Randomized Trial of Ivabradine in Patients With Hyperadrenergic Postural Orthostatic Tachycardia Syndrome - Ivabradine in POTS

Contribution To Literature:

The Ivabradine in POTS trial showed that ivabradine was superior to placebo at improving heart rate and quality of life among patients with hyperadrenergic POTS.


The goal of the trial was to evaluate ivabradine compared with placebo among patients with postural orthostatic tachycardia syndrome (POTS). Ivabradine is a selective blocker of the Ifunny channel of the sinoatrial node that does not lower blood pressure.

Study Design

  • Randomized
  • Parallel
  • Blinded
  • Crossover

Patients with hyperadrenergic POTS were randomized to ivabradine twice daily (n = 22) versus placebo (n = 22). Subjects were started on either ivabradine or placebo for 1 month, followed by a 1-week washout period, then crossed over to the other treatment for 1 month.

  • Total number of enrollees: 22
  • Duration of follow-up: 2.5 months
  • Mean patient age: 33.9 years
  • Percentage female: 95.5%

Inclusion criteria:

  • Patients 18-65 years of age with hyperadrenergic POTS
  • Plasma norepinephrine level >600 pg/ml and abnormal tilt table test (heart rate ≥30 bpm)

Exclusion criteria:

  • Resting heart rate <60 bpm
  • Atrial fibrillation
  • Supraventricular tachycardia
  • Pregnant and/or breast-feeding women

Other salient features/characteristics:

  • Norepinephrine (supine), 514 pg/ml; norepinephrine (standing), 1143 pg/ml
  • Heart rate (supine), 77 bpm; heart rate (standing), 101 bpm

Principal Findings:

The primary outcome, change in heart rate (standing vs. supine) at 1 month, was 13.1 bpm in the ivabradine group compared with 17.0 bpm in the placebo group (p = 0.001).

Secondary outcomes:

  • Quality of life measures of physical functioning (p = 0.008) and social functioning (p = 0.021) improved with ivabradine compared with placebo.
  • Change in norepinephrine (standing vs. supine) at 1 month was 442 pg/ml in the ivabradine group compared with 532 pg/ml in the placebo group (p = 0.056).


Among patients with hyperadrenergic POTS, ivabradine was associated with an improvement in heart rate and some quality of life measures (physical functioning and social functioning). Standing norepinephrine levels were also marginally improved with ivabradine. There are currently no Class I recommendations for the treatment of this challenging condition. Although this was a small trial, the use of ivabradine for this challenging condition seems reasonable.


Taub PR, Zadourian A, Lo HC, Ormiston CK, Golshan S, Hsu JC. Randomized Trial of Ivabradine in Patients With Hyperadrenergic Postural Orthostatic Tachycardia Syndrome. J Am Coll Cardiol 2021;77:861-71.

Editorial Comment: Raj SR, Sheldon RS. Higher Quality Evidence to Guide Our Management of Postural Orthostatic Tachycardia Syndrome: A New Era? J Am Coll Cardiol 2021;77:872-4.

Clinical Topics: Arrhythmias and Clinical EP, Dyslipidemia, Prevention, Implantable Devices, EP Basic Science, SCD/Ventricular Arrhythmias, Atrial Fibrillation/Supraventricular Arrhythmias, Lipid Metabolism

Keywords: Arrhythmias, Cardiac, Blood Pressure, Heart Rate, Hypotension, Benzazepines, Norepinephrine, Norepinephrine Plasma Membrane Transport Proteins, Postural Orthostatic Tachycardia Syndrome, Quality of Life, Secondary Prevention, Sinoatrial Node, Tachycardia, Tilt-Table Test

< Back to Listings