The introduction of factor Xa inhibitors has offered an alternative to the vitamin K antagonist, warfarin, for primary risk reduction of strokes in patients with atrial fibrillation. In one study by Granger and coworkers that used apixaban for this purpose, there were slightly fewer strokes and fewer cerebral hemorrhages than with warfarin when the intended goal with warfarin was to keep the INR between 2 and 3. Dabigatran and rivaroxaban confer similar reductions in stroke to apixaban and warfarin in atrial fibrillation (c.f., Patel et al). These drugs have the advantage over warfarin of not requiring regular blood tests for the measurement of the INR and of having fewer drug interactions. However, although they have short half-lives compared to warfarin, they are still present for many hours after discontinuation and anticoagulation is not easily reversible should there be systemic or cerebral bleeding. Drugs that reverse the anticoagulant effect of these new drugs are available or being developed. (We mention here that reversal the effect of warfarin with, for example, vitamin K, and even with clotting factors, is also not rapid).
A frequent clinical problem arises in an elderly patient with atrial fibrillation who is at risk of falling from any of a number of causes including the stroke itself. In a review of selected administrative database records, Gage and colleagues concluded that the overall risk of inducing cerebral hemorrhage in older patients with atrial fibrillation treated with warfarin was lower than the risk of recurrent stroke. In those patients who had hemorrhages while receiving warfarin, they were, however, more likely to be fatal. Of course, decisions about anticoagulation must be tailored to the conditions of the individual patient.
For patients with atrial fibrillation of recent onset, an attempt should be made to restore normal sinus rhythm by the use of electrical cardioversion or a trial of antiarrhythmic drugs. If these fail, prophylactic anticoagulant therapy is recommended. Before attempting cardioversion of more long-standing atrial fibrillation, anticoagulation for several days or longer is advisable to reduce emboli.
Anticoagulant therapy may also be desirable for at least several weeks in patients with acute myocardial infarction, especially if the left side of the heart is involved. No guidelines have been established in these circumstances; the new common use of one or more platelet aggregation inhibitor drugs after myocardial infarction may preclude the concurrent use of warfarin. In cerebral embolism associated with bacterial endocarditis, anticoagulant therapy should be used cautiously because of the danger of intracranial bleeding, and one proceeds instead with antibiotics. Generally, we have not anticoagulated these patients.
Aspirin has proved to be the most consistently useful drug in the prevention of thrombotic and possibly, embolic strokes but its effects have been small in large trials both for primary prevention and for reducing the risk of a recurrent stroke. The acetyl moiety of aspirin combines with the platelet membrane and inhibits platelet cyclooxygenase, thus preventing the production of thromboxane A2, a vasoconstricting prostaglandin, and also prostacyclin, a vasodilating prostaglandin. One currently favored approach, based in part on the WARSS trial, is to simply administer aspirin in all cases of acute stroke. This approach is further endorsed by the WASID trial comparing aspirin (1,300 mg/d) to warfarin for treatment of intracranial arterial stenosis on the basis that warfarin was no better at preventing strokes while aspirin was associated with fewer gastrointestinal hemorrhages and a lower overall death rate. Confirmation of this approach was given by the IST and CAST trials that established a modest reduction in mortality and stroke recurrence if aspirin was given within 48 h of stroke. Whether low doses of aspirin (50 to 100 mg) or high doses (1,000 to 1,500 mg) provide equivalent protection is still uncertain.