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J Thromb Thrombolysis. 2019 Feb;47(2):233-247. doi: 10.1007/s11239-018-1786-z.

Clopidogrel and aspirin after ischemic stroke or transient ischemic attack: an updated systematic review and meta-analysis of randomized clinical trials.

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Department of Internal Medicine, Hurley Medical Center/Michigan State University, Flint, MI, 48503, USA.
Division of Cardiology, West Virginia University School of Medicine, Morgantown, WV, 26506, USA.
Division of Hematology & Oncology, Ascension St. John Hospital, Grosse Pointe Woods, MI, 48236, USA.
Research Assistance, Flint, MI, 48503, USA.
Division of Cardiology, Hurley Medical Center/Michigan State University, Flint, MI, 48503, USA.
Division of Neurology, Hurley Medical Center/Michigan State University, Flint, MI, 48503, USA.
Brigham and Women's Hospital Heart & Vascular Center, Harvard Medical School, 75 Francis Street, Boston, MA, 02115, USA.


Recurrent stroke is common immediately following a transient ischemic attack (TIA) or ischemic stroke. Dual antiplatelet therapy (DAPT) with clopidogrel and aspirin may provide greater protection against subsequent stroke than monotherapy. Electronic databases were searched for randomized clinical trials (RCTs) comparing DAPT with monotherapy in ischemic stroke/TIA. Sixteen RCTs with a total of 29,032 patients were included. Compared with monotherapy, DAPT was associated with significantly lower rates of any stroke (risk ratio [RR] 0.80; 95% confidence interval [CI] 0.72-0.89) and ischemic stroke (RR 0.75; 95% CI 0.66-0.85) during any follow-up period. Although significant increases in intracranial bleeding (RR 1.55; 95% CI 1.20-2.01) and major bleeding (RR 1.90; 95% CI 1.33-2.72) were associated with DAPT, especially with long-term follow-up, the number needed to harm was 258 and 113, respectively. Nevertheless, short-duration DAPT (≤ 1 month) started during the early acute ischemic phase was associated with less bleeding than longer DAPT and greater reduction of recurrent strokes compared with monotherapy. In contrast, long DAPT and DAPT started later after the index event (≥ 1 month) were associated with similar rates of any stroke and increased risks of bleeding compared with monotherapy. Other clinical outcomes were essentially similar between the two groups and included recurrent TIA (RR 0.88; 95% CI 0.72-1.07), myocardial infarction (RR 1.04; 95% CI 0.84-1.29), vascular death (RR 0.99; 95% CI 0.82-1.19), and any death (RR 1.12; 95% CI 0.88-1.42). Similar findings were observed in patients who presented with minor stroke/TIA. Conclusions: Among patients who presented with ischemic stroke/TIA, short-course clopidogrel plus aspirin immediately following the index event appears to be more effective than and as safe as monotherapy for secondary stroke prevention.


Acute stroke; Aspirin; Clopidogrel; DAPT; Ischemic stroke; Meta-analysis; TIA

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