EMA recommends measures to reduce risk of heart problems with Corlentor/Procoralan (ivabradine)
The European Medicines Agency (EMA) has completed a review of Corlentor/Procoralan (ivabradine) and has made recommendations aimed at reducing the risk of heart problems, including heart attack and bradycardia (excessively low heart rate), in patients taking the medicine for angina. Corlentor/Procoralan is used to treat symptoms of angina (chest pain due to problems with the blood flow to the heart) and to treat heart failure.
When used for angina, Corlentor/Procoralan should only be started if the patient’s resting heart rate is at least 70 beats per minute (bpm). Because Corlentor/Procoralan has not been shown to provide benefits such as reducing the risk of heart attack or cardiovascular death (death due to heart problems), the medicine should only be used to alleviate symptoms of angina. Doctors should consider stopping treatment if there is no improvement in angina symptoms after 3 months, or if the improvement is only limited.
Other recommendations are that doctors must not prescribe Corlentor/Procoralan together with the medicines verapamil or diltiazem that reduce the heart rate, and that they should monitor their patients for atrial fibrillation (irregular rapid contractions of the upper chambers of the heart). If atrial fibrillation develops during treatment, the balance of benefits and risks of continued Corlentor/Procoralan treatment should be carefully reconsidered.
These recommendations are based on the EMA’s review of the final data from the SIGNIFY study, which showed that in a subgroup of patients who had symptomatic angina there was a small but significant increase in the combined risk of cardiovascular death or non-fatal heart attack with Corlentor/Procoralan compared with placebo (3.4% vs 2.9% yearly incidence rates). The data also indicated a higher risk of bradycardia with Corlentor/Procoralan compared with placebo (17.9% vs. 2.1%).
In its evaluation the EMA also assessed additional data on the safety and effectiveness of Corlentor/Procoralan which showed that the risk of atrial fibrillation is increased in patients treated with Corlentor/Procoralan compared with controls (4.9% vs 4.1%). In the SIGNIFY study, atrial fibrillation was observed in 5.3% of patients taking Corlentor/Procoralan compared with 3.8% in the placebo group.
Patients in the SIGNIFY study were started on a higher than recommended dose of Corlentor/Procoralan and received up to 10 mg twice a day, which is higher than the currently authorised maximum daily dose (7.5 mg twice a day). The EMA considered that the higher dose used in the study did not fully explain the findings. However, the Agency reiterated that the starting dose for angina should not exceed 5 mg twice a day and that the maximum dose should not exceed 7.5 mg twice a day.
The review of Corlentor/Procoralan was first carried out by the EMA’s Pharmacovigilance Risk Assessment Committee (PRAC). The PRAC recommendations have now been endorsed by the Agency’s Committee for Medicinal Products for Human Use (CHMP) in its final opinion. The CHMP opinion will be sent to the European Commission, which will issue a legally binding decision valid throughout the EU in due course.
Posted on the EMA website on 21 November 2014