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dabigatran

Atrial fibrillation-potential of new treatments

Ami Banerjee
Last edited 21st April 2011

Everybody seems to be interested in atrial fibrillation (AF) at the European Stroke Conference this week in Barcelona. So they should be as AF is the most common heart rhythm problem, affecting up to 1% of the population, and increasing with age. Usually an electrical impulse passes from the upper chambers of the heart (the atria) to the lower chambers (the ventricles), which pump blood around the body. If the electric impulse is not conducted properly, the atria “fibrillate” or “flutter” instead of beating in the usual coordinated way. When this happens, clots tend to form in the heart. AF increases risk of stroke by 5-fold due to these clots being thrown off into the brain. Strokes due to AF tend to be more severe and disabling than other types of strokes, with 25% mortality rate. But we have known about AF and the need to prevent strokes by thinning the blood with warfarin for many years, so why all the sudden interest?

We know that warfarin is better than aspirin and clopidogrel and aspirin alone in preventing strokes in people with AF from existing trial data. Therefore, warfarin is recommended in people with moderate or high risk of stroke. The problem is that people on warfarin need their blood monitoring and there is a risk of bleeding, as well as lots of interactions with other drugs and food. In people who cannot take warfarin, aspirin is better than nothing. I have previously mentioned the evidence that self-monitoring of INR levels in patients taking warfarin leads to better results. However, there has been a search for new drugs which avoid blood monitoring and are easier to take.

Dabigatran is such a drug. The RE-LY trial compared dabigatran to warfarin in stroke prevention in patients with AF other risk factors for stroke,such as age or heart failure. The relative risk of stroke with digabatran was two-thirds that of warfarin (remind yourself of what relative risk is). Importantly the new drug caused much less bleeding and you don’t have to worry which other drugs you are taking or what you are eating. There are lots of other drugs being trialled at the same time, but dabigatran is probably the most promising and has got the best results in the trials.

Another way to treat the problem is to treat the AF directly and try and make the heart rhythm return to normal. This has traditionally been done with drugs (known as anti-arrhythmics such as amiodarone), but surgical therapies have become available over the last 20 years. Over the last 10-15 years, cardiologists have been increasingly using techniques to burn the electrical pathways that are at fault in the atria. The procedure is currently recommended in patients who do not respond to drugs and still have symptoms from their AF such as palpitations. There are trials ongoing to test this long procedure, but one of the presenters (a cardiologist who was a proponent of the technique from France) raised the issue that it is difficult to envisage a time when the procedure will be available to large enough section of the population with AF. In other words, it requires so much time and expertise that providing enough training resources, human resources and enough hospital resources may be challenging. But would we want to offer everybody this procedure anyway? There must be cheaper, more effective alternatives.

Stroke and AF are totally intertwined and both are growing problems in ageing populations across the world. That is why researchers and drug companies are so interested because the potential rewards are huge.

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