Table 2.

Randomized clinical trials on aspirin plus clopidogrel at different timing after stroke or TIA.

Trial	Population	Antiplatelet regimen	Primary Endpoints	Major findings
MATCH [36]	7599 high-risk patients with prior (<3 months) ischemic stroke or TIA	Aspirin 325 mg/d plus clopidogrel 75 mg/d versus clopidogrel 75 mg/d alone	Ischemic stroke, MI, vascular death.	Nonsignificant relative risk reduction (6.4%, P = .244) in the primary endpoint in aspirin/clopidogrel group. Increased risk for major or life-threatening bleeding in aspirin/ clopidogrel group (P < .0001)
CHARISMA [37]	15603 patients with established prior CVD (<5 years) or multiple vascular risk factors	Clopidogrel 75 mg/d plus aspirin 75–162 mg/d versus aspirin 75–162 mg/d alone	MI, Stroke, or vascular death.	Nonsignificant relative risk reduction (7%, P = .22) in primary endpoint in aspirin/clopidogrel group. Increased risk for moderate bleeding in clopidogrel/aspirin group (P < .001)
ACTIVE-A [40]	7554 high-risk AF patients, unsuitable for vitamin K antagonists	Clopidogrel 75 mg/d plus aspirin 75–100 mg/d versus placebo plus aspirin 75–100 mg/d	Stroke, MI, systemic embolism, vascular death.	Significant reduction in major vascular events especially stroke (28%, P < .00002) in the aspirin/clopidogrel group. Significant increased risk of major hemorrhage in clopidogrel/aspirin group (58%, P < .0001)
CARESS [41]	107 patients with TIA or ischemic stroke (<3 months) due to carotid artery stenosis and MES on TCD	Clopidogrel 300 mg load, then 75 mg/d plus aspirin 75 mg/d versus aspirin 75 mg/d alone	Proportion of patients with MES at day 7, MES frequency per hour at days 2 and 7	Significant relative risk reduction in both primary (39.8%, P = .0046) and secondary (61.6%, P = .0005 and 61.4%, P = .0013, resp.) endpoints in aspirin/clopidogrel group
FASTER [42]	392 patients with TIA or minor stroke within 24 hours of symptom onset	Clopidogrel 300 mg load, then 75 mg/d plus aspirin 81 mg/d plus simvastatin 40 mg/d versus aspirin (± simvastatin) alone	Any stroke (ischemic or hemorrhagic) within 90 days.	Nonsignificant absolute risk reduction (3.8%, P = .19) in primary outcome among patients with aspirin/clopidogrel. Nonsignificant absolute risk increase (1.0%, P = .5) in rate of intracranial hemorrhage in aspirin/clopidogrel group
CLAIR [43]	100 patients with symptomatic (TIA or stroke within previous 7 days) intra- or extracranial artery stenosis and MES on TCD	Clopidogrel 300 mg load, then 75 mg/d plus aspirin 75–160 mg/d versus aspirin alone for 7 days	Proportion of patients with MES at day 2	Significant relative risk reduction in primary endpoint (42.4%, P = .025) in aspirin/clopidogrel group. 93 of 100 patients had symptomatic intracranial stenosis in either the intracranial internal carotid artery or the middle cerebral artery

Legend: MI: myocardial infarction; TIA: transient ischemic attack; CVD: cerebrovascular disease; AF: atrial fibrillation; MES: microembolic signals; TCD: transcranial Doppler.