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Vasovagal syncope, postural orthostatic tachycardia syndrome, and inappropriate sinus tachycardia comprise a heterogenous group of common autonomic disorders that are associated with significant symptoms that impair quality of life. Clinical management of these disorders should prioritize conservative non-pharmacological therapies and consider incorporating pharmacological agents for recurrences. The selection and titration of medications may be complicated by the occurrence of potentially overlapping pathophysiological variants, differences in specific clinical presentations, and commonly associated comorbidities. However, with appropriate long-term management and specialist input, most patients note both symptomatic improvement and functional restoration over time. [ABSTRACT FROM AUTHOR]

Aims: Vasovagal syncope (VVS) is a common clinical condition that lacks effective medical therapies despite being associated with significant morbidity. Current guidelines suggest that midodrine, a prodrug for an α1-adrenergic receptor agonist, might suppress VVS but supporting studies have utilized heterogeneous methods and yielded inconsistent results. To evaluate the efficacy of midodrine to prevent syncope in patients with recurrent VVS by conducting a systematic review and meta-analysis of published studies., Methods and Results: Relevant randomized controlled trials were identified from the MEDLINE, Embase, CENTRAL, and CINAHL databases without language restriction from inception to June 2021. All studies were conducted in clinical syncope populations and compared the benefit of midodrine vs. placebo or non-pharmacological standard care. Weighted relative risks (RRs) were estimated using random effects meta-analysis techniques. Seven studies (n = 315) met inclusion criteria. Patients were 33 ± 17 years of age and 31% male. Midodrine was found to substantially reduce the likelihood of positive head-up-tilt (HUT) test outcomes [RR = 0.37 (0.23-0.59), P < 0.001]. In contrast, the pooled results of single- and double-blind clinical trials (I2 = 54%) suggested a more modest benefit from midodrine for the prevention of clinical syncope [RR = 0.51 (0.33-0.79), P = 0.003]. The two rigorous double-blind, randomized, placebo-controlled clinical trials included 179 VVS patients with minimal between-study heterogeneity (I2 = 0%) and reported a risk reduction with midodrine [RR = 0.71 (0.53-0.95), P = 0.02]., Conclusions: Midodrine is effective in preventing syncope induced by HUT testing and less, but still significant, RR reduction in randomized, double-blinded clinical trials., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2022. For permissions, please email: journals.permissions@oup.com.)