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Ivabradine: best avoided in stable angina

FEATURED REVIEW Ivabradine has been approved in Europe for second-line treatment of stable angina. In trials, ivabradine was no more effective than the comparators in preventing angina attacks. For long-term preventive treatment it is better to use better-documented treatments: a betablocker, or, if a betablocker cannot be used, verapamil or amlodipine.
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Abstract

  • The first-line symptomatic treatment for stable angina is a betablocker such as atenolol. Some calcium channel blockers such as verapamil, and the potassium channel agonist amlodipine, are second-line alternatives. Long-acting nitrate derivatives have poorly documented efficacy but can be used as adjuvants or as thirdline treatments.
  • Ivabradine is derived from verapamil but appears to have a different mechanism of action, mainly lowering the heart rate. It was approved for sale in Europe through the centralised procedure for second-line treatment of stable angina.
  • Clinical evaluation of ivabradine only includes randomised controlled trials versus two other anti-angina drugs: atenolol and amlodipine. Three double-blind randomised controlled trials lasting 3 to 4 months, based on surrogate exercise endpoints, failed to show that ivabradine was any more effective than atenolol or amlodipine, or even more effective than placebo in patients already treated with amlodipine.
  • In two one-year double-blind randomised controlled trials comparing ivabradine with atenolol or amlodipine in a total of 704 patients, ivabradine was no more effective than the comparators in preventing angina attacks.
  • In head-to-head comparisons, serious coronary events were significantly more frequent with ivabradine than with atenolol (3.8% versus 1.5%). Severe arrhythmias were also more frequent with ivabradine than with atenolol (1.3% versus 0.7%) or amlodipine (0.6% versus 0.2%).
  • Ivabradine provokes phosphenes (flashing lights, etc.) in about 17% of patients in the short term. Information is inadequate to assess possible risks of retinal toxicity in the long term.
  • Ivabradine is metabolised by cytochrome P450 isoenzyme CYP 3A4; there is therefore a potentially high risk of pharmacokinetic interactions.