Dual Antiplatelet Therapy for Prevention of Recurrent Ischemic Events

Jean Nappi, PharmD, Fccp, Bcps; Robert Talbert, PharmD, Fccp, Bcps

Disclosures

Am J Health Syst Pharm. 2002;59(18) 

In This Article

Stroke Trials

Early stroke trials evaluating the combination of aspirin (325-1000 mg/day) plus dipyridamole (225-300 mg/day) did not demonstrate a benefit over aspirin alone.[80,81] In the Accidents Ischémiques Cérébraux Liés à l'Athérosclérose (AICLA) trial, 604 patients with TIAs or small cortical strokes were randomized to receive aspirin 1000 mg/day, aspirin 1000 mg/ day plus dipyridamole 225 mg/day, or placebo.[80] Results demonstrated a 42% reduction in the risk of stroke with aspirin versus placebo; no additive benefit was seen with the combination.[78] Similarly, the American-Canadian Co-Operative Study Group found that the addition of dipyridamole to aspirin therapy "contributed nothing" in terms of lowering the frequency of cerebral or retinal infarction or death in patients with a history of recent TIA.[81] The first European Stroke Prevention Study (ESPS-1) found significant benefit from the combination of aspirin 990 mg/day plus standard-release formulation dipyridamole 225 mg/day compared with placebo in 2500 patients with a history of stroke, TIA, or reversible ischemic neurologic deficit.[90] There was an overall reduction of 33% in the risk of stroke and death and a 38% reduction in the risk of stroke alone in patients receiving the aspirin plus dipyridamole combination. ESPS-1 did not compare the effects of monotherapy with combination therapy.[55]

ESPS-2 compared the combination of aspirin (50 mg/day) plus modified-release dipyridamole (400 mg/day) with either agent alone or placebo in 6602 patients with cerebrovascular disease.[53] Primary study endpoints were stroke, death and stroke, or death. The relative-risk reduction for stroke was 18.1% for aspirin (p = 0.013), 16.3% for dipyridamole (p = 0.039), and 37% for the combination when compared with placebo (p < 0.001). When dipyridamole plus aspirin was compared with aspirin alone, the relative-risk reduction for stroke was 23.1% (p < 0.006). Combination treatment showed no benefit for the primary endpoint of death or the secondary endpoint of MI. Bleeding occurred more frequently in both aspirin groups (aspirin alone = 8.2%, aspirin and dipyridamole = 8.7%) when compared with placebo (4.5%) (p = 0.001). However, patients in the dipyridamole groups withdrew from the study most frequently (approximately 29%) with headache and GI events, which were identified as the most common reasons for study withdrawal.[21,53] Low-dose aspirin therapy in this study may have reduced adverse GI effects but may not have had a protective effect in all patients. The combination of aspirin 25 mg and extended-release dipyridamole 200 mg has been approved by FDA for stroke prevention in persons with a history of TIA or ischemic stroke.[52]

Combination therapy with ticlopidine and aspirin has a more potent antiplatelet-aggregating effect in stroke patients than either agent used alone.[91,92] The combination of clopidogrel and aspirin also has been shown to enhance inhibition of platelet aggregation and maintain or improve the degree of platelet aggregation inhibition to a greater extent than ticlopidine plus aspirin.[77] Therefore, the combination of clopidogrel and aspirin may be preferable in the secondary prevention of ischemic events.

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