Midodrine for the Prevention of Vasovagal Syncope

the POST 4 investigators

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32 Scopus citations


Background: Recurrent vasovagal syncope is common, responds poorly to treatment, and causes physical trauma and poor quality of life. Midodrine prevents hypotension and syncope during tilt tests in patients with vasovagal syncope. Objective: To determine whether midodrine can prevent vasovagal syncope in usual clinical conditions. Design: Randomized, double-blind, placebo-controlled clinical trial. (ClinicalTrials.gov: NCT01456481) Setting: 25 university hospitals in Canada, the United States, Mexico, and the United Kingdom. Patients: Patients with recurrent vasovagal syncope and no serious comorbid conditions. Intervention: Patients were randomly assigned 1:1 to placebo or midodrine and followed for 12 months. Measurements: The primary outcome measure was the proportion of patients with at least 1 syncope episode during follow-up. Results: The study included 133 patients who had had a median of 6 syncope episodes in the prior year (median age, 32 years; 73% female). Compared with patients receiving placebo, fewer patients receiving midodrine had at least 1 syncope episode (28 of 66 [42%] vs. 41 of 67 [61%]). The relative risk was 0.69 (95% CI, 0.49 to 0.97; P = 0.035). The absolute risk reduction was 19 percentage points (CI, 2 to 36 percentage points), and the number needed to treat to prevent 1 patient from having syncope was 5.3 (CI, 2.8 to 47.6). The time to first syncope was longer with midodrine (hazard ratio, 0.59 [CI, 0.37 to 0.96]; P = 0.035; log-rank P = 0.031). Adverse effects were similar in both groups. Limitation: Small study size, young and healthy patients, relatively short observation period, and high proportion of patients from 1 center. Conclusion: Midodrine can reduce the recurrence of syncope in healthy, younger patients with a high syncope burden.

Original languageEnglish (US)
Pages (from-to)1349-1356
Number of pages8
JournalAnnals of internal medicine
Issue number10
StatePublished - Oct 1 2021

Bibliographical note

Funding Information:
This study was funded by the Canadian Institutes of Health Research, placebo was provided gratis by Shire Pharmaceuticals and Apotex, and the companies provided active drug at cost. None of these funders had any role in the design, conduct, or analysis of the study or in the decision to submit the manuscript for publication. The authors

Publisher Copyright:
© 2021 American College of Physicians


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