Acv Ischaemic Stroke

REVIEWS
Anticoagulant therapy for patients with ischaemic stroke
Graeme J. Hankey
Abstract | Anticoagulant therapy for ischaemic stroke aims to prevent recurrent ischaemic stroke and venous thromboembolism. Several large clinical trials have provided insight into the safety and efficacy of anticoagulant therapies. Anticoagulant treatment provides no net benefit over placebo or antiplatelettherapy in patients with acute ischaemic stroke of arterial or cardiac origin, because reductions in early recurrent ischaemic events and venous thromboembolism are offset by increases in bleeding events. For patients with ischaemic stroke of cardiac origin due to atrial fibrillation, long-term warfarin treatment reduces the risk of recurrent stroke by two-thirds compared with control, and by halfcompared with antiplatelet therapy. New anticoagulants, such as dabigatran, rivaroxaban and apixaban, are as efficacious and safe as warfarin, and have a rapid onset of action, few drug interactions, and predictable anticoagulant effects that do not require routine monitoring. However, the anticoagulant effects of the new drugs cannot be reliably measured or rapidly reversed in the event of majornon-compressible bleeding or urgent surgery. In addition, the new agents cannot be used in patients with severe renal impairment or active liver disease. Ongoing research aims to resolve these limitations, examine whether the promising results of clinical trials can be translated into clinical practice, and monitor the long-term safety of anticoagulant therapies.
Hankey, G. J. Nat. Rev. Neurol.advance online publication 8 May 2012; doi:10.1038/nrneurol.2012.77

Introduction
For patients with ischaemic stroke or transient ischae­ mic attack (TIA) caused by in situ arterial thrombosis or thromboembolism, anticoagulant therapy is used to prevent recurrent ischaemic stroke and venous thrombo­ embolism. For patients with ischaemic stroke or TIA and atrial fibrillation, anticoagulantintervention with oral vitamin K antagonists (VKAs), such as warfarin, has been the mainstay of treatment to prevent recurrent stroke. Long­term warfarin treatment is highly effective when given at an optimal dose maintaining the international normalized ratio (INR) within the therapeutic range (INR 2–3). However, this drug is substantially under­ used owing to concerns over the risk of bleedingand, when it is used, the dose is generally lower or higher than is required to maintain the INR within the therapeutic range, mainly because of pharmacological limitations, such as interactions with food and other drugs that alter the metabolism of warfarin (Table 1).1–7 Suboptimal use of warfarin has serious consequences: for every 10% reduction in time in the therapeutic range (TTR) of the INR,the absolute annual risk of stroke is increased by 1%.6 Furthermore, the severity of strokes caused by atrial fibrillation, which could have been pre­ vented by appropriate and optimal use (INR 2–3) of
Competing interests G. J. Hankey declares associations with the following companies: Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Johnson & Johnson, Pfizer, Sanofi-Aventis. See the articleonline for full details of the relationships.

anticoagulant treatment, is particularly high. One study showed that at 3–6 months’ follow­up, 73% of patients with ischaemic stroke caused by atrial fibrillation had died or were dependent on others to perform daily activities.8 The underuse and suboptimal use of warfarin in patients with atrial fibrillation and at risk of stroke has prompted thedevelopment and evaluation of three new oral anti­ coagulants for stroke prevention: the direct thrombin inhibitor dabigatran, and the activated factor X inhibi­ tors rivaroxaban and apixaban (Figure 1).9,10 This article provides an updated review of the evidence for the safety and efficacy of anticoagulant therapies in prevention of recurrent ischaemic stroke caused by arterial and cardiac...