Clopidogrel Versus Dipyridamole in Addition to Aspirin in Reducing Embolization Detected With Ambulatory Transcranial Doppler

Abstract

After stroke and transient ischemic attack there is a high early risk of recurrent stroke, particularly in large artery disease. It has been suggested more intensive antiplatelet regimens are required, but trial data are lacking. Treatment efficacy can be evaluated using transcranial Doppler detection of embolic signals. Ambulatory transcranial Doppler has recently been developed; prolonged recording may reduce subject numbers required to determine therapeutic efficacy. In a randomized trial (ISRCTN68019845) with blinded end point evaluation, we determined whether treatment with dipyridamole or clopidogrel, in addition to aspirin, was more effective at reducing embolization. Consecutive patients with recent symptomatic carotid stenosis were recruited. Ambulatory transcranial Doppler and platelet aggregometry were performed at baseline and 48 hours. Patients, all on aspirin, were randomized to dipyridamole or clopidogrel. Recordings were analyzed offline masked to subject identity. Sixty patients were recruited, 30 in each arm. The primary end point of change in embolic signal frequency did not differ between groups (P=0.36). In patients with embolic signals at baseline, there was no difference in reduction in embolic signal frequency: dipyridamole (75.5; SD 17.7%) versus clopidogrel (77.5; SD 20.5%; P=0.77). Baseline platelet aggregation was not different between regimens, but at 48 hours, adenosine 5'-diphosphate aggregation rate (but not collagen) was lower with clopidogrel (P<0.001). Both dipyridamole and clopidogrel reduced embolization to a similar extent. Embolic signals are strong predictors of future stroke rate in this patient group. Our results suggest these 2 treatment regimens have similar efficacy in early secondary prevention of stroke, although this now needs testing in large Phase III trials.