Midodrine: a role in the management of neurocardiogenic syncope
Open accessAbstract
Objective: To determine the benefit of midodrine, an α agonist, on symptom frequency and haemodynamic responses during head up tilt in patients with neurocardiogenic syncope. Setting: Cardiovascular investigation unit (a secondary and tertiary referral centre for the investigation and management of syncope). Patients: 16 outpatients (mean (SD) age 56 (18) years; five men) with frequent hypotensive symptoms (more than two syncopal episodes and fewer than 20 symptom free days per month), and reproducible syncope with glyceryl trinitrate (GTN) during head up tilt. Design and intervention: Randomised double blind placebo controlled study. Patients were randomised to receive either placebo or midodrine for one month. Symptom events were recorded during each study month. At the end of each study month patients completed a quality of life scoring scale (Short Form 36) and a global assessment of therapeutic response. They received GTN with head up tilt for measurement of heart rate (electrocardiography), phasic blood pressure (digital photoplethysmography), and thoracic fluid index (transthoracic impedance plethysmography) during symptom provocation. Results: Patients administered midodrine had an average of 7.3 more symptom free days than those who received placebo (95% confidence interval (CI) 4.6 to 9; p < 0.0001). Eleven patients reported a positive therapeutic response with midodrine (p = 0.002). All domains of quality of life showed improvement with midodrine, in particular physical function (8.1; 95% CI 3.7 to 12.2), energy and vitality (14.6; 95% CI 7.3 to 22.1), and change in health status (22.2; 95% CI 11 to 33.4 ). Fourteen patients who were given placebo had tilt induced syncope compared with six given midodrine (p = 0.01). Baseline supine systolic blood pressure was higher and heart rate lower in patients who received midodrine than in those who were given placebo ( p < 0.05). A lower thoracic fluid index in patients administered midodrine indicates increased venous return when supine and during head up tilt. There were no serious adverse effects. Conclusions: Midodrine had a conspicuous beneficial effect on symptom frequency, symptoms during head up tilt, and quality of life. Midodrine is recommended for the treatment of neurocardiogenic syncope in patients with frequent symptoms.
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None of the midodrine studies were conventional placebo-controlled randomized clinical trials of moderately to severely symptomatic patients.
“None of the studies were conventional, placebo-controlled, randomized clinical trials of moderately to severely symptomatic patients.125–128”
From 2015 Heart Rhythm Society Expert Consensus Statement on the Diagnosis and Treatment of Postural Tachycardia Syndrome, Inappropriate Sinus Tachycardia, and Vasovagal Syncope (2015) · cites this paper as [127]
The Patients and methods section describes a randomized, double-blind, placebo-controlled midodrine trial, contrary to the claim that none of the cited studies had those features. The Abstract describes participants with frequent symptoms—more than two syncopal episodes and fewer than 20 symptom-free days per month. The trial used a crossover design, so it was not a conventional parallel-group trial, but the source does not support the blanket characterization. (LLM, conf=0.84)
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Experimental — accuracy not yet measuredFour randomized trials of midodrine have shown a consistent risk reduction of approximately 70%.
“Four randomized trials on midodrine have shown a consistent risk reduction of approximately 70%.”
From 2015 Heart Rhythm Society Expert Consensus Statement on the Diagnosis and Treatment of Postural Tachycardia Syndrome, Inappropriate Sinus Tachycardia, and Vasovagal Syncope (2015) · cites this paper as [127]
The Patients and methods section describes one randomized crossover trial, not four trials. The Results report fewer tilt-induced syncopal episodes with midodrine; the reported counts of 14 on placebo versus 6 on midodrine correspond to an approximately 57% reduction, not a consistent reduction of approximately 70% across trials. Page numbers are unavailable in our copy. (LLM, conf=0.91)
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- Authors
- Ward, C. R., Gray, J. C., Gilroy, J. J., & Kenny, R. A.
- Affiliations
- Royal Victoria Infirmary (GB)
- Corresponding author
- Kenny, R A
- ORCID
- Kenny, R A
- Venue
- Heart
- Publisher
- BMJ
- Published
- 1998-01-01
- Volume
- 79
- Issue
- 1
- Pages
- 45-49
- ISSN
- 1355-6037 (ISSN-L)
- 1468-201X
- PMC
- PMC1728578
- OpenAlex
- W2120769605
- Semantic Scholar
- 8c8b308da301fd99036cd9943d91f93c05304560
- Cited by
- 249
- References
- 34
- Citations by year
- 2025: 4 · 2024: 2 · 2023: 1 · 2022: 4 · 2021: 10 · 2020: 1 · 2019: 4 · 2018: 4 · 2017: 9 · 2016: 7 · 2015: 5 · 2014: 15 · 2013: 7 · 2012: 9
- FWCI
- 16.68
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Heart (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Surgery › Cardiovascular Syncope and Autonomic Disorders
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Rate Variability and Autonomic Control
- Life Sciences › Neuroscience › Neurology › Vestibular and auditory disorders
- Keywords
- midodrine, vasovagal syncope, orthostatic intolerance, alpha-adrenergic agonists, head-up tilt, nitroglycerin, symptom frequency, quality of life, venous return, blood pressure, heart rate, adverse effects, treatment response assessment
- MeSH terms
- Adrenergic alpha-Agonists, Blood Pressure, Cardiography, Impedance, Double-Blind Method, Female, Heart Rate, Humans, Male, Middle Aged, Midodrine, Cross-Over Studies, Tilt-Table Test, Syncope, Vasovagal
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