- Medicines and Healthcare products Regulatory Agency
- 19 December 2014
- Therapeutic area:
- Cardiovascular disease and lipidology
New advice to minimise risk
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 trial1 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
Article citation: Drug Safety Update volume 8 issue 5, December 2014: A1
Fox K et al. N Engl J Med. 2014 Sep 18;371(12):1091-9 ↩
Published: 19 December 2014
Therapeutic area: Cardiovascular disease and lipidology