Thoughts on the WASID trial

The warfarin-Aspirin Symptomatic Intracranial Disease (WASID) trial compared aspirin with warfarin and found no benefit from warfarin, but greater safety risks, leading the authors to conclude that there was no justification to use warfarin in this situation.

An editorial by Walter Koroshetz accompanying the landmark study (NEJM 2005;352:13)provides acceptance of the studies with enough included analysis of the detail to make a reasoned opinion about its limitations. Ischemic stroke, brain hemorrhage, or death from vascular causes other than stroke occurred in 22 % of patients in either group. Recurrent stroke did not differ in the two groups (.2 in ASA, .17 in warfarin groups). In WASID, 73 % of recurrent stroke occurred in the index vessel.

Problems: 1) ASA dose of 1250 per day is nonstandard 2) the target INR of 2-3 was reached only about 63 % of the time and 3) 28 % of patients dropped out of the warfarin group. The rate of stroke related to IN mattered. It was 25 per 100 patient years with a subtherapeutic INR, 5.0 per 100 patient years with a therapeutic INR. Koroshetz notes that the "data suggest that anticoagulation within the therapeutic range is associated with a striking reduction in the risk of cerebrovacular and cadiovascular events." The problem, is achieving anticoagulation within the therapeutic range, either in a trial or in clinical practice. Koroshetz further notes that "the WASID data do not necessarily suggest that all patients with symptomatic intracranial stenosis should be treated with aspirin during all phases of their disease and be left to face a 22 % two year risk of ischemic stroke, brain hemorrhage or death from vascular causes other than stroke that the WASID trials predicts." There is a very high risk period right after enrollment, due to recurrent stroke, and Koroshetz suggests using Lovenox followed by anticoagulation rather than just warfarin.

Blogger comment: Recall that in most clinical trials of ASA (not for intracranial stenosis) the NTT for saving one person from a stroke is very high,, ranging from 79 to 129 in various aspirin trials, with the NTT for Plavix around 50 and for Aggrenox around 37. So for a disease with a 1/5 risk of stroke, aspirin may be better/safer than warfarin but still is not that good. So, a treatment, any treatment, that can improve those odds in a high risk group is desperately needed. If a new drug came forth that anticoagulated and could be kept in range reliably (unlike warfarin , which WASID proved can't be) another clinical trial for intrancranial stenosis would be indicated.

One last note-- it shold be noted that some of the initiators of the WASID and WARRS trials are Bostonians who have historically been dedicated warfarin users. These neurologists deserve our credit for designing and properly critiquing the studies here.