New EMA recommendations for the use of CORLENTOR/PROCORALAN

21/11/2014

 

Suresnes, 21 November 2014

The European Medicines Agency’s Committee for Medicinal Product for Human Use (CHMP) issued new recommendations for the use of Procoralan/Corlentor, aimed at reducing the risk of heart problems, including heart attack and bradycardia, at the end of the review procedure. The benefit-risk balance of the product remains positive for its authorized indications (symptomatic treatment of chronic stable angina pectoris and chronic heart failure).

This review was initiated in May 2014, following the results of the SIGNIFY study. In this trial, performed in coronary artery disease patients without left ventricular dysfunction, ivabradine did not affect primary composite end-point. A small but significant increase in the combined risk of cardiovascular death or non-fatal myocardial infarction was observed in a subgroup of patients with symptomatic angina (Canadian Cardiovascular Score class >2).  Of note, the SIGNIFY trial was performed with higher dose regimens than currently authorized. The risk of atrial fibrillation was increased in patients treated with ivabradine as compared to patients taking placebo, in the SIGNIFY study (5.3% vs 3.8%) and in additional data from a pooled analysis (4.9% vs 4.1%).

Hence, healthcare professionals should follow these recommendations: 

  • The data from SIGNIFY did not demonstrate a beneficial effect for Corlentor/Procoralan on cardiovascular outcomes in coronary artery patients without clinical heart failure. Its use is only beneficial for symptomatic treatment in patients with chronic stable angina pectoris who cannot be treated with beta-blockers, or in combination with beta-blockers in case their disease is not controlled with them alone.
  • In the symptomatic treatment of patients with chronic stable angina, Corlentor/Procoralan should only be started if the patient’s resting heart rate is above or equal to 70 beats per minute (bpm).
  • The starting dose of Corlentor/Procoralan should not exceed 5 mg twice daily and the maintenance dose of Corlentor/Procoralan should not exceed 7.5 mg twice daily.
  • Corlentor/Procoralan should be discontinued if the symptoms of angina do not improve within 3 months. In addition, discontinuation should be considered if the improvement is only limited and if there is no clinically relevant reduction in resting heart rate within 3 months.
  • The concomitant use of Corlentor/Procoralan with verapamil or diltiazem is now contraindicated.
  • Prior to starting treatment or when considering titration, serial heart rate measurements, ECG, or ambulatory 24-hour monitoring should be considered when determining the heart rate.
  • The risk of developing atrial fibrillation is increased in patients treated with Corlentor/Procoralan. Regular clinically monitoring for the occurrence of atrial fibrillation is recommended. If atrial fibrillation develops during treatment, the balance of benefits and risks of continued Corlentor/Procoralan treatment should be carefully reconsidered.
  • If, during treatment, the heart rate decreases below 50 bpm at rest or the patient experiences symptoms related to bradycardia, the dose must be decreased (the lowest dose is 2.5 mg twice daily). If, despite dose reduction, the heart rate remains below 50 bpm or symptoms of bradycardia persist, treatment must be discontinued. 

Servier will disseminate detailed information to healthcare professionals in countries where Corlentor/Procoralan is registered, specifying the agency’s recommendations and the practical implications for the management of their patients.

For further information, please refer to the EMA communication