Aspirin and Clopidogrel Loading in Acute Ischemic Stroke

The administration of clopidogrel alone or in combination with aspirin is not recommended for the treatment of acute ischemic stroke. 1

Recommendations for Antiplatelet Therapy in Acute Stroke

Oral administration of aspirin (initial dose 160-325 mg) within 24 to 48 hours after stroke onset is recommended for most patients with acute ischemic stroke 1
Aspirin administration provides a small but statistically significant reduction in mortality and morbidity when started within 48 hours of stroke onset 1
The primary benefit of aspirin appears to be reduction of early recurrent stroke rather than limitation of neurological consequences of the initial stroke 1

The administration of clopidogrel alone or in combination with aspirin is not recommended for the treatment of acute ischemic stroke (Class III, Level of Evidence C) 1
Only in patients with minor stroke (NIHSS ≤3) or high-risk TIA (ABCD2 ≥4) is dual antiplatelet therapy with aspirin and clopidogrel recommended, initiated within 24 hours of symptom onset 1
For patients with minor stroke, DAPT should be limited to 21 days followed by long-term single antiplatelet therapy 1

While some pilot studies have suggested safety of loading with aspirin and clopidogrel in acute stroke 2, larger trials have not demonstrated clear superiority of combination therapy over aspirin alone in general acute stroke populations 3
The LOAD pilot study showed potential safety of loading with 375 mg clopidogrel and 325 mg aspirin within 36 hours of stroke onset, but this was a small study with only 40 patients 2
A more recent trial found that clopidogrel plus aspirin was not superior to aspirin alone for preventing new ischemic lesions in patients with acute stroke caused by large artery atherosclerosis 3

Dual antiplatelet therapy is associated with an increased risk of bleeding compared to aspirin monotherapy 4
A meta-analysis showed DAPT was associated with a significantly increased risk of moderate or severe bleeding (RR: 1.88; 95% CI: 1.10-3.23) compared to aspirin alone 4
The administration of aspirin as adjunctive therapy within 24 hours of thrombolytic therapy is not recommended (Class III, Level of Evidence A) 1

For patients who have received IV thrombolysis (rtPA), aspirin administration should generally be delayed until 24 hours later 1
In patients with impaired swallowing, rectal aspirin (325 mg) or aspirin (81 mg) or clopidogrel (75 mg) via enteral tube are reasonable alternatives 1
The 2018 AHA/ASA guidelines introduced a new recommendation for dual antiplatelet therapy, but only for minor stroke or high-risk TIA, not for all acute strokes 1

For most patients with acute ischemic stroke, aspirin monotherapy (160-325 mg) should be initiated within 24-48 hours after stroke onset 1
Aspirin should not be considered a substitute for other acute interventions such as IV rtPA 1
Dual antiplatelet therapy with aspirin and clopidogrel loading is not recommended for routine treatment of acute ischemic stroke 1
Only in the specific subset of patients with minor stroke (NIHSS ≤3) or high-risk TIA should DAPT be considered, and then only for a limited duration of 21 days 1