Anticoagulants prevent stroke in atrial fibrillation patients

29 January 2018

Atrial fibrillation (AF) is a type of irregular heart beat and is a major cause of blood clots and stroke.

Medicines called warfarin and direct-acting oral anticoagulants (DOACs) can both be used to prevent blood clots and strokes in people with AF. Now, a major new study has shown that DOACs are better at preventing stroke, safer and more cost effective.

In an important review published in the BMJ (British Medical Journal) in December, researchers looked at all the published research comparing different DOACs with each other and with warfarin in patients with AF. Almost 100,000 people in 23 studies were included in the research, which found DOACs to be preferable overall.

DOACs were found to be safer, more effective than warfarin

The researchers found that DOACs were more effective at reducing the risk of stroke, blood clots and death from any cause. Importantly, they were also safer to use. As DOACs and warfarin thin the blood to prevent blood clots, they carry a risk of bleeding. DOACs had a lower risk of major bleeding and bleeding in and around the brain than warfarin, however there was a higher risk of gastrointestinal bleeding with DOACs.

Comparing the DOACs  

There are a number of DOACs available and this study found that they vary in how well they work at preventing different problems. The DOACs apixaban, dabigatran, edoxaban and rivaroxaban all showed benefit over warfarin. Apixaban was the most effective overall – it was best at preventing stroke, blood clots, heart attacks and death from any cause, and was also the safest with the lowest risk of bleeding.

The DOACs varied in their cost-effectiveness, taking into account savings on future healthcare costs, but all were more cost effective than warfarin. Even though Apixaban was the most expensive, it was the most cost effective because it has the most benefit.

Why was this study needed?

Atrial fibrillation is a common problem which becomes more common with age, affecting roughly 9% (nine in 100) of 80 – 90yr olds. It raises the risk of a stroke caused by a blood clot (ischemic stroke) by five times, and causes a fifth of strokes in England and Wales. Not only does AF make strokes more likely, strokes caused by AF can lead to more complications than other types of stroke.

Warfarin is effective at preventing stroke in patients with AF, but comes with a number of limitations. It can cause bleeding, it’s slow to start working, it can interact with other medicines and some foods, and needs careful monitoring. Because of these limitations, it’s not always used when needed or is not used to an adequate dose, meaning people live without treatment, facing the risk of stroke.

DOACs overcome some of these barriers. They don’t need monitoring, it’s easier to treat people with an adequate dose and they have fewer interactions with other drugs. However, they are more expensive than warfarin, and it wasn’t clear whether the benefits of lower monitoring and future healthcare costs would off-set the higher cost of the drug.

There was also no clear evidence comparing DOACs, making it difficult to recommend one over another.

What this study adds

DOACs are already used to treat AF, and before now research has suggested that DOACs work at least as well as warfarin, are safer and may overcome some of the limitations or warfarin. The National Institute for Health and Care Excellence (NICE) have also recommended their use. 

This study confirms these findings and adds depth to our knowledge, and for the first time shows that DOACs are more cost effective than warfarin, despite the higher cost of the drug. Taken together, these make DOACs preferable to warfarin. The authors note that while DOACS are more expensive, the cost could be reduced in future as generic DOACs become available.

This is also the first study to compare the different DOACs, finding the apixaban could be the most effective overall.

Next steps

Although this study indicates that apixaban is the most effective, a trial designed to compare DOACs directly would be the best way to compare their safety and how well they work. This would provide clear guidance on which DOACs to use, especially when apixaban isn’t suitable due to other health problems or medications.

There is also a need to develop treatments for reversing the anticoagulant effects of DOACs if needed.

Nirmala Markandu, Hypertension Nurse Specialist at Blood Pressure UK explains:  

“High blood pressure and atrial fibrillation are both major causes of stroke, and many people have both together –38% of the patients in this study had had high blood pressure. Over the last year we have focused our campaigning on preventing stroke, and any developments in putting an end to strokes is incredibly welcome. 

"DOACs are already widely-used treatment for atrial fibrillation and this study recommends their use as a first line treatment for AF ahead of warfarin.  We hope for further guidance from NICE in light of this study which will lead to their widespread and cost-effective use.”

Read more

Read the review in full in the BMJ