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Randomized Trial of Ivabradine in Patients With Hyperadrenergic Postural Orthostatic Tachycardia Syndrome
Open accessAbstract
BACKGROUND Postural orthostatic tachycardia syndrome (POTS) is a complex, multifaceted disorder that impairs functional status and quality of life. Current pharmacological treatments are limited. OBJECTIVES This study investigated the effect of ivabradine (selective blocker of the Ifunny channel in the sinoatrial node) on heart rate, quality of life (QOL), and plasma norepinephrine (NE) levels in patients with hyperadrenergic POTS defined by plasma NE >600 pg/ml and abnormal tilt table test. METHODS In total, 22 patients with hyperadrenergic POTS as the predominant subtype completed a randomized, double-blinded, placebo-controlled, crossover trial with ivabradine. Patients were randomized to start either ivabradine or placebo for 1 month, and then were crossed over to the other treatment for 1 month. Heart rate, QOL, and plasma NE levels were measured at baseline and at the end of each treatment month. RESULTS The average age was 33.9 ± 11.7 years, 95.5% were women (n = 21), and 86.4% were White (n = 23). There was a significant reduction in heart rate between placebo and ivabradine (p < 0.001). Patients reported significant improvements in QOL with RAND 36-Item Health Survey 1.0 for physical functioning (p = 0.008) and social functioning (p = 0.021). There was a strong trend in reduction of NE levels upon standing with ivabradine (p = 0.056). Patients did not experience any significant side-effects, such as bradycardia or hypotension, with ivabradine. CONCLUSION Ivabradine is safe and effective in significantly improving heart rate and QOL in patients with hyperadrenergic POTS as the predominant subtype.
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In the citing paper
“One randomized placebo-controlled trial examining ivabradine demonstrated a significant reduction in HR compared to placebo, similar to the results discussed here.4”
From A Randomized Crossover Trial of Ivabradine, Propranolol, and Placebo in Postural Orthostatic Tachycardia Syndrome (2026) · cites this paper as [4]
In the citing paper
“Both ivabradine and propranolol significantly reduced the orthostatic HR increase compared to placebo, consistent with earlier studies.4,6,28”
From A Randomized Crossover Trial of Ivabradine, Propranolol, and Placebo in Postural Orthostatic Tachycardia Syndrome (2026) · cites this paper as [4]
In the citing paper
“A limited number of prior studies have examined the effects of propranolol or ivabradine on POTS.4,6,9, 10, 11, 12”
From A Randomized Crossover Trial of Ivabradine, Propranolol, and Placebo in Postural Orthostatic Tachycardia Syndrome (2026) · cites this paper as [4]
In the citing paper
“Ivabradine selectively blocks the If channels located in the sinoatrial node of the heart, lowering HR directly without impacting other systemic functions like blood pressure.4,5”
From A Randomized Crossover Trial of Ivabradine, Propranolol, and Placebo in Postural Orthostatic Tachycardia Syndrome (2026) · cites this paper as [4]
In the citing paper
“All patients were of the “hyperadrenergic subtype” and had elevated baseline norepinephrine levels.”
From A Randomized Crossover Trial of Ivabradine, Propranolol, and Placebo in Postural Orthostatic Tachycardia Syndrome (2026) · cites this paper as [4]
In the citing paper
“Ivabradine was able to lower norepinephrine levels compared to placebo.”
From A Randomized Crossover Trial of Ivabradine, Propranolol, and Placebo in Postural Orthostatic Tachycardia Syndrome (2026) · cites this paper as [4]
In the citing paper
“A 2021 single-centre RCT found that ivabradine lowered the heart rate and improved symptoms in some patients with POTS.47”
From Diagnosis and management of postural orthostatic tachycardia syndrome (2022) · cites this paper as [47]
In the citing paper
“were not eligible for inclusion due to symptom burden not being measured”
From Self-reported symptom burden in postural orthostatic tachycardia syndrome (POTS): A narrative review of observational and interventional studies (2023) · cites this paper as Taub et al., 2021
In the citing paper
“A study of ivabradine in patients with hyperadrenergic POTS reported a reduction in heart rate, improvement in quality-of-life, and a strong trend in reduction of norepinephrine levels upon standing.95”
From Sinus Tachycardia: a Multidisciplinary Expert Focused Review (2022) · cites this paper as [95]
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Self-citation
Metadata
- Authors
- Taub, P. R., Zadourian, A., Lo, H. C., Ormiston, C. K., Golshan, S., & Hsu, J. C.
- Affiliations
- University of California San Diego (US)
- Corresponding author
- Taub, Pam R.
- Venue
- Journal of the American College of Cardiology
- Publisher
- Elsevier BV
- Published
- 2021-02
- Volume
- 77
- Issue
- 7
- Pages
- 861-871
- ISSN
- 0735-1097 (ISSN-L)
- OpenAlex
- W3133439693
- Semantic Scholar
- 92f8805e778a18d378cb6b9efeb90dacd10c2a0a
- Cited by
- 122
- References
- 45
- Citations by year
- 2026: 18 · 2025: 26 · 2024: 19 · 2023: 19 · 2022: 25 · 2021: 15
- FWCI
- 18.30
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of the American College of Cardiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Amgen
- 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 › Heart rate and cardiovascular health
- Keywords
- ivabradine, postural orthostatic tachycardia syndrome, sinoatrial node, heart rate reduction, quality of life, plasma norepinephrine, autonomic dysfunction
- MeSH terms
- Ivabradine, Adult, Cardiovascular Agents, Double-Blind Method, Female, Heart Rate, Humans, Male, Norepinephrine, Quality of Life, Cross-Over Studies, Postural Orthostatic Tachycardia Syndrome
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