Dipyridamole plus aspirin: the best regimen for stroke prevention after noncardioembolic focal cerebral ischemia.

study [8–10] proves otherwise. Therefore, based on a combination of currently available direct and indirect evidence, dipyridamole plus aspirin is the proper recommendation: it is not statistically in the best interests of the patient to prescribe monotherapy with either aspirin or clopidogrel. The only issue we see here is: which formulation of dipyridamole should be employed? We shall present evidence for conventional dipyridamole 225 mg daily rather than extended-release dipyridamole 400 mg daily. We raise this issue for the following reasons: • We fi nd that the proprietary formulation of 200 mg of extended-release dipyridamole produces objectionable headache in many patients, even when treatment is begun with one dose rather than two daily. • In contrast, it is relatively easy to avoid objectionable headache in most patients by building toward 225 mg daily of conventional dipyridamole through the use of 25 or 75 mg tablets. • A nonrandom sampling of retail cost in the United States (at www.drugstore.com, www.americarx.com, www.cvs.com, and two New York metropolitan area retail pharmacy chain stores) of a 30-day supply of the extended-release dipyridamole-aspirin combination as of January 18, 2006 gave a range of USD 121.99– 164.99, compared with USD 17.39–56.71 for conventionally formulated generic dipyridamole 225 mg (as 75 mg tablets) daily (plus a negligible cost for aspirin). In this issue of Cerebrovascular Diseases , Sacco et al. [1] report subgroup analyses for the previously reported Warfarin-Aspirin Recurrent Stroke Study (WARSS) [2] . They conclude that antiplatelet therapy rather than warfarin ‘should be the mainstay of secondary stroke prevention after noncardioembolic stroke’. They go on to agree with the Antithrombotic Trialists’ Collaboration’s recommendation [3] of ‘the use of aspirin, extended-release dipyridamole plus aspirin, and clopidogrel as acceptable options for secondary stroke prevention after noncardioembolic TIA or stroke’. Our meta-analysis of the WARSS, WASID [4] and the warfarin vs. aspirin study of Garde et al. [5] ( table 1 ) leads us to agree fully that antiplatelet treatment should be the mainstay of secondary stroke prevention. However our meta-analyses of antiplatelet treatments lead us to conclude that the three antiplatelet options are not equally effi cacious; rather, the combination of dipyridamole and aspirin is clearly superior to antiplatelet monotherapy, and should be the default recommendation for secondary stroke prevention after prior noncardioembolic TIA or stroke. We note ( table 1 ) that extended-release dipyridamole plus aspirin is clearly superior (relative risk of stroke, RR = 0.762; p = 0.006) to aspirin alone (ESPS2 [6] ), but that clopidogrel was shown not statistically signifi cantly better than aspirin (CAPRIE study [7] ). Thus, the available indirect evidence favors dipyridamole plus aspirin over clopidogrel, until and unless the ongoing PRoFESS Published online: March 27, 2006