Ivabradine: carefully monitor for bradycardia

Emerging clinical trial evidence of increased cardiovascular risk.

From:
Medicines and Healthcare products Regulatory Agency
Published
11 December 2014
Therapeutic area:
Cardiovascular disease and lipidology

Article date: June 2014

Ivabradine (Procorolan) is used to treat symptoms of long-term stable angina in adults with coronary heart disease who have a normal heart rhythm. Ivabradine is also used in patients with long-term heart failure who have a normal heart rhythm but whose heart rate is at least 75 beats per minute (bpm).

The SIGNIFY trial investigated the efficacy of ivabradine compared with placebo in people with coronary artery disease. The ivabradine dose regimen used in the trial (7.5 to 10 mg twice daily) was higher than the licensed posology (5 to 7.5 mg twice daily). The trial included a pre-specified subgroup analysis of participants with symptomatic angina of CCS class II or more. Preliminary results have shown a small but statistically significant increase in the combined risk of cardiovascular death and non-fatal myocardial infarction with ivabradine compared with placebo in this subgroup. This cardiovascular risk might be associated with a target heart rate below 60 bpm.

The European Medicines Agency is reviewing how the data from the SIGNIFY study impact the balance of benefits and risks of ivabradine. While the review is ongoing, we remind you of the following:

Advice for healthcare professionals:

Posology and monitoring

  • The starting dose of ivabradine is 5 mg twice daily. The maintenance dose should not exceed 7.5 mg twice daily.
  • Carefully monitor patients for bradycardia or its symptoms (eg, dizziness, fatigue, hypotension).
  • Down-titrate the dose if resting heart rate decreases persistently below 50 bpm 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 bpm or symptoms of bradycardia persist.
  • Only increase the dose to 7.5 mg twice daily after 3 to 4 weeks of treatment and if the 5 mg dose is well tolerated but insufficient. Carefully monitor the effect of a dose increase on heart rate.

Other considerations

  • Avoid concomitant use of ivabradine with heart rate-reducing calcium channel blockers such as verapamil or diltiazem.
  • Review the treatment of patients currently using ivabradine where appropriate.

Further information

European Medicines Agency statement 8 May 2014

Letter sent to healthcare professionals in June 2014 (111Kb)

Article citation: Drug Safety Update volume 7 issue 11, June 2014: S1.

Updates to this page

Published 11 December 2014
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