The FDA on Wednesday approved ivabradine (Corlanor), Amgen’s new heart failure drug. The drug has been available for several years in Europe, where it is sold by Servier under the brand names of Corlentor and Procoralan.
Ivabradine was approved for the reduction of hospitalization from worsening heart failure. It is indicated for use in stable heart failure patients who are in sinus rhythm, have a resting heart rate of at least 70 bpm, and who are also taking the highest tolerable dose of a beta blocker. Ivabradine slows the rate of the heart by inhibiting the so-called “funny” current within the heart’s natural pacemaker, the sinoatrial node.
The funny current is an inward cation flux which helps initiate diastolic depolarization in pacemaker cells. So, if you inhibit the funny current heart rate slows. I have seen the FDA press release for consumers but not the product labeling. From the press release:
Corlanor is approved for use in certain people who have long-lasting (chronic) heart failure caused by the lower-left part of their heart not contracting well. The drug is indicated for patients who have symptoms of heart failure that are stable, a normal heartbeat with a resting heart rate of at least 70 beats per minute and are also taking beta blockers at the highest dose they can tolerate.
Reading between the lines it would appear that the drug is approved for patients with systolic dysfuction. The proviso concerning beta blockers, it would seem to me, will restrict the use of the drug, since many patients at the limits of beta blocker tolerance are there due to low heart rate. The niche for ivabradine may be in those patients at the limits of beta blocker tolerance for blood pressure reasons who still have a heart rate of at least 70.
An often forgotten fact is that heart rate reduction by itself is good for patients with heart failure. That was the premise of the the SHIFT study, the results of which are the basis of the drug's approval. From the Lancet paper:
Raised resting heart rate is a marker of cardiovascular risk. We postulated that heart rate is also a risk factor for cardiovascular events in heart failure. In the SHIFT trial, patients with chronic heart failure were treated with the selective heart-rate-lowering agent ivabradine. We aimed to test our hypothesis by investigating the association between heart rate and events in this patient population...
In the placebo group, patients with the highest heart rates (greater than or equal to 87 beats per min [bpm], n=682, 286 events) were at more than two-fold higher risk for the primary composite endpoint than were patients with the lowest heart rates (70 to less than 72 bpm, n=461, 92 events; hazard ratio [HR] 2·34, 95% CI 1·84–2·98, p less than 0·0001). Risk of primary composite endpoint events increased by 3% with every beat increase from baseline heart rate and 16% for every 5-bpm increase. In the ivabradine group, there was a direct association between heart rate achieved at 28 days and subsequent cardiac outcomes. Patients with heart rates lower than 60 bpm at 28 days on treatment had fewer primary composite endpoint events during the study (n=1192; event rate 17·4%, 95% CI 15·3–19·6) than did patients with higher heart rates. The effect of ivabradine is accounted for by heart-rate reduction, as shown by the neutralisation of the treatment effect after adjustment for change of heart rate at 28 days (HR 0·95, 0·85–1·06, p=0·352).
Our analysis confirms that high heart rate is a risk factor in heart failure. Selective lowering of heart rates with ivabradine improves cardiovascular outcomes. Heart rate is an important target for treatment of heart failure.