a-t 2017; 48: 54

Prescription restrictions for ivabradine (PROCORALAN) in France: In 2014 the European Medicines Agency (EMA) re-evaluated the risk benefit ratio of ivabradine (PROCORALAN, in IMPLICOR; a-t 2006; 37: 17-9) on the basis of the results of the SIGNIFY study (1). In this large randomised study of more than 19,000 patients with stable coronary heart disease the F ion channel blocker, which is authorised for the symptomatic treatment of angina pectoris and chronic heart failure, was not able to demonstrate any advantages compared to placebo in terms of the primary endpoint, a combination of cardiovascular death and non-fatal heart attack (6.8% versus 6.4%, hazard ratio [HR] 1.08; 95% confidence interval [CI] 0,96-1,20). In the predefined sub-group of patients with symptomatic angina pectoris (n = 12.049) ivabradine even performed significantly worse than placebo (HR 1.18; 95% CI 1.03-1.35; a-t 2014; 45: 62). It also caused significantly more bradycardia (18.0% vs. 2.3%) and atrial fibrillation (5.3% vs. 3.8%) (1). In order to decrease the risk of cardiovascular events and severe bradycardia since then it has been recommended among other things that patients with chronic stable angina pectoris have their heart rate checked multiple times using repeated measurements, an ECG or 24-hour outpatient monitoring before the start of treatment or a planned increase in dose. Regular clinical monitoring is also advised for the occurrence of atrial fibrillation. Ivabradine should be discontinued (2,3) if the angina pectoris symptoms do not improve within three months. In France, they are going one step further now: since January 2017 the first prescription of ivabradine and the first prescription of each year must be issued by a cardiologist. In addition to this, the cardiologist should check the treatment effect at least once a year and is also responsible for the necessary controls of the heart rate before a planned increase in dose (4). The French drug authorities, who already advocated stricter restrictions in the European risk assessment procedures in 2014 (5), justify these measures on the basis of ivabradine being prescribed too often (4). The French Pharmacovigilance Committee had previously also called the number of prescriptions by general practitioners "concerning" and requested to limit the prescription of the drug to cardiologists (6). We still feel that there is no indication for ivabradine, -Ed.