 0.49; 95% CI, 0.28-0.86) reduced VVS during HUTT compared with placebo, whereas atenolol (RR, 13.00; 95% CI, 1.86-90.64) and clonidine (RR, 13.20; 95% CI, 1.77-98.35) increased VVS compared with placebo. All other interventions (atomoxetine, disopyramide, etilefrine, fluoxetine, metoprolol, nadolol, paroxetine, propranolol, scopolamine, verapamil) did not differ significantly from placebo.

In the surface under the cumulative ranking curve analysis, fluoxetine was the most favored approach for preventing spontaneous syncope (94.5%), followed by midodrine (84%). For HUTT-induced syncope, midodrine was favored most (92.2%).

This analysis is limited by the small sample sizes and the lack of direct head-to-head comparisons of pharmacological interventions.

“This network meta-analysis comparing pharmacologic interventions for VVS demonstrated midodrine’s high efficacy in preventing syncope,” the study authors wrote. “Since guidelines have not strongly backed pharmacologic approaches for VVS, this network comparison could guide clinicians in selecting appropriate treatments and help researchers design future trials.”