Clinical Efficacy of Ivabradine in Patients With Inappropriate Sinus Tachycardia
Open accessAbstract
Objectives The purpose of this study was to investigate the role of ivabradine in the treatment of symptomatic inappropriate sinus tachycardia using a double-blind, placebo-controlled, crossover design.Background Due to its I(f) blocking properties, ivabradine can selectively attenuate the high discharge rate from sinus node cells, causing inappropriate sinus tachycardia.Methods Twenty-one patients were randomized to receive placebo (n=10) or ivabradine 5 mg twice daily (n=11) for 6 weeks. After a washout period, patients crossed over for an additional 6 weeks. Each patient underwent symptom evaluation and heart rate assessment at the start and finish of each phase.Results After taking ivabradine, patients reported elimination of >70% of symptoms (relative risk: 0.25; 95% CI: 0.18 to 0.34; p<0.001), with 47% of them experiencing complete elimination. These effects were associated with a significant reduction of heart rate at rest (from 88±11 beats/min to 76±11 beats/min, p=0.011), on standing (from 108±12 beats/min to 92±11 beats/min, p<0.0001), during 24 h (from 88±5 beats/min to 77±9 beats/min, p=0.001), and during effort (from 176±17 beats/min to 158±16 beats/min, p=0.001). Ivabradine administration was also associated with a significant increase in exercise performance. No cardiovascular side effects were observed in any patients while taking ivabradine.Conclusions In this cohort, ivabradine significantly improved symptoms associated with inappropriate sinus tachycardia and completely eliminated them in approximately half of the patients. These findings suggest that ivabradine may be an important agent for improving symptoms in patients with inappropriate sinus tachycardia.
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The strongest evidence for ivabradine in IST comes from a small randomized crossover study of 21 patients assigned to placebo or ivabradine 5 mg twice daily for 12 weeks.
“The strongest evidence to date comes from a small, randomized crossover study in which 21 patients with IST were randomized to placebo or ivabradine 5 mg twice daily for a total of 12 weeks.63”
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 [63]
The Results report 21 enrolled patients, and Study design describes a randomized placebo-controlled crossover trial with two six-week treatment phases separated by a seven-day washout. Ivabradine started at 5 mg twice daily, but Effects of ivabradine on symptoms and HR reports that the dose was increased in 11 patients and decreased in two; 5 mg twice daily was therefore not the fixed dose throughout. (LLM, conf=0.88)
Experimental — accuracy not yet measuredIvabradine eliminated symptoms in 70% of IST patients and increased exercise performance.
“Ivabradine eliminated symptoms in 70% of patients and increased exercise performance.”
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 [63]
The Discussion and Conclusions (pp. 1327–1329) say ivabradine eliminated more than 70% of baseline symptoms, not all symptoms in 70% of patients. The Results (p. 1325) report complete symptom elimination in 9 of 21 patients, while exercise duration and capacity increased with ivabradine. Thus the exercise-performance finding is supported, but the claim confuses the percentage of symptoms eliminated with the percentage of patients whose symptoms were eliminated. (LLM, conf=0.92)
Experimental — accuracy not yet measuredIvabradine is usually regarded as an alternative to beta-blockers in POTS.
“It is usually seen as an alternative to beta-blockers.”
From Postural orthostatic tachycardia syndrome: clinical presentation, aetiology and management (2019) · cites this paper as [89]
Ivabradine is a selective If current blocker that slows heart rate without affecting intraventricular conduction, contractility, or haemodynamics, and has been found safe and effective in multiple small trials.
“ivabradine, a selective If current blocker that directly slows the HR without influence on intraventricular conduction, contractility, or haemodynamics, has been found safe and effective in multiple small trials (Table 9).85,86”
From European Heart Rhythm Association (EHRA) consensus document on the management of supraventricular arrhythmias, endorsed by Heart Rhythm Society (HRS), Asia-Pacific Heart Rhythm Society (APHRS), and Sociedad Latinoamericana de Estimulacion Cardiaca y Electrofisiologia (SOLAECE) (2017) · cites this paper as [85]
Ivabradine has been associated with increased tolerance of physical exercise in IST.
“This treatment has been also associated with an increased tolerance of physical exercise.”
From European Heart Rhythm Association (EHRA) consensus document on the management of supraventricular arrhythmias, endorsed by Heart Rhythm Society (HRS), Asia-Pacific Heart Rhythm Society (APHRS), and Sociedad Latinoamericana de Estimulacion Cardiaca y Electrofisiologia (SOLAECE) (2017) · cites this paper as [85]
In a double-blind randomized placebo-controlled crossover trial of 21 patients, ivabradine eliminated 75% of IST-related symptoms, with nearly 50% experiencing prompt complete resolution in short-term follow-up.
“In a double-blind, randomized, placebo-controlled trial with a crossover design on 21 patients, 75% of inappropriate sinus tachycardia-related symptoms were eliminated in the ivabradine cohort, with nearly 50% of patients experiencing prompt and complete resolution of all symptoms in a short-term follow-up.85”
From European Heart Rhythm Association (EHRA) consensus document on the management of supraventricular arrhythmias, endorsed by Heart Rhythm Society (HRS), Asia-Pacific Heart Rhythm Society (APHRS), and Sociedad Latinoamericana de Estimulacion Cardiaca y Electrofisiologia (SOLAECE) (2017) · cites this paper as [85]
Exercise training has proven effective for physical reconditioning and lessening episodes of sinus tachycardia triggered by hemodynamic, postural, and/or physical stressors in patients with autonomic nervous system conditions and no underlying familial or personal history of heart disease.
“Similarly, exercise training has also proven effective for physical reconditioning and lessening episodes of sinus tachycardia triggered by hemodynamic, postural, and/or physical stressors in patients with autonomic nervous system conditions and no underlying familial or personal history of heart disease49,185,192,195,196.”
From Sinus Tachycardia: a Multidisciplinary Expert Focused Review (2022) · cites this paper as [195]
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- Authors
- Cappato, R., Castelvecchio, S., Ricci, C., Bianco, E., Vitali-Serdoz, L., Gnecchi-Ruscone, T., Pittalis, M., De Ambroggi, L., Baruscotti, M., Gaeta, M., Furlanello, F., Di Francesco, D., & Lupo, P. P.
- Affiliations
- IRCCS Policlinico San Donato (IT)
- Don Carlo Gnocchi Foundation (IT)
- University of Pavia (IT)
- Corresponding author
- Cappato, Riccardo
- Venue
- Journal of the American College of Cardiology
- Publisher
- Elsevier BV
- Published
- 2012-10
- Volume
- 60
- Issue
- 15
- Pages
- 1323-1329
- ISSN
- 0735-1097 (ISSN-L)
- OpenAlex
- W2270618117
- Semantic Scholar
- fdfeb8c10c39535d25e56b18c898deeff8d02606
- Cited by
- 159
- References
- 21
- Citations by year
- 2026: 4 · 2025: 9 · 2024: 9 · 2023: 6 · 2022: 8 · 2021: 17 · 2020: 13 · 2019: 10 · 2018: 9 · 2017: 10 · 2016: 13 · 2015: 24 · 2014: 10 · 2013: 15 · 2012: 1
- FWCI
- 10.29
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of the American College of Cardiology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart rate and cardiovascular health
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Rate Variability and Autonomic Control
- Keywords
- ivabradine, inappropriate sinus tachycardia, sinoatrial node, heart rate reduction, symptom relief, exercise performance
- MeSH terms
- Ivabradine, Administration, Oral, Adult, Benzazepines, Dose-Response Relationship, Drug, Double-Blind Method, Drug Administration Schedule, Electrocardiography, Female, Follow-Up Studies, Heart Rate, Humans, Male, Prospective Studies, Sinoatrial Node, Tachycardia, Sinus, Treatment Outcome, Cross-Over Studies, Cyclic Nucleotide-Gated Cation Channels
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