Abstract
BackgroundIn patients with ischemic stroke of non-cardioembolic origin, acetylsalicylic acid, clopidogrel, or a combination of acetylsalicylic acid and dipyridamole are recommended for the prevention of a recurrent stroke. The purpose of this study was to examine the risk of bleeding or recurrent stroke associated with these three treatments.MethodsPatients who were discharged with first-time ischemic stroke from 2007–2010, with no history of atrial fibrillation were identified from Danish nationwide registries. Hazard ratios (HRs) and 1-year risks of recurrent ischemic stroke and bleeding were calculated for each antiplatelet regimen.ResultsAmong patients discharged after first-time ischemic stroke, 3043 patients were treated with acetylsalicylic acid, 12,295 with a combination of acetylsalicylic acid and dipyridamole, and 3885 with clopidogrel. Adjusted HRs for clopidogrel versus the combination of acetylsalicylic acid and dipyridamole were 1.02 (95 % confidence interval [CI]: 0.89–1.17) for ischemic stroke and 1.06 (95 % CI: 0.83–1.35) for bleeding. Adjusted HRs for acetylsalicylic acid versus the combination of acetylsalicylic acid and dipyridamole were 1.48 (95 % CI: 1.31–1.67) for stroke and 1.47 (95 % CI: 1.18–1.82) for bleeding. Clopidogrel versus acetylsalicylic acid yielded HRs of 0.69 (95 % CI: 0.59–0.81) and 0.72 (95 % CI: 0.55–0.96) for stroke and bleeding, respectively. The 1-year predicted risks associated with acetylsalicylic acid, the combination of acetylsalicylic acid and dipyridamole, and clopidogrel were 11.1 (95 % CI: 10.2–12.2), 7.7 (95 % CI: 7.3–8.3), and 8.0 (95 % CI: 6.9–8.7) for ischemic stroke, respectively; while, the risks for bleeding were 3.4 (95 % CI: 2.8–3.9), 2.4 (95 % CI: 2.1–2.7), and 2.4 (95 % CI: 1.9–2.9), respectively.ConclusionClopidogrel and the combination of acetylsalicylic acid and dipyridamole were associated with similar risks for recurrent ischemic stroke and bleeding; whereas acetylsalicylic acid was associated with higher risks for both ischemic stroke and bleeding. The latter finding may partially be explained by selection bias.
Highlights
In patients with ischemic stroke of non-cardioembolic origin, acetylsalicylic acid, clopidogrel, or a combination of acetylsalicylic acid and dipyridamole are recommended for the prevention of a recurrent stroke
Of the 42,295 patients included after a first-time ischemic stroke, 19,223 remained after exclusion of patients with atrial fibrillation, those taking oral anticoagulants, and patients not receiving any antithrombotic treatment
Patients receiving acetylsalicylic acid alone had more hypertension, renal disease, chronic obstructive pulmonary disease, and previous bleeding than patients treated with the combination of acetylsalicylic acid and dipyridamole or clopidogrel
Summary
In patients with ischemic stroke of non-cardioembolic origin, acetylsalicylic acid, clopidogrel, or a combination of acetylsalicylic acid and dipyridamole are recommended for the prevention of a recurrent stroke. Treatment with clopidogrel was as effective in preventing ischemic stroke as the combination of acetylsalicylic acid and dipyridamole, and was associated with a lower risk of bleeding [8]. Since the combination of acetylsalicylic acid and dipyridamole was associated with a lower risk of recurrent stroke than acetylsalicylic acid alone and clopidogrel was not significantly different from acetylsalicylic acid, it was surprising that there was no significant difference between clopidogrel and the combination of acetylsalicylic acid and dipyridamole This paradox may be due to differences between study designs, such as inclusion criteria and drug dosage [9]
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