• • Population 

    • Inclusion: > 40 y/o, acute minor ischemic stroke (<3 on NIHSS) or  high-risk TIA, able to start medications within 24hrs of symptom onset

    • Exclusion: hemorrhage,  vascular malformation, tumor, abscess, or other major nonischemic brain disease; isolated sensory symptoms (e.g., numbness), isolated visual changes, or isolated dizziness or vertigo without evidence of acute infarction on baseline CT or MRI of the head, preMRS >2, NIHSS >4, indication for AC such as afib, heparin or AC within 10 days, taking antiplatelet or NSAIDS, GIB within 3 months, planned revascularization, life expectancy <3 months

    • Number Enrolled: 5170

  • Interventions 

    • Control: Aspirin (75-300mg) 

    • Treatment: aspirin 75mg daily days 2-21 and clopidogrel 300mg loading followed by 75mg for 90 days  

    • No patient did not receive thrombolysis 

  • Results

    • Stroke occurred in 8.2% in treatment group vs 11.7% in control (p=<0.001, HR 0.68) at 90 days

      • Fatal or disabling stroke occurred in 5.2% of treatment vs 6.8% in control (P=0.01, HR 0.75)

      • Ischemic stroke occurred 7.9% in treatment vs 11.4% in control (P=0<.001, HR 0.67)

      • Hemorrhagic stroke occurs in 0.3% of both groups

    • Vascular events occurred in 8.4% of treatment and 11.9% of control (p<0.001, HR 0.69) at 90 days

      • Vascular death occurred in 0.2% of both groups

      • Death from any cause occurred in 0.4% of both groups

      • TIA occurred in 1.5% of treatment and 1.8% of control (p=0.36)

    • Moderate to severe bleeding (per GUSTO criteria) occurred in 0.3% of both groups at 90 days

      • Any bleeding event occurred 2.3% in treatment and 1.6% in control (p=0.09, HR 1.41)

    • Number needed to treat is 29 for aspirin and clopidogrel compared to aspirin alone

  • Outcome

    • Aspirin and clopidogrel should be given to patients with high-risk TIA (ABCD2 4<) or minor ischemic stroke (NIHSS <3) to prevent subsequent strokes within 90 days.

    • Aspirin and clopidogrel are safe to be given together as compared to aspirin alone.

• • Population 

    • Inclusion: >18 y/o, Ischemic stroke with NIHSS <3 or high-risk TIA within 12 hours, no intracranial bleed on CT or MRI,  

    • Exclusion: Isolated numbness, vertigo, vision changes, any thrombolytic within 1 week, receipt of thrombolysis, endovascular therapy or endarterectomy, need for anticoagulation, had anticipated use of an NSAID for more than 7 days during the trial period 

    • Number Enrolled: 2432 in treatment group vs 2449 in placebo group

  • Interventions 

    • Clopidogrel (600mg load + 75mg qd) and aspirin (50-325mg qd) vs placebo and aspirin for 90 days

  • Results

    • Major ischemic event (ischemic stroke, myocardial infarction, or death from ischemic vascular causes) occurred in 5% of treatment group and 6.5% of the control group within 90 days(p=0.02)

    • Ischemic stroke at 90 days: 4.6% in treatment group, 6.3% in control (p=0.01)

    • Major hemorrhage: 0.9% of treatment vs 0.4% of control (p=0.02)

      • Minor hemorrhage: 1.6% of treatment vs 0.5% of control (p=0.002)

    • The benefit of clopidogrel plus aspirin was greater in the first 7 days (p=0.04) and in the first 30 days (p=0.02) than at 90 days

      • the risk of hemorrhage with clopidogrel plus aspirin versus aspirin alone was greater during the period from 8 to 90 days (p=0.04) than during the first 7 days (p=0.34)

  • Outcome

    • Patients with minor ischemic stroke or high-risk TIA treated with Clopidogrel and aspirin had lower rates of ischemic stroke but higher risk of hemorrhage than those taking aspirin alone

Population: 

• Inclusion: >18 y/o, NIHSS <5, No more than 1 point on any part of the NIHSS, Alert, stroke identified on CTH or MRI, could start treatment within 4.5hrs 

• Exclusion: preMRS >2, history of ICH, need for anticoagulation, disabling deficit 

• Treatment group n=393 vs alteplase n=367

Intervention:

•  Clopidogrel 300mg qd and aspirin 100mg qd for 10-14 days vs alteplase 0.9mg/kg

  • Both groups given "standard guideline-based treatment" up to 90 days

Results:

• mRS 0 or 1 at 90 days was 93.8% in treatment vs 91.4% in control (p=<0.001 for noninferiority)

• Fewer patients had early neurologic deterioration within 24 hours in treatment group: Risk Difference unadjusted -4.5%, adjusted -4.6%

  •  One patient experienced sICH and 6 patients experienced other bleeding events in the DAPT group, while 3 patients experienced sICH and 19 patients experienced other bleeding events in the alteplase group 

Outcome:

• In patients with nondisabling minor acute ischemic stroke, DAPT is noninferior to alteplase when administered within 4.5hrs of stroke onset in terms of excellent functional outcome at 90 days

• • Population - 

    • Inclusion: >18 y/o, NIHSS 4-10, premRS <1,  Ischemic stroke identified on MRI or CT

    • Exclusion: Thrombolysis or endovascular therapy, indication for anticoagulation, history of ICH, planned carotid revascularization, GI or urinary bleed in the last 3 months

    • Number Enrolled: n=3005 enrolled, 1541 in clopidogrel + aspirin vs 1459 on aspirin alone

  • Interventions - 

    • Clopidogrel (300mg load then 75mg qd) + aspirin (100mg qd) x14 days followed by clopidogrel 75ng qd or aspirin 100mg qd day 15-90 vs aspirin 100-300mg qd for 14 days then aspirin 100mg qd days 15-90

  • Results

    • Primary: Neurologic deterioration at 7 days

      • 71/1502 (4.8%) in clopidogrel + aspirin vs 95/1413 (6.7%) in the control (p=-0.03)

    • Secondary outcomes:

      • mRS of 0-1 at 90 days: 1130/1470 (76.9%) in clopidogrel + aspirin vs 1015/1361 (74.6%) in aspirin alone (p=0.14)

      • Change in NIHSS at 14 days: -0.56 in clopidogrel + aspirin vs 0 in aspirin alone p=0.89

      • New stroke within 90 days: 12/1470 (0.8%) in clopidogrel + aspirin vs 13/1361 (1%.0) in aspirin alone (p=0.67)

      • Hemorrhagic stroke: 1/1470 (0.1%) in clopidogrel + aspirin vs 2/1361(0.1%) in aspirin alone (p=0.52)

      • All cause death: 16/1471 (1.1%) in clopidogrel + aspirin vs 12/1361 (0.9%) in aspirin alone (p=0.59)

    • No statistically significant differences were found between % of excellent functional outcomes, change in NIHSS at 14 days, new stroke within 90 days, rates of hemorrhagic stroke, vascular events, hemorrhage of any kind including mucocutaneous, organ and intracranial. 

  • Outcome

    • Patients with mild to moderate ischemic stroke who are not eligible for thrombolytics or endovascular repair would benefit from clopidogrel + aspirin for 2 weeks followed by monotherapy as compared to aspirin alone in terms of preventing neurologic deterioration at 7 days. 

    • No statistically significant benefit was shown in terms of % of excellent functional outcomes, change in NIHSS at 14 days, new stroke within 90 days, rates of hemorrhagic stroke, vascular events, hemorrhage of any kind including mucocutaneous, organ and intracranial.