Future anticoagulation therapy for AF

After much deliberation, the National Institute for Health and Clinical Excellence (NICE), the body responsible for developing national guidance on safe and cost-effective treatments, gave the final approval earlier this year for the use of dabigatran etexilate (also commonly known as pradaxa and rivaroxaban) in the prevention of stroke and systemic embolism in patients with atrial fibrillation (AF). AF is a condition whereby the heart’s chambers fail to beat in rhythm, causing blood to pool and to potentially form clots. These clots can be dislodged, but then may block small blood vessels in the brain, eventually causing a stroke. AF now affects approximately 1.2 million UK patients and causes one in seven first time strokes, equivalent to 12,500 episodes a year. Previously, patients with AF were limited to using oral anticoagulant warfarin therapy. There are currently an estimated 750,000 patients in the UK now receiving this treatment, but this number is forecast to rise even further over the next decade. The requirement for anticoagulation monitoring has been steadily climbing since clinical trials demonstrated that treatment using warfarin significantly reduces the risk of strokes in patients suffering from atrial fibrillation. For anticoagulation prophylaxis programmes to be successful, the regular monitoring of the patient’s international normalised ratio (INR) is necessary to ensure that the INR remains within a specified therapeutic range to avoid potential bleeding and avoidance of further strokes. Unlike warfarin, however, dabigatran does not require frequent blood testing and constant INR monitoring. Therefore, when prescribed in the recommended daily dose of 300 mg, taken as one 150 mg capsule twice daily, dabigatran represents a useful alternative option for AF patients. Despite the recent NICE approval, dabigatran is not without its own issues, however.

NICE recommendations

When the NICE technical appraisal and guidance on the use of dabigatran was released in March 2012, it came with several specific provisos. Firstly, it was only recommended as an option for the prevention of stroke and systemic embolism within its licensed indication – that is, in people with nonvalvular atrial fibrillation with one or more of certain risk factors. These were in patients who had suffered previous stroke, transient ischaemic attack or systemic embolism, those with a reduced left ventricular ejection fraction, an elevated symptomatic heart failure, patients aged 75 years or older and, finally, in patients aged 65 years or older also diagnosed with diabetes mellitus, coronary artery disease or hypertension. NICE stated that dabigatran, given 150 mg twice daily, was more clinically effective than warfarin in reducing the risk of stroke or systemic embolism, ischaemic stroke and vascular mortality – whereas dabigatran 110 mg twice daily was non-inferior to warfarin. Although NICE concluded that dabigatran represented an important development for people with atrial fibrillation, it also went on to state that the actual decision about whether to start treatment with dabigatran should only be made after an informed discussion has taken place between the clinician and patient about the risks and benefits of dabigatran compared with warfarin. Furthermore, for people who are taking warfarin, the potential risks and benefits of switching to dabigatran should be considered in light of their level of INR control.