The Middle East Dual Anti-platelet Treatment in Acute Transient Ischemic Attack.10 vs 30 Days of Combination ASA and Clopidogrel Study

Transient Ischemic Attacks (TIAs) are common, easily misdiagnosed, not investigated appropriately and are often harbingers of disabling strokes. A TIA is best defined as an episode of neurological dysfunction caused by focal ischemia that lasts for less than 24 hours (very often less than an hour). Minor stroke (NIHSS of <3) is often lumped together with TIAs. The distinction between minor ischemic stroke and TIA is unimportant in terms of prognosis. Numerous studies have shown that short-term risk of stroke is high after TIA and minor ischemic stroke, particularly in the first few days, even in patients treated with aspirin, the current standard of care. In patients with TIAs and minor stroke effective therapies can significantly reduce the overall burden of stroke if initiated immediately. The recently completed CHANCE study comprising more than 5000 patients with TIAs and minor stroke showed that a short course of combination antiplatelet medications (ASA+clopidogrel) for 3 weeks significantly reduced the 90-day risk of stroke when compared to ASA treatment.

There are three trials where patients with TIAs and minor strokes were treated early after onset of symptoms with combination treatment with clopidogrel and ASA versus ASA alone. FASTER was a pilot trial based in Canada (5). It evaluated clopidogrel (300 mg load and 75 mg/day afterwards) on a background of aspirin in patients presenting within 24 hours of a TIA or minor stroke. The trial enrolled 392 patients. The risk of stroke (ischemic or hemorrhagic) at 90 days was 11% in those treated with aspirin alone and 7% in those treated with clopidogrel and aspirin, a non-significant 36% relative risk reduction (RRR) in this pilot trial (p=0.19). There were two Intra cerebral hemorrhages(ICHs) and these were both in patients treated with clopidogrel and ASA.

The recently completed CHANCE trial (5170 patients enrolled within 24 hours of symptom-onset) from China showed that in patients with high-risk TIAs and minor strokes, there was a significant absolute reduction of early stroke at 90 days from 11.7 % to 8.2 % hazard ration (HR) 0.68, 95% Confidence interval (CI) 0.57-0.81; p<0.001) in patients treated with a combination of ASA and clopidogrel for 21 days compared to ASA alone (13). Similar to the EXPRESS study (3), most of the strokes developed in the initial days following the TIA. The observation that strokes occur very early, as is evident from EXPRESS and CHANCE suggests that perhaps the vascular pathology responsible for the events begins to heal rapidly once antiplatelet therapy is initiated. This allows for the possibility that shorter duration combination antiplatelet therapy may also be as effective as the 21 days treatment in CHANCE or the 30 days treatment in the NIH funded POINT trial. A prospective study that compares the outcome of stroke, MI or death at 90 days in patients treated with 10 days or 30 days of dual antiplatelet therapy will therefore be very useful. If the shorter duration dual antiplatelet therapy is as effective as the longer duration dual antiplatelet treatment, this will result in lower costs and the lower risk of side effects in stroke prevention in high-risk TIA patients.

Hypothesis:

The short duration use of dual antiplatelet agents for 10 days is as effective as a longer duration of 30 days or longer. The shorter duration treatment will however result in fewer hemorrhagic complications.