New antithrombotic drugs: a revolution in stroke management

Embolism of cardiac origin accounts for 20% of ischaemic strokes. Atrial fibrillation is by far the most common cause of cardioembolic stroke, and anticoagulation is the treatment generally indicated for secondary, and in many cases, primary prevention. 1 The decision to prescribe warfarin is usually based on an accurate assessment of the likely absolute annual risk of stroke without warfarin, and whether or not such benefits of warfarin treatment are likely to outweigh the risk of bleeding associated with its use. For more than 20 years, the use of warfarin has been the cornerstone of antithrombotic therapy for patients with TIA or ischaemic stroke due to cardioembolism, particularly those associated with atrial fibrillation. Warfarin remains the commonest anticoagulant used worldwide (although other similar vitamin K antagonists are prescribed in many countries). Adjusted-dose warfarin anticoagulation with an international normalised ratio (INR) range between 2.0 and 3.0 is significantly more effective than antiplatelet therapy for preventing recurrent stroke in patients with atrial fibrillation and results in a risk reduction of between 60 and 68% compared to placebo. By contrast, the most commonly used alternative to warfarin is aspirin, which provides substantially less-consistent benefit and reduces the risk of recurrent stroke and other major vascular events in patients with atrial fibrillation by only 17 to 21%. Similarly, combination antiplatelet therapy with aspirin and clopidogrel is not as effective as warfarin and is associated with a significant increase in major bleeding. 6 Furthermore, although current data indicate that combination treatment with aspirin and clopidogrel does result in a greater reduction in major vascular events when compared with aspirin alone, this is offset by an increase in major haemorrhages. The absolute benefit of oral anticoagulation with warfarin versus antiplatelet therapy increases as patients with atrial fibrillation get older because stroke risk increases with age while the relative efficacy of oral anticoagula-tion therapy to prevent ischaemic stroke does not change. 7 Despite the efficacy and affordability of warfarin, many patients with cardioembolic stroke or TIA are not treated with this agent because it is perceived to be inconvenient or hazardous. Although the benefits of oral anticoagulation with warfarin are supported by a high degree of evidence for stroke prevention due to cardioembolic stroke, there are many disadvantages associated with its use. The long-term efficacy and safety of warfarin depends on maintaining a narrow range of anticoagula-tion intensity (INR 2.0–3.0) and this may be compromised by the …