1. Rikki Weems, PGY III August 20, 2015
LSU Journal Club Clopidogrel with Aspirin in Acute Minor Stroke or Transient Ischemic Attack (CHANCE trial: Clopidogrel in High-risk patients with Acute Nondisabling Cerebrovascular Events) Y. Wang MD, et al.
Rikki Weems, PGY III
August 20, 2015

2. Background
Risk of subsequent stroke after TIA or minor disabling stroke is high, especially in the first three months (10-20% )
Use of aspirin after TIA/CVA for secondary stroke prevention is well established
Aspirin and clopidogrel synergistically inhibit platelet aggregation

3. Background
Aspirin and clopidogrel synergistically inhibit platelet aggregation

4. Background
Dual antiplatelet therapy reduces the risk of ischemic events in patients with acute coronary syndromes
Trials looking at DAPT as secondary prevention of stroke have failed to show benefit
Did not study early, high-risk period
Included patients with moderate to severe CVA (higher risk of hemorrhagic transformation)
Included only few patients with TIA

5. Research question
Is the addition of clopidogrel to aspirin therapy in the early post-acute TIA/Stroke period more effective at preventing recurrent stroke than aspirin alone, and is it safe?

6. Study design Randomized, double-blinded placebo-controlled trial
114 Clinical centers in China
5170 patients Randomized into two groups:
DAPT: Aspirin + Clopidogrel x 21 days, then clopidogrel alone (with placebo)
ASA: Aspirin + Placebo

7. Study Subjects Inclusion: Age ≥ 40 High risk TIA with ABCD2 score ≥ 4
Acute minor ischemic CVA with NIHSS ≤ 3
Able to start therapy within 24 hours of symptom onset

8. Study Subjects Exclusion:
Symptoms attributable to non-ischemic event: hemorrhagic stroke, vascular malformation, tumor, abscess
Isolated vision deficit, sensory deficit, or dizziness
Clear indication for anti-coagulation therapy (afib, suspect hypercoagulable state)
Contraindication to aspirin or clopidogrel (allergy, etc)
GI bleed or major surgery in past 3 months
Planned/probable surgery in next 3 months
Heparin or oral anticoagulant use in last 10 days
TIA/Stroke caused by angiography or surgery
Life expectancy less than 3 months
Childbearing age without negative pregnancy test, and not on contraceptive

9. Study Subjects 41,561 patients screened, 5170 enrolled Mean age 62
2584 DAPT group, 2586 ASA group
Mean age 62
67% Male, 33% Female
Comorbidities: 2/3 HTN, 1/2 smokers, 1/5 DM
Index event: 1/3 TIA, 2/3 CVA

10. Study design Primary efficacy outcome: new stroke event at 90 days
Primary safety outcome: new moderate-to-severe bleeding event
Severe: life-threatening, hemodynamically unstable
Moderate: requires transfusion, but HD stable

11. Results
New stroke occurred in 212 (8.2%) of A+C group and 302 (11.7%) of A group. P < 0.001, HR 0.68
Relative Risk reduction of 32%, NNT= 29

12. Results
New stroke occurred in 212 (8.2%) of A+C group and 302 (11.7%) of A group. P < 0.001, HR 0.68
Relative Risk reduction of 32%, NNT= 29

13. Results
Moderate or severe hemorrhage occurred in 7 (0.3%) of A+C group and 8 (0.3%) of the A group
Rate of any bleeding was 2.3% A+C, 1.6% A (p = 0.09)

14. Conclusions
“Among patients with high-risk TIA or minor ischemic stroke who are initially seen within 24 hours after symptom onset, treatment with clopidogrel plus aspirin for 21 days, followed by clopidogrel alone for a total of 90 days, is superior to aspirin alone in reducing the risk of subsequent stroke events. The combination of clopidogrel with aspirin did not cause more hemorrhagic events in this patient population than aspirin alone”

15. Conclusions
Major benefit is seen in the first hours, new stroke events are similar after first few days.
Treatment with aspirin and clopidogrel as soon as possible after symptom onset is likely to produce the greatest absolute benefit

16. Limitations External validity
Can these results be translated into our patient population?
Distribution of stroke subtypes in China different than in more developed countries; China has higher incidence of intracranial large-artery atherosclerosis.
Rates of treatment of HTN, DMII, and HLD are much lower in China compared to US & Europe

17. Future Research
POINT trial (Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke)
NIH trial enrolling patients in North America, Europe, and Australia, very similar model to CHANCE trial