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Atrial fibrillation (AF) is the commonest sustained cardiac arrhythmia, whose importance has been realised given its strong association with stroke and systemic embolism that can be significantly reduced by oral anticoagulation. Until recently, the only oral anticoagulant (OAC) available was the vitamin K antagonist (VKA) class of drugs—for example, warfarin. Indeed, warfarin provides highly effective prophylaxis against thromboembolism as shown by extensive evidence from randomised controlled trials, but its effectiveness is dependent upon good anticoagulation control (as reflected by its high length of time in the therapeutic range).1
The risk of stroke in AF is not homogeneous, and depends upon the presence or absence of several risk factors. These risk factors have been used to formulate stroke risk stratification schemes, so that the focus has been to identify ‘high-risk’ patients who could be targeted for this ‘inconvenient’ drug, warfarin.
The numerous practical limitations which affect a clinician's willingness to prescribe warfarin, and a patient's willingness to comply with it (box 1), have resulted in large numbers of high-risk patients either unprotected against stroke or suboptimally protected with antiplatelet therapy2—despite evidence that aspirin is less effective for stroke prevention and is not without its own bleeding risk, especially in the elderly.3
Limitations of warfarin
Frequent monitoring necessitating regular clinic attendance
Unpredictable pharmacodynamics and pharmacokinetics
Inter- and intraindividual dose variability
Narrow therapeutic window
Slow onset and offset of action
Drug and dietary interactions
Genetic polymorphishms exist which confer increased sensitivity or resistance to warfarin
The limitations of warfarin have driven efforts to establish new OACs which can circumvent the shortcomings of the VKAs. The new OACs fall into two classes: the oral direct thrombin inhibitors (eg, dabigatran) and the oral factor Xa inhibitors (eg. rivaroxaban, apixaban).4
The National Institute for Health …
Competing interests GL has served as a consultant for Bayer, Astellas, Merck, AstraZeneca, Sanofi, BMS/Pfizer, Daiichi-Sankyo, Biotronik, Portola and Boehringer Ingelheim and has been on the speakers bureau for Bayer, BMS/Pfizer, Boehringer Ingelheim, and Sanofi Aventis. YA: none declared.
Provenance and peer review Commissioned; internally peer reviewed.