IVABRADINE DID NOT DO WELL IN SIGNIFY.

I must say that nowadays, at clinical meeting, we are hearing reported, more negative trials.
In the recently concluded European Society of Cardiology Annual Scientific Congress,, one such trial reported was the SIGNIFY trial. This trial was to a randomised, double blinded, placebo control trial to test the benefits of Ivabradine against the placebo in patients with stable angina pectoris, without heart failure and worse heart rate was greater than 70 beats per minute. Ivabradine was a heart rate slowing drug working through the If  channel n the SA node. I suppose the investigators were hoping to show that by slowing the heart rate from 70 to 60 per minute, it would make a better outcome. The PI was Dr Kim Fox of London. The paper was also published simultaneously in the New England Journal of Medicine 371:1091, 2014. They managed to enrol 19,102 patients who had stable coronary disease without heart failure and whose heart rate was more than 70 / min. It is important to note that of the 19,000 or so patients, 12,000 or so had class 2 angina or more ( Canadian classification ). The primary endpoint was CVS mortality and non fatal MI. Half the patients were given Ivabradine and the other half, a placebo.

After 27 months of follow-up. it was true that the Heart Rate was lower in the treated arm. There was however no significant difference in the primary endpoint. But in the 12,000 patients with Canadian class 2 or more angina, there were more deaths and non fatal MI. There also seemed to be a higher incidence of atrial fibrillation in the treated arm.

Now, this last two points have given rise to some concern. We now know ( 19,000 is a large number ) that there is no point using ivabradine in patients with stable angina pectoris without heart failure. Secondly, we have to be careful in those with Class 2 or more angina, as it may do harm. Why? we are not certain.