An increase in cardiovascular events (cardiovascular death and non-fatal myocardial infarction) has been shown in studies of patients prescribed ivabradine for angina with CCS grade II or higher. Reports of cardiac adverse events related to ivabradine received by the Therapeutic Goods Administration reflect the demonstrated increase in risk of 1%, which was considered to be significant, enough to update the product information.
Ivabradine is used to prevent symptoms in angina by selective inhibition of the sinoatrial node. However, these adverse events appear to be related to low resting heart rates. Angina patients must now have a resting heart rate of at least 70bpm before initiating treatment (formerly 60bpm). This should be monitored periodically with treatment discontinued if the heart rate drops below 50bpm or symptomatic bradycardia persists despite dose reduction.
Ivabradine should not be taken with potent CYP-450 inhibitors or moderate CYP-450 inhibitors with heart rate lowering properties (including verapamil and diltiazem). Also, the consumption of grapefruit juice should be avoided.
- Coralan® (ivabradine) Australian approved product information. Melbourne: Servier Laboratories. Approved 31 October 2006, amended 23 December 2013.
- Fox K, Ford I, Gabriel Steg P, Tardif J, Tendera M, Ferrari R. Ivabradine in Stable Coronary Artery Disease without Clinical Heart Failure. New Eng J Med. 2014; 371: 1091-9.
- Therapuetic Goods Administration. Ivabradine (Coralan). Canberra: Therapuetic Goods Administration; 2015.