Atrial fibrillation (AF) is the most common cardiac arrhythmia and increases the risk of stroke and systemic embolism. The prevalence of AF increases with age and is more common in the male population. Oral anticoagulation therapy is the standard of care for outpatient prevention of stroke and systemic embolism.
The availability of the direct Xa inhibitors – apixaban, edoxaban and rivaroxaban – in clinical practice is leading a paradigm shift in anticoagulation for the management of venous thromboembolism (VTE) and stroke prophylaxis in the context of non-valvular atrial fibrillation. A common side effect experienced by patients receiving rivaroxaban in clinical trials was dizziness and headache, with a reported incidence of between one in 10 and one in 100 patients. Clinical experience has seen patients reporting rivaroxaban associated headaches and dizziness, leading to discontinuation of therapy. Given that widespread use of these agents is likely to be within an older adult population, it is important to understand the mechanism behind clinical observations which may then allow us to determine why some patients are affected more than others. Dr Jon Mabley and Dr Greg Scutt are working on a project led by collaborators from King’s College London (Dr Jig Patel and Professor Roopen Arya) which is investigating whether rivaroxaban causes direct vascular arteriodilation, resulting in headaches and dizziness requiring discontinuation of treatment.
Our preliminary data suggests that rivaroxaban may have a direct arteriodilatory effect which may provide a possible explanation for dizziness and headaches experienced by some rivaroxaban treated patients. The project is now investigating the precise mechanism behind the arteriodilatory properties of the drug, and whether the pharmacological activity extends to other direct Xa inhibitors.
This research project commenced in 2015 and is ongoing.
We aim to identify the mechanism through which rivaroxaban, and potentially other direct Xa inhibitors, cause arteriodilation.
Our preliminary data suggest that rivaroxaban has arteriodilatory properties. Further work is necessary, but this may have profound implications for clinical practice, especially for older patients, patients with cardiovascular disease, and patients receiving concomitant antihypertensive therapy.
Dr Jon MableyDr Greg Scutt
Mabley J, Scutt G, Lang K, Patel J, Arya R. (2015) Rivaroxaban-mediated vascular relaxation as a potential cause of headaches and dizziness. Oral abstract presentation. 57th Annual Meeting and Exposition, American Society of Haematology. Orlando, Florida, USA. 5–8 December.
Dr Jignesh Patel, Institute of Pharmaceutical Sciences, King’s College London
Professor Roopen Arya, King's Thrombosis Centre, Department of Haematological Medicine, King's College Hospital NHS Foundation Trust