The following are key points to remember about the clinical use of ivabradine:

1. Ivabradine is a drug with unique electrophysiological effects, best characterized by its negative chronotropic effect on the sinoatrial node.
2. The clinical use of ivabradine is predicated on its mechanism of action on sinoatrial nodal tissue where it selectively inhibits the funny current (I_f) and results in a decrease in heart rate.
3. It is distinct from other pharmacological agents known to have benefit in heart failure with reduced ejection fraction in that it does not target the neurohormonal system.
4. Ivabradine’s overall favorable safety profile can be attributed to electrophysiological actions that are limited to the sinoatrial node (inhibition of I_f) and the absence of clinically significant nonelectrophysiological effects.
5. The most common cardiovascular adverse reaction is bradycardia, which may result in symptoms such as dizziness and/or fatigue. A meta-analysis has also demonstrated a 15% increase in relative risk for atrial fibrillation.
6. The incidence of atrial fibrillation must, however, be considered and addressed, given its consequences, and may, in part, be related to ivabradine’s bradycardic effects in certain patient populations.
7. Ivabradine is best viewed by clinicians as a second-line drug for systolic heart failure and chronic stable angina, with the understanding that it has received different region-based approvals for patients with specific clinical profiles.
8. Ivabradine’s most frequent application in electrophysiology is for the treatment of inappropriate sinus tachycardia. It should be noted that its use for inappropriate sinus tachycardia is not an European Medicines Agency/Food and Drug Administration–approved indication for ivabradine.
9. Its role in the treatment of inappropriate sinus tachycardia and other electrophysiological disorders, although encouraging, lacks the support of large studies and currently remain unapproved indications.
10. Additional prospective and randomized evaluations are needed before recommending an expanded role for ivabradine.

Keywords: Angina, Stable, Arrhythmias, Cardiac, Atrial Fibrillation, Benzazepines, Bradycardia, Dizziness, Electrophysiology, Heart Failure, Heart Failure, Systolic, Heart Rate, Sinoatrial Node, Stroke Volume, Tachycardia, Sinus, Vertigo

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