Ivabradine (Procoralan) in the symptomatic treatment of angina: risk of cardiac side effects—new advice to minimise risk

Summary
Ivabradine may be associated with the risks of bradycardia, atrial fibrillation, and other cardiovascular risks.
Only start ivabradine if the resting heart rate is at least 70 beats per minute. Do not prescribe ivabradine with other medicines that cause bradycardia. Monitor patients regularly for atrial fibrillation and consider stopping ivabradine if there is only limited symptom improvement after 3 months

Ivabradine (Procoralan) is used to treat chronic heart failure and the symptoms of chronic angina in adults unsuited to or unable to take beta blockers. It can also be used in combination with beta-blockers in patients for whom an optimal beta-blocker dose is not enough.

The SIGNIFY clinical trial, included a pre-specified subgroup analysis of 12,049 participants who had symptomatic angina.
In this subgroup, there was a small but significant increase in the combined risk of cardiovascular death or non-fatal heart attack with ivabradine compared with placebo (3.4% vs 2.9% yearly incidence rates). The risk of bradycardia (17.9% vs 2.1%) and atrial fibrillation (5.3% vs 3.8%) was also increased in participants taking ivabradine compared with placebo.
Participants in the study were given higher doses of ivabradine than currently recommended in clinical practice. However, this did not fully explain the findings.

New advice for healthcare professionals:

When using ivabradine to treat the symptoms of chronic angina:

only start ivabradine if the resting heart rate is at least 70 beats per minute
do not prescribe ivabradine with other medicines that cause bradycardia, such as verapamil, diltiazem, or strong CYP3A4 inhibitors
monitor patients regularly for atrial fibrillation.
If atrial fibrillation occurs, carefully reconsider whether the benefits of continuing ivabradine treatment outweigh the risks
consider stopping ivabradine if there is no or only limited symptom improvement after 3 months

We also remind you of the following:
ivabradine is indicated to treat symptoms of chronic angina in patients unable to tolerate or with a contraindication to beta-blockers. It can also be used in combination with beta-blockers in patients for whom an optimal beta-blocker dose is not enough
the recommended starting dose is 5 mg twice daily
do not exceed the maximum maintenance dose of 7.5 mg twice daily
down-titrate the dose if resting heart rate decreases persistently below 50 beats per minute or if the patient experiences symptoms of bradycardia. The dose can be down-titrated to 2.5 mg twice daily if necessary
stop ivabradine treatment if the resting heart rate remains below 50 beats per minute or symptoms of bradycardia persist.

UK-MEDICINES HEALTH REGULATORY AGENCY-DEC 2014.

G MOHAN.