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ivabradine

Slow and steady wins the race when it comes to heart failure

Ami Banerjee
Last edited 30th August 2010

Heart failure is a major cause of death all over the world, but also causes a lot of disability as a chronic condition, especially with ageing populations. 2-3% of the population suffer with heart failure. Heart failure patients are often prescribed a whole range of medicines to treat their blood pressure, kidney disease and many other conditions. One more tablet called IVABRADINE (or Procoralan) looks set to join the list. I just saw the results of the SHIFT trial presented at the European Congress of Cardiology in Stockholm today and they were simultaneously published in the Lancet online.

50% of heart failure patients have a high heart rate (defined as greater than 70 beats per minute). Beta-blockers reduce the heart rate and have been shown to reduce mortality in heart failure. However, they are not always tolerated well, partly because they also cause a drop in blood pressure. Ivabradine is a new drug which reduced heart rate without much effect on blood pressure, and so may be a new option to treat heart failure.

The SHIFT trial was a double-blinded, placebo-controlled, randomised controlled trial of ivabradine in 6500 patients with moderate to severe heart failure and a regular heart rhythm. This trial specifically looked at the heart rate of patients at the start of the trial (“baseline”) and throughout the trial. The main or primary outcome of the trial was death or hospitalisation due to heart failure. Double blinding means that neither the patients nor the researchers knew which treatment the patients received. Controlling with a placebo allows the researchers to estimate the effect of the drug beyond no treatment. Randomisation means that patients randomly received placebo or the drug (in this case, ivabradine), and removed bias in the selection of patients. The trial lasted for just under 2 years.

Basically, ivabradine reduced death and hospitalisations by 18%, and the drug was very well tolerated, with few side effects of unduly low heart rate (bradycardia) or low blood pressure. The authors concluded that for every 1 beat per minute increase in heart rate, there was a 3% increase in mortality in a continuous relationship. They also found that baseline heart rate predicted the degree of risk of death, and interestingly, patients with the highest heart rate at baseline had the greatest reduction in heart rate with the drug, ivabradine. High heart rate has been shown to be a “risk marker” for outcome of patients with heart failure. This trial seems to suggest that a high heart rate may also be a “risk factor” for heart failure, i.e. it may have a role in causing the disease. Either way, “the slower, the better” seems to be the motto for the heart when it is failing.

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