What is the role of anticoagulation in symptomatic stenoses of extracranial and intracranial arteries due to stroke?

Updated: Dec 18, 2018
  • Author: Salvador Cruz-Flores, MD, MPH, FAHA, FCCM, FAAN, FACP, FANA; Chief Editor: Helmi L Lutsep, MD  more...
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Answer

Answer

No current evidence-based guidelines address anticoagulation in these patients. Oral anticoagulation (target INR 3-4.5) was compared with aspirin (30 mg/d) in patients with transient ischemic attack (TIA) or minor ischemic stroke of presumed arterial origin in the Stroke Prevention in Reversible Ischemia Trial (SPIRIT), but the trial was stopped after the first interim analysis because of increased major bleeding complications in the anticoagulant group. [44]

The Warfarin-Antiplatelet Recurrent Stroke Study (WARSS) compared oral anticoagulation (target INR 1.4-2.8) with ASS (325 mg/d) and failed to show any superiority of warfarin over aspirin; in fact, trends toward aspirin's superior efficacy were seen in all but the "cryptogenic" stroke group. [45]

The European/Australian Stroke Prevention in Reversible Ischaemia Trial (ESPRIT) assessed whether oral anticoagulation with an INR target range of 2-3 is superior to aspirin in treating patients after nondisabling cerebral ischemia of arterial origin, [46] but this trial was ended prematurely because ESPRIT had previously reported that the combination of aspirin and dipyridamole was more effective than aspirin alone.

Mean follow-up in ESPRIT was 4.6 years, and the mean achieved INR in the patients on anticoagulants was 2.57. While no difference was reported in the primary end point (composite of death from all vascular causes, nonfatal stroke, nonfatal myocardial infarction, or major bleeding complication, whichever occurred first), the rate of major bleeding complications was significantly higher in the anticoagulation group.

As a conclusion from ESPRIT, oral anticoagulants (target INR 2.5, range 2-3) are not more effective than aspirin (or aspirin in combination with dipyridamole) for secondary prevention after TIA or minor stroke of arterial origin.

The Warfarin-Aspirin Symptomatic Intracranial Disease (WASID) trial compared the efficacy of warfarin with an INR target range of 2-3 and aspirin (1300 mg/d) in patients with symptomatic stenosis (50-99%) of a major intracranial artery, [4] but after 569 patients had been randomized, enrollment was stopped because of concerns about the safety of the patients who had been assigned to receive warfarin.

Whereas there was no difference in the primary end point (ischemic stroke, brain hemorrhage, or death from vascular causes other than stroke) between the warfarin group and the aspirin group, warfarin was associated with significantly higher rates of adverse events (death, major hemorrhage, and MI or sudden death). [4]

As a consequence of WASID, warfarin cannot be recommended for first-line use in patients with intracranial arterial stenosis. Aspirin (or other antithrombotic drugs) should be preferred. [4]

A systematic review of controlled studies found no evidence of benefit from prolonged anticoagulation therapy in patients who have experienced presumed non-cardioembolic ischemic stroke or TIA; rather, anticoagulation increased the risk of fatal intracranial hemorrhage and of major extracranial hemorrhage. [47] The reviewers noted that the study rates were equivalent to anticoagulation causing about 11 additional fatal intracranial hemorrhages and 25 additional major extracranial hemorrhages per year for every 1000 patients treated.

A few retrospective studies suggest that anticoagulation might be effective in patients with basilar artery dolichoectasia.


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