UMEM Educational Pearls

Category: Neurology

Title: Early Dual Antiplatelet Therapy for Stroke Prevention?

Keywords: stroke, TIA, antiplatelet, aspirin, clopidogrel, POINT, CHANCE (PubMed Search)

Posted: 10/10/2018 by WanTsu Wendy Chang, MD
Click here to contact WanTsu Wendy Chang, MD

Question

Does using a combination of aspirin and clopidogrel decrease your patient’s risk of recurrent stroke after a minor ischemic stroke or high risk TIA event?

The recent international Platelet-Oriented Inhibition in New TIA and Minor Stroke (POINT) trial compared 4881 patients receiving aspirin/clopidogrel vs. aspirin/placebo within 12 hours of symptom onset.
- Patients who received DAPT had a lower rate of major ischemic events at 90 days compared to aspirin/placebo (5.0% vs. 6.5%, p=0.02).
- However, patients who received DAPT had a higher rate of major hemorrhage compared to aspirin/placebo (0.9% vs. 0.4%, p=0.02).
A similar Chinese study, the Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events (CHANCE) trial, compared 5170 patients receiving DAPT vs. aspirin/placebo within 24 hours also found lower rate of stroke (8.2% vs. 11.7%, p<0.001) but similar rates of moderate/severe hemorrhage (0.3% vs. 0.3%, p=0.73).
Major differences between these two trials are the population studied and the duration of DAPT, as POINT utilized DAPT for 90 days while CHANCE utilized DAPT for 21 days.

Bottom Line: The use of DAPT in minor ischemic stroke and high risk TIA reduces the risk of recurrent stroke. However, the duration of DAPT may affect the risk of major hemorrhage.

Answer

Trial	POINT (Johnston et al, NEJM 2018)	CHANCE (Wang et al, NEJM 2013)
Location	N. America, Europe, Australia, New Zealand (82.8% enrolled in the US)	China
Population	Age ≥ 18 Within 12 hours of sympton onset NIHSS ≤ 3 or TIA with ABCD ≥ 4	Age ≥ 40 Within 24 hours of symptom onset NIHSS ≤ 3 or TIA with ABCD ≥ 4
Study Group	Clopidogrel 600mg load, then 75mg daily x 90 days + Aspirin 50-325mg daily x 90 days	Clopidogrel 300mg load, then 75mg daily x 90 days + Aspirin 75mg daily x 21 days
Control Group	Aspirin 50-325mg daily x 90 days + Placebo	Aspirin 75mg daily x 90 days + Placebo
Primary Efficacy Outcome	Major ischemic event defined as cardiovascular death, stroke, MI	Stroke (ischemic or hemorrhagic)
Primary Safety Outcome	Major hemorrhage defined as symptomatic ICH, intraocular bleeding causing vision loss, transfusion ≥ 2 units PRBCs, hospitalization/death related to hemorrhage	Moderate hemorrhage defined as transfusion requirement Severe hemorrhage defined as fatal, ICH, hemodynamic compromise

References

Johnston SC, Easton JD, Farrant M, et al. Clopidogrel and aspirin in acute ischemic stroke and high-risk TIA. N Engl J Med2018; 379(3):215-25.
Wang Y, Wang Y, Zhao X, et al. Clopidogrel with aspirin in acute minor stroke or transient ischemic attack. N Engl J Med 2013;369(1):11-9.

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