August 31, 2008 (Munich, Germany) - Lowering heart rate with Ivabradine (Procoralan, Servier) does not improve cardiac outcomes for all patients with coronary artery disease (CAD) and left ventricular systolic dysfunction, results from the BEAUTIFUL (morBidity-mortality EvAlUaTion of the If inhibitor ivabradine in patients with coronary disease and left ventricULar dysfunction) trial suggest. But investigators showed here at the European Society of Cardiology Congress 2008, that Ivabradine ould be beneficial in patients with heart rates of 70 beats per minute (bpm) or higher.
This trial failed its primary end point in BEAUTIFUL, and the conclusions that we can draw regarding the reduction in fatal and nonfatal MI are to a great extent hypothesis generating," Dr Kim Fox (Brompton Hospital, UK) acknowledged in a morning press conference.
This randomised, double-blind, placebo-controlled, parallel-group trial recruited 10,917 CAD patients with LV ejection fraction <40%. Patients received ivabradine 5 mg, with the intention of uptitrating to 7.5 mg twice daily (n=5479) or placebo (n=5438) on top of recommended guidelines medication: antiplatelet agents (94%), angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (91%), ├Ä╦ø-blockers (87%), as well as lipid-lowering agents (76%).
The results showed treatment with ivabradine did not result in a significant reduction of the primary composite end point (Cardiovascular death, admission to hospital for acute MI and admission to hospital for heart failure). However in patients with baseline heart rate more than 70 bpm, ivabradine significantly reduced the risk of hospitalisation for fatal and non-fatal MI by 36% and the risk of coronary revascularisation by 30% compared with placebo. This study also confirms that ivabradine is safe and well tolerated and can be used with all routinely prescribed cardiovascular drugs.
Despite the failure to reduce cardiovascular death and hospital admissions, the BEAUTIFUL results constitute a step further in the management of these coronary patients with heart rate above 70 bpm. For the first time it has been shown that heart rate reduction with ivabradine further reduces coronary events even in patients receiving the current optimal cardiovascular therapy.