Dual Antiplatelet Therapy in Secondary Prevention of Ischemic Stroke: A Ghost from the Past or a New Frontier?

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 pati-; ents with MES at; day 7, MES freque-; ncy 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 (ischem-; ic 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 pati-; ents with MES at day 2.	Significant relative risk reduction in prim-; ary 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.