Randomized trial of ivabradine in patients with hyperadrenergic postural orthostatic tachycardia syndrome

Taub, Pam R.; Zadourian, Adena; Lo, Hannah C.; Ormiston, Cameron K.; Golshan, Shahrokh; Hsu, Jonathan C.

doi:10.1016/j.jacc.2020.12.029

Cited by 122Cardiovascular Syncope and Autonomic DisordersHeart Rate Variability and Autonomic ControlHeart rate and cardiovascular health

Randomized trial of ivabradine in patients with hyperadrenergic postural orthostatic tachycardia syndrome

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Taub, Pam R., Zadourian, Adena, Lo, Hannah C., Ormiston, Cameron K., Golshan, Shahrokh, Hsu, Jonathan C.·2021·Journal of the American College of Cardiology

DOI 10.1016/j.jacc.2020.12.029

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Abstract

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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One randomized placebo-controlled trial examining ivabradine demonstrated a significant reduction in heart rate compared to placebo.
“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]
Both ivabradine and propranolol significantly reduced the orthostatic heart rate increase compared to placebo.
“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]
A limited number of prior studies have examined the effects of propranolol or ivabradine on POTS.
“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]
Ivabradine selectively blocks the If channels in the sinoatrial node, lowering heart rate directly without impacting other systemic functions like blood pressure.
“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 that randomized trial, all patients were of the hyperadrenergic subtype and had elevated baseline norepinephrine levels.
“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]

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Taub, P. R., Zadourian, A., & Hsu, J. C. (2021) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2021.04.046
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Ivabradine as a Treatment for Postural Orthostatic Tachycardia Syndrome: A Systematic Review
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Abstract 4144538: Ivabradine in Patients With Postural Orthostatic Tachycardia Syndrome: A Single-Arm Systematic Review and Meta-analysis
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Ivabradine in the treatment of postural tachycardia syndrome (POTS), a single center experience
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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.
ORCID: Taub, Pam R.
Lo, Hannah C.
Ormiston, Cameron K.
Hsu, Jonathan C.
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)
DOI: 10.1016/j.jacc.2020.12.029
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: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 387 d)
Locations: Journal of the American College of Cardiology (publishedVersion)
PubMed (publishedVersion)
Funders: Amgen
Topics: Health Sciences › Medicine › Surgery › 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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Randomized trial of ivabradine in patients with hyperadrenergic postural orthostatic tachycardia syndrome

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