Implications of EMA’s Pharmacovigilance Risk Assessment Committee statement on ivabradine inclusion within ESC guidelines and ivabradine prescribing recommendations

27 November 2014. As a result of new data from the SIGNIFY study (1), presented at ESC Congress 2014 and published simultaneously in the New England Journal of Medicine,  the EMA’s Pharmacovigilance Risk Assessment Committee (PRAC) has made recommendations aimed at reducing the risk of heart problems, including MI (heart attack) and bradycardia (slow heart rate) in patients prescribed ivabradine for angina (2).

The PRAC recommendations have been endorsed by the EMA’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.

The ESC leadership and guidelines chairs have reviewed the PRAC recommendations in the context of all the current ESC guidelines that include mention of ivabradine. No revision of ESC guidelines is required since the EMA has not changed any of the indications for ivabradine, only specific prescribing information.

A link to the EMA statement outlining the revised prescribing guidelines for ivabradine for the treatment of angina will be added to the ESC guidelines webpage and the EHJ website.

The new EMA prescribing information for ivabradine for the treatment of angina is as follows:

• Ivabradine should only be started if the patient’s resting heart rate is at least 70 beats per minute
• Because the new data from the SIGNIFY study did not show ivabradine provided benefits such as reducing the risk of heart attack or cardiovascular death (death due to heart problems) in patients with angina, ivabradine should only be used to alleviate symptoms of angina
• The starting dose of ivabradine for angina should not exceed 5 mg twice a day and the maximum dose should not exceed 7.5 mg twice a day
• Physicians should consider stopping ivabradine treatment if there is no improvement in angina symptoms after 3 months, or if the improvement is only limited
• Physicians must not prescribe ivabradine together with either verapamil or diltiazem, which both reduce heart rate
• Physicians should monitor any patient prescribed ivabradine for signs of 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 ivabradine treatment should be carefully reconsidered.
• Healthcare professionals will be notified by the EMA.