Lowering heart rate with Servier’s Procoralan appears to significantly reduce the risk of myocardial infarction and revascularisation surgery in a subgroup of patients with coronary artery disease and left ventricular dysfunction, and a heart rate of more than 70 beats per minutes.

However, the results, which were reported at the European Society of Cardiology congress in Munich, also showed that there was no advantage for Procoralan (ivabradine) on BEAUTIFUL’s primary endpoint of the composite of cardiovascular death, hospital admission for acute MI or hospital admission for new or worsening heart failure. BEAUTIFUL randomised nearly 11,000 patients already receiving recommended drug therapy to either Procoralan 5mg (increased to 7.5mg if needed) or placebo.

Lead investigator Kim Fox of the Royal Brompton Hospital, London, commented:“The study failed on its primary endpoint and so any conclusions are hypothesis-generating. However, in terms of ivabradine’s primary indication for chronic stable angina, the drug can certainly be safely used with a beta blocker.”

Prof Fox added: “There is already ample evidence that ivabradine is anti-anginal and the revascularisation outcome will further support this. The results for fatal and non-fatal MI are reassuring, but not definitive.”

Although BEAUTIFUL will not change treatment guidelines for patients with left-ventricular dysfunction, there may well be an increased interest in heart rate. Not only is this easy to check by taking the pulse, but BEAUTIFUL also clearly showed that resting heart rate over 70 bpm significantly increases cardiovascular risk in the types of patient included in the study. This could be an advantage for Procoralan since, unlike beta blockers, it lowers heart rate without reducing blood pressure and causing side-effects like fatigue.

Procoralan’s role in patients with moderate to severe heart failure and higher heart rate is currently being tested in SHIFT. Over 80% of BEAUTIFUL patients had mild to moderate heart failure and in retrospect the study might have been more positive if it had recruited patients with CAD without left-ventricular dysfunction. The same group of investigators are now planning a further study, SIGNIFY, to investigate Procoralan’s role in the treatment of these patients. By Sue Lyon in Munich