The American Food and Drug Administration (FDA) has granted ivabradine marketing authorisation in the treatment of chronic heart failure (CHF), due to reduced left ventricular ejection fraction (LVEF). Ivabradine is a selective If-inhibitor and is indicated for CHF patients who have HF symptoms that are stable, a normal heartbeat with a resting heart rate of at least 70 beats per minute (bpm) and who are also taking beta blockers at the highest tolerable dose.

Ivabradine was reviewed under the FDA’s priority review program, which provides for an expedited review of drugs that are intended to treat a serious disease or condition and may provide a significant improvement over available therapy. It was also granted fast track designation, which helps facilitate the development and expedite the review of drugs to treat serious or life-threatening conditions and fill an unmet medical need.

Ivabradine had already been approved in Europe for treatment of patients with stable symptomatic HF (NYHA II-IV) with LVEF ≤35% and resting heart rate of >75 bpm, in addition to standard treatment including beta-blockers, unless contra-indicated or not tolerated. Its use is recommended in the HF guidelines of the European Society of Cardiology (ESC). Ivabradine is furthermore registered in Europe for symptomatic treatment of chronic stable angina pectoris in adults with coronary heart disease with normal sinus rhythm and heart rate >70 bpm, when inadequately controlled with an optimal dose of bètablockers or in case of contra-indication for beta-blockers or intolerance.

 “The U.S. registration of ivabradine has been obtained on the basis of trials conducted by Servier, in particular the SHIFT study in HF patients. SHIFT was carried out in 37 countries”, pointed out Isabelle Tupinon-Mathieu, Director of Servier’s Cardiovascular and Metabolism Innovation Centre, Vice-President of Research and Development. In the SHIFT study, ivabradine reduced the time to first occurrence of hospitalization for worsening HF compared to placebo. The most common side effects observed in clinical trial participants were bradycardia, hypertension, atrial fibrillation, and temporary vision disturbance (flashes of light).

The FDA followed the ESC HF guideline in adopting a threshold of HR>70 bpm, as opposed to the >75bpm that the European Medicines Agency chose. At a resting heart rate of >70bpm, ivabradine not only gives a significant reduction of CV mortality and HF hospitalisation, but also a reduction of total mortality.
 Press releases Servier April 16 2015 and FDA April 15 2015