Randomized Trial of Ivabradine in Patients With Hyperadrenergic [POTS], 2021, Taub et al

Ryan31337 · Feb 18, 2021

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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Paywall, https://www.jacc.org/doi/full/10.1016/j.jacc.2020.12.029

Ryan31337 · Feb 18, 2021

Pleased to see some higher quality evidence for use of Ivabradine in POTS.

Its been prescribed by the experts for years, I have been taking it since 2016 with good results.

I'm glad to see some acknowledgment of it lowering NE levels too - something that is rarely mentioned in the literature but has been very clear to me as a patient. Most descriptions of Ivabradine go the other way, suggesting its highly selective and only affects heart rate. The only references I ever found to it having an impact on stress hormones were some animal studies and one human study, where it was used in surgical procedures. It has a profound effect reducing the "wired but tired" sensations for me.

The editorial comment from Raj is interesting too:
Higher Quality Evidence to Guide Our Management of Postural Orthostatic Tachycardia Syndrome: A New Era?
https://www.jacc.org/doi/10.1016/j.jacc.2020.12.028

Hutan · Jun 7, 2021

Thanks for posting this @Ryan31337.

I haven't read the paper itself, but it does look like a nice study, and the editorial is indeed interesting.

the editorial said:

Taub et al. (1) are to be complimented for conducting this important study. This study will likely be cited in the next iteration of POTS scientific statements. Let us hope that this is just the beginning of a new era of rigorous, controlled, and at least modestly long clinical trials that provide high-quality evidence to guide the management of patients with POTS.
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It would be great to get some trials done in people with ME/CFS with strong orthostatic intolerance symptoms.

Ryan31337 · Jun 8, 2021

Hutan said: ↑

It would be great to get some trials done in people with ME/CFS with strong orthostatic intolerance symptoms.
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Waiting very impatiently for this: The Exercise Response to Pharmacologic Cholinergic Stimulation in Myalgic Encephalomyelitis / Chronic Fatigue Syndrome - Full Text View - ClinicalTrials.gov

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Randomized Trial of Ivabradine in Patients With Hyperadrenergic [POTS], 2021, Taub et al

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Randomized Trial of Ivabradine in Patients With Hyperadrenergic [POTS], 2021, Taub et al

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