Family doctor

Dabigatran is a relatively new oral anticoagulant (blood thinner) that can be for stroke prevention in patients with atrial fibrillation (a condition in the heart beats irregularly, increasing the chance of clots forming in the body). Dabigatran is an alternative to the anticoagulant warfarin.

Doctors are increasingly becoming familiar with dabigatran and have been switching some patients, previously on warfarin, onto dabigatran as well as starting some patients straight onto dabigatran.

Why is it useful having an alternative to warfarin available?

Warfarin has been used for many years but has some limitations. Firstly it can be difficult to get patients into their 'goal range' where their blood is thinned to just the right degree and secondly it can be difficult to predict exactly what dose each person will need. In addition warfarin often needs dose adjustments over time due to interactions with certain foods and medicines - this ends up meaning that patients need to get frequent blood tests for monitoring purposes. Even if a patient is relatively stable on warfarin they still require blood testing every 4-6 weeks at least.

What advantages might there be in using dabigatran rather than warfarin?

In contrast to warfarin, dabigatran has a much more predictable effect on anticoagulation and therefore routine blood testing for monitoring is unnecessary (however if you are prescribed dabigatran your GP will want to check your kidney function in a yearly basis at least). In addition dabigatran appears to be at least as effective as warfarin for stroke prevention in patients with atrial fibrillation.

Which people may benefit from starting dabigatran?

Your GP may decide to prescribe you dabigatran if you have non-valvular atrial fibrillation and are in one of these catergories:

• You require anticoagulation and currently on no treatment
• You are already on warfarin but have some difficulties with monitoring, or dislike the frequent blood tests, or your blood tests show that you are often not in your goal range.

Which people may not particularly benefit from starting dabigatran?

Your GP may decide not to use dabigatran if you:

• Are on warfarin and on stable doses and do not mind about the need for frequent blood monitoring
• Would find it difficult to manage the twice daily dosing required for dabigatran
• Prefer to continue with warfarin (some patients may like the reassurance of periodic monitoring)

Who should definitely NOT be prescribed dabigatran?

Your GP will not prescribe you dabigatran if you:

• Have very poor kidney function (i.e. a creatinine clearance of less than 30 mL/min)
• Have had a recent haemorrhagic stroke (within the previous six months)
• Take oral ketoconazole
• Are bleeding or have a bleeding disorder
• Significant valvular heart disease or a mechanical heart valve (there is currently no evidence that dabigatran is suitable in these conditions)
• Have severe liver disease

What are the potential problems with dabigatran?

Like warfarin, dabigatran has the potential to cause bleeding as its most serious side effect. A trial (known as the RE-LY trial) showed that dabigatran (whether the 150 mg or 110 mg dose was prescribed), caused fewer intracranial haemorrhages and life-threatening bleeds compared to warfarin. However, major gastrointestinal bleeding rates were higher for patients on dabigatran than those on warfarin. See the end of this article for detailed statistics about the comparison of dabigatran versus warfarin.

If a serious bleed (e.g. bleeding from the gut) should occur while someone is taking dabigatran then there is no antidote for bleeding from dabigatran, unlike vitamin K for warfarin. If bleeding complications do occur then dabigatran treatment must be stopped.

Approximately one in ten patients who try dabigatran will experience 'stomach upset', so for this reason dabigatran may not be well tolerated particularly in people with gastrointestinal problems.

Like warfarin, there are some medicines for which your doctor will require a degree of caution when co-prescribing with dabigatran. These medicines are amiodarone, verapamil, rifampacin, and clarithromycin.

Dabigatran requires twice daily dosing, ideally 12 hours apart (in contrast to warfarin that only requires once daily dosing) for it to work well at keeping the blood adequately thinned. Some people can find that they forget to take it twice daily and if this is the case then this medicine is unsuitable for them to use.

What to do if you miss a single dose of dabigatran:

If a single dose is missed then the missed dose can be taken when you remember as long as it is more than six hours until the next dose is due. If it is within six hours of the next scheduled dose, then you should not to take the missed dose. A double dose should not be taken to make up for a missed dose.

Further reading;

RE-LY study results (the statistics)

The RE-LY trial randomised 18,113 patients to receive dabigatran 110 or 150 mg twice a day or warfarin dose adjusted to an international normalised ratio of 2.0 to 3.0 for a median follow-up of 2.0 years. The trial was particularly interested in recording the number of strokes or systemic embolisms that occurred in patients taking these medicines as well as any bleeding problems that occurred.

What was found was that dabigatran given at a dose of 110 mg was associated with rates of stroke and systemic embolism that were similar to those associated with warfarin dabigatran administered at a dose of 150 mg, as compared with warfarin, was associated with lower rates of stroke and systemic embolism: Stroke and systemic embolism rates were 1.69% per year in the warfarin group, as compared with 1.53% per year in the group that received 110 mg of dabigatran and 1.11% per year in the group that received 150 mg of dabigatran.

Both doses of dabigatran were associated with fewer intracranial haemorrhages and other life-threatening bleeds when compared to warfarin, however, gastrointestinal bleeding events were significantly increased with the higher dose of dabigatran: the rate of major bleeding was 3.36% per year in the warfarin group, as compared with 2.71% per year in the group receiving 110 mg of dabigatran and 3.11% per year in the group receiving 150 mg of dabigatran. The rate of haemorrhagic stroke was 0.38% per year in the warfarin group, as compared with 0.12% per year with 110 mg of dabigatran and 0.10% per year with 150 mg of dabigatran.

Despite the rate of myocardial infarction (heart attack) being higher in patients in the dabigatran group there were no significant differences in the mortality rates from any cause between either of the dabigatran treatment groups and the warfarin group: the mortality rate was 4.13% per year in the warfarin group, as compared with 3.75% per year with 110 mg of dabigatran and 3.64% per year with 150 mg of dabigatran.

In summary, patients with atrial fibrillation, dabigatran given at a dose of 110 mg was associated with rates of stroke and systemic embolism that were similar to those associated with warfarin, as well as lower rates of major haemorrhage. Dabigatran administered at a dose of 150 mg, as compared with warfarin, was associated with lower rates of stroke and systemic embolism but similar rates of major haemorrhage.

Reference:

Connolly S, Ezekowitz M, Yusuf S et al. Dabigatran versus Warfarin in Patients with Atrial Fibrillation. N Engl J Med 2009; 361(12):1139-51