When there is a compelling reason after an embolic stroke in a non-fibrillator to anticoagulate a patient for secondary stroke prevention (e.g., mechanical heart valve, known left ventricular thrombus, hypercoagulable state, and perhaps patent foramen ovale with deep venous thrombosis), opinions vary about the use and precise timing of instituting an anticoagulant. In a patient with atrial fibrillation who has had a recent embolic stroke, the concern for risk of hemorrhagic transformation of the ischemic area has led to the practice of a delay of up to several weeks in starting treatment. Many practitioners will start anticoagulation in the acute phase under these circumstances if the stroke is small. Details pertaining to anticoagulation in atrial fibrillation can be found earlier under “Anticoagulants for the Primary Prevention of Strokes from Atrial Fibrillation.”
While anticoagulation is established as a treatment for primary and secondary prevention of embolic strokes with atrial fibrillation, the situation with other strokes, including those presumed to be embolic strokes, is not clear (called “embolic stroke of uncertain source”). For example, a trial conducted by Hart and colleagues (2018) showed that rivaroxaban was not more effective than aspirin for the prevention of a second stroke after a stroke that was presumed to be embolic, but not due to atrial fibrillation or extracranial vascular disease.
For warfarin, in the past, there had been a concern for the theoretical risk of transient hypercoagulability when starting the drug (due to upregulation of protein S); this, and a desire to institute anticoagulation rapidly, led to a strategy of “bridging” with heparin or a low-molecular-weight heparin while awaiting the effects of warfarin to be evident. This risk has seemingly not had clinical significance. On the basis of the aforementioned trials of acute anticoagulation that showed only a 1 to 2 percent frequency of early recurrent stroke, most clinicians have eschewed the “bridging” approach. The view that opposes heparin or a similar bridging anticoagulant is based also on a retrospective study by Hallevi and colleagues, supported by a meta-analysis reported by Whiteley and coworkers, that found higher rates of symptomatic and serious bleeding in the brain or systemically with the bridging strategy.
A common problem in general medicine is that of the need to discontinue warfarin in patients with atrial fibrillation who must undergo an invasive diagnostic procedure or surgery. Little guidance can be offered except that a randomized trial conducted by Douketis and colleagues suggested that foregoing interim anticoagulation with low-molecular weight heparin was non-inferior to foregoing this bridging treatment.
Anticoagulation for prevention of recurrent stroke with atherosclerotic disease There had been a notion that warfarin is of some value in the first 2 to 4 months following the onset of an ischemic stroke due to atherosclerotic disease. However, the results of controlled studies have indicated that there is no reason to favor warfarin in comparison to aspirin in cases of atherothrombotic stroke. This was amply shown in the Warfarin-Aspirin Recurrent Stroke Study (WARSS; not including cardioembolic stroke) reported by Mohr and colleagues (2001); over 2 years the recurrent stroke rate was about 16 percent in both groups, and, surprisingly, the rate of cerebral hemorrhage was similar (near 2 percent). Similarly, for the special case of TIA or stroke that is shown to be because of intracranial atherosclerosis, Chimowitz and colleagues in the Warfarin-Aspirin Symptomatic Intracranial Disease (WASID) trial have suggested that warfarin provided no benefit over aspirin in preventing subsequent cerebrovascular events but warfarin had more risk as commented below. The WASID trial exposed not so much the deficiency of warfarin in prevention of stroke as much as the difficulties in its use, as pointed out by Koroshetz.