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Efficacy of Midodrine vs Placebo in Neurogenic Orthostatic Hypotension: A Randomized, Double-blind Multicenter Study
Abstract
Objective. —To evaluate the efficacy of a 10-mg dose of midodrine 3 times per day in improving blood pressure (BP) and ameliorating symptoms of orthostatic hypotension in patients with neurogenic orthostatic hypotension. Midodrine hydrochloride, an α=agonist, could improve orthostatic BP by increasing vasomotor and venomotor tone. Design/Methods. —A total of 171 patients with orthostatic hypotension participated in a multicenter, randomized, placebo-controlled study. They were randomized to a 10-mg dose of midodrine or placebo 3 times per day in a 6-week study, comprising single-blind run-in (at week 1) and washout at weeks 5 and 6, with an intervening double-blind period (weeks 2 to 4). Setting. —Twenty-five centers, with most patients evaluated in referral centers. Main Outcome Measures. —The primary end points were improvement in standing systolic BP, symptoms of lightheadedness, and a global symptom relief score (by the investigator and patient separately). Results. —Nine patients were not evaluable because of noncompliance or taking concomitant vasoactive medications (3 in the midodrine group, 6 in the placebo group). In the evaluable patients, midodrine resulted in improvements in standing systolic BP at all time points (P<.001 at visits 2,3,4, and 5), in reported symptoms by the end of the second week of treatment (P=.001), and in the global symptom relief score rated by both the patient (P=.03) and the investigator (P<.001). There was no effect by center, severity of orthostatic hypotension, use of fludrocortisone or compression garments, or diagnosis. The main adverse effects were those of pilomotor reactions, urinary retention, and supine hypertension. Conclusions. —Midodrine is efficacious and safe in the treatment of neurogenic orthostatic hypotension.
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“Midodrine (2.5-10 mg t.i.d) was shown to be effective in three randomized placebo-controlled trials. 324-326”
From 2018 ESC Guidelines for the diagnosis and management of syncope (2018) · cites this paper as [325]
In the citing paper
“There is no doubt that midodrine increases BP both in the supine and upright posture, and ameliorates the symptoms of OH.”
From 2018 ESC Guidelines for the diagnosis and management of syncope (2018) · cites this paper as [325]
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Developed in collaboration with, European Heart Rhythm Association (EHRA), Heart Failure Association (HFA), and Heart Rhythm Society (HRS), societies, E. B. T. F., European Society of Emergency Medicine (EuSEM), European Federation of Internal Medicine (EFIM), European Union Geriatric Medicine Society (EUGMS), American Geriatrics Society (AGS), European Neurological Society (ENS), et al. (2009) · European Heart Journal · doi:10.1093/eurheartj/ehp298 · Cited by 2,040
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Brignole, M., Moya, A., de Lange, F. J., Deharo, J.-C., Elliott, P. M., Fanciulli, A., Fedorowski, A., Furlan, R., Kenny, R. A., Martín, A., et al. (2018) · European Heart Journal · doi:10.1093/eurheartj/ehy037 · Cited by 1,951
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Shen, W.-K., Sheldon, R. S., Benditt, D. G., Cohen, M. I., Forman, D. E., Goldberger, Z. D., Grubb, B. P., Hamdan, M. H., Krahn, A. D., Link, M. S., et al. (2017) · Heart Rhythm · doi:10.1016/j.hrthm.2017.03.004 · Cited by 478
“There is a dose-dependent effect, in standing blood pressure (459,460,462,463,466,467).”
BackgroundWenning, G. K., Colosimo, C., Geser, F., & Poewe, W. H. (2004) · The Lancet Neurology · doi:10.1016/s1474-4422(03)00662-8 · Cited by 470
Metadata
- Authors
- Low, P. A.
- Corresponding author
- Low, Phillip A.
- ORCID
- Low, Phillip A.
- Venue
- JAMA
- Publisher
- American Medical Association (AMA)
- Published
- 1997-04-02
- Volume
- 277
- Issue
- 13
- Pages
- 1046
- ISSN
- 0002-9955 (ISSN-L)
- 0098-7484
- OpenAlex
- W4294549596
- Cited by
- 425
- References
- 0
- Citations by year
- 2026: 9 · 2025: 17 · 2024: 11 · 2023: 10 · 2022: 13 · 2021: 16 · 2020: 23 · 2019: 18 · 2018: 15 · 2017: 22 · 2016: 20 · 2015: 25 · 2014: 27 · 2013: 18 · 2012: 20
- FWCI
- 8.21
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- JAMA (publishedVersion)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Syncope and Autonomic Disorders
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Rate Variability and Autonomic Control
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Blood Pressure and Hypertension Studies
- Keywords
- midodrine, neurogenic orthostatic hypotension, alpha-adrenergic agonists, blood pressure, lightheadedness, symptom relief, vascular tone, adverse effects, urinary retention, supine hypertension
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