Pharmacologic prevention of recurrent vasovagal syncope: A systematic review and network meta-analysis of randomized controlled trials

Vasovagal syncope (VVS) is a transient loss of consciousness that currently imposes a high burden on health care systems with limited evidence of the comparative efficacy of available pharmacologic in-terventions. This study aims to compare all pharmacologic therapies suggested in randomized controlled trials (RCTs) through system-atic review and network meta-analysis. A systematic search in PubMed, Embase, Web of Science, and Cochrane Library was con-ducted to identify RCTs evaluating pharmacologic therapies for pa-tients with VVS. The primary outcome was spontaneous VVS recurrence. The secondary outcome was a positive head-up tilt test (HUTT) after receiving intervention, regarded as a lower level of evidence. Pooled risk ratio (RR) with 95% confidence interval (CI) was calculated using random-effect network meta-analysis. Pairwise meta-analysis for comparison with placebo was also per-formed when applicable. The surface under the cumulative ranking curve analysis was conducted to rank the treatments for each outcome. Twenty-eight studies with 1744 patients allocated to different medications or placebo were included. Network meta-analysis of the reduction in the primary outcome showed efficacy for midodrine (RR 0.55; 95% CI 0.35-0.85) and fluoxetine (espe-cially in patients with concomitant anxiety) (RR 0.36; 95% CI 0.16-0.84). In addition, midodrine and atomoxetine were superior to other treatment options, considering positive HUTT (RR 0.37; 95% CI 0.23-0.59; and RR 0.49; 95% CI 0.28-0.86, respectively). Overall, midodrine was the only agent shown to reduce spontaneous syncopal events. Fluoxetine also seems to be beneficial but should be studied further in RCTs. Our network meta-analysis did not find evidence of the efficacy of any other medication.