Dosage

For secondary stroke prevention extended release dipyridamole 200 mg plus ASA 25 mg should be dosed a one capsule twice daily without regard to meals. No dosage adjustment is required in mild to moderate renal or hepatic dysfunction.

Mechanism of Action

Aggrenox is a combined medication containing 200 mg of extended release dipyridamole and 25 mg of immediate release ASA. The antithrombotic effect is the result of the combined effect of both components. The mechanism of action of ASA is described in the section on acetylsalicylic acid. The antiplatelet effect of dipyridamole is controversial. Dipyridamole is known to inhibit the uptake of adenosine into platelets resulting in increased levels of intracellular cyclic adenosine monophosphate (cAMP), an inhibitor of platelet aggregation. cAMP levels are also increased by inhibition of cyclic nucleotide phosphodiesterase (PDE), reducing its degradation.

Secondary Prevention of Cerebrovascular Disease

Two large randomized trials demonstrated the combination of ER dipyridamole and ASA is considerably better than ASA or ER dipyridamole alone in preventing recurrent stroke in patients with TIA or previous stroke. Another trial directly comparing the combination of ER dipyridamole and ASA with clopidogrel demonstrated equipoise between the efficacies of the two agents, although clopidogrel was associated with a lower rate of intra-cerebral hemorrhage.

Recommendations

Patients who sustain a TIA or ischemic stroke of noncardiac origin should be treated with an antiplatelet agent (Class I, Level A). Initial therapy should be ASA 75-162 mg once daily, clopidogrel 75 mg once daily, or ER dipyridamole 200 mg twice daily plus ASA 25 mg twice daily (Class I, Level A). The choice of antiplatelet therapy regimen is determined by consideration of cost, tolerance, and other associated vascular conditions.

Warnings & Special Considerations

Headache is commonly seen in patients taking Aggrenox. This tends to be worse early in the course of treatment and may be minimized by an alternated regimen of one capsule in the evening and 75 to 162 mg of ASA in the morning for the first week of treatment.