Ivabradine reduces MI in patients with LVD
Ivabradine has been found to reduce admission rates for MI and coronary revascularisation in patients with a heart rate ?70bpm when used in addition to standard care.
The BEAUTIFUL trial was designed to assess the impact of ivabradine on cardiac outcomes in patients with coronary disease and LV dysfunction. The study recruited 10,917 patients from 33 countries, who were randomised to ivabradine or placebo in addition to best medical therapy, which included aspirin, ACE inhibitors and beta-blockers. Patients were followed up for a median of 19 months. The primary endpoint was a composite of cardiovascular death and admission for acute MI or new onset/worsening heart failure.
There was no significant difference in the primary endpoint between the two groups (HR 1.00, 95% CI 0.91-1.1, P=0.94). However, ivabradine did reduce admission rates for MI and coronary revascularisation in a subgroup of patients with a heart rate ? 70bpm at baseline (HR 0.64, 95% CI 0.49-0.84, P=0.001 and HR 0.70, 95% CI 0.52-0.93, P=0.016 respectively), although there was no significant difference in the primary endpoint in these patients. It is worth noting that fewer patients used beta-blockers in the higher heart rate group compared with the total study population (84% compared with 87%) and this may have influenced the observed benefit of ivabradine in this subgroup.
The study found that ivabradine was well tolerated, with few side-effects with the exception of bradycardia.
Ivabradine is a new anti-anginal drug that works by blocking transmembrane proteins responsible for the slow membrane current that triggers cardiac electrical activity. This allows control of heart rate without influencing other parameters, such as the force of contraction, and the drug is reported to have few side-effects compared with traditional rate-limiting drugs such as beta-blockers. The association between higher heart rates and poor outcomes in ischaemic heart disease has been well described.
Although the trial found no significant difference in its primary endpoint, I would suggest that ivabradine has a place in managing chronic stable angina when beta-blockers are not tolerated or cannot be titrated to an effective dose. Whether it will be preferred in place of a rate-limiting calcium antagonist is open to debate.
Fox K, Ford I, Steg PG et al. Ivabradine for patients with stable coronary artery disease and left-ventricular systolic dysfunction (BEAUTIFUL): a randomised, double-blind, placebo-controlled trial. Lancet 2008;372:807-16Reviewer
Dr Peter Savill
GPwSI Cardiology, Southampton