Ivabradine toxicity: a case report and review

Ivabradine is a unique antiarrhythmic drug that was designed to affect chronotropy with no effect on inotropy or lusitropy. It was first approved by the European Medicines Agency in 2005 for stable angina treatment, and then in 2009 the indication was expanded to include uncontrolled angina with heart rates ≥60 beats per minute (bpm) on optimal beta-blocker therapy.1 Based on the SHIFT – HF trial in 2011, it got accepted for use in patients with systolic heart failure with heart rate greater than 70 bpm on maximally tolerated beta-blocker therapy or who have contraindication(s) to beta-blockers.2 It got approved by the Food and Drug Administration (FDA) in 2015 for use in heart failure.1 The FDA did not recommend its use for angina in the United States because the use of ivabradine in coronary disease and angina did not improve outcomes based on the SIGNIFY trial.3 Ivabradine has been on the market for less than a decade in the United States and longer than that in Europe. As its use is expanded worldwide, cases of ivabradine toxidromes are likely to be common. Thus far there are only 3 reported cases of overdoses worldwide4, 5, 6 based on literature search. We report on a 19-year-old woman who was prescribed ivabradine for inappropriate sinus tachycardia and had acute ivabradine toxicity. This case report will add to our repertoire of knowledge on ivabradine toxicity and its pathophysiology in human subjects.