CASE IN POINT -COMPARISON OF WARFARIN AND ASPIRIN FOR INTRACRANIAL STENOSIS (THE WASID TRIAL)
The March 31 issue of NEJM published the WASID trial.In summary, warfarin was not superior to high dose asa ( meaning 4 of the 325 mg tablets a day).Because there was more hemorrhage and no fewer ischemic strokes in the warfarin group the authors conclude "aspirin should be used in preference to warfarin in patients with intracranial stenosis"
We all eagerly await a reason not to give warfarin, so is the issue settled ? It may be that warfarin would be better if we could control the INR better but with current practices even in a RCT we apparently cannot.
The editorialist, Dr. W.J.Koroshetz makes interesting comments.The warfarin patients were in "therapeutic target " range of an INR of 2-3 only 63% of the time, which we are told is pretty good for trials of warfarin and probably higher than that achieved typically in real life outside of trials.For those with a less than 2 INR the rate of ischemic stroke was 25 per 100 patient years versus 5 per 100 patient years if IRN was in the 2-3 range. It seems that warfarin "works" to decrease ischemic stroke if it is done right but it hard to get it right. So,if INRs could be kept at 2-3, perhaps warfarin would be judged to be superior to asprin in ischemic stoke reduction with less of the hemorrhage concern.There is some data to indicate that home monitoring of INRs may be better and with Ximelagatran, which is in the wings, no monitoring is needed.
Dr. Koroshetz states that the WASID data does not necessarily mean not to use warfarin or some anticoagulant at all. He suggests possibly LMWH early on and still suggests a role for warfarin in those patients with have more clinical ischemic events while on aspirin.
There is also the issue of Aggrenox- the extended release dipyridamole-aspirin combination which was shown to be better than aspirin alone in the European stroke trial.In the ESPS2 trial the 2 year stroke risk in the placebo group was 15%,12.5 % for aspirin and 9.5% for the aspirin-dipyridamole capsule.
Also consider the issue of how much stroke risk reduction will occur in similar patients when their LDL is lowered (to less than 70??), and their BP is well controlled. Hopefully it will be lower than the 22 % 2 year risk reported in the aspirin group.