PDF: CHANCE
(2013)Objective
Clopidogrel plus aspirin versus aspirin alone in reducing the risk of recurrent stroke in patients with minor stroke or high-risk TIA.
Study Summary
• The CHANCE trial demonstrated that clopidogrel plus aspirin initiated within 24 hours of symptom onset significantly reduced the risk of recurrent stroke within 90 days, without increasing the risk of major bleeding, compared to aspirin monotherapy..
Intervention
Clopidogrel (300 mg loading dose, then 75 mg daily for 90 days) plus aspirin (75 mg daily for 21 days) vs. aspirin alone (75 mg daily for 90 days).
Inclusion Criteria
Patients aged ≥40 years with acute minor ischemic stroke (NIHSS ≤3) or high-risk TIA (ABCD2 score ≥4), presenting within 24 hours of symptom onset.
Study Design
Arms: Clopidogrel + Aspirin vs. Aspirin Alone
Patients per Arm: Clopidogrel + Aspirin: 2584, Aspirin Alone: 2591
Outcome
• Stroke within 90 days: 8.2% (dual therapy) vs 11.7% (aspirin), HR 0.68 (95% CI 0.57–0.81), P<0.001. <br>• Ischemic stroke: 7.9% vs 11.4%. <br>• Moderate or severe hemorrhage: 0.3% vs 0.3%. <br>• Combined vascular events: 8.4% vs 12.0%. <br>• No significant difference in moderate-to-severe bleeding between groups..
Bottom Line
Early dual antiplatelet therapy reduced 90-day stroke recurrence without increasing major bleeding risk.
Major Points
- Landmark trial establishing dual antiplatelet therapy (DAPT) for acute minor stroke and high-risk TIA. 5170 patients randomized within 24 hours of symptom onset at 114 Chinese centers.
- DAPT regimen: clopidogrel 300 mg loading dose on day 1 + aspirin, then clopidogrel 75 mg/day for 90 days. Aspirin was given at 75–300 mg on day 1, then 75 mg/day for the first 21 days only — discontinued at day 21 (CHANCE uniquely tapered aspirin early).
- Primary outcome (any stroke at 90 days): 8.2% vs 11.7% (HR 0.68, 95% CI 0.57–0.81, P<0.001). ARR = 3.5%, RRR = 30%, NNT = 29.
- No significant increase in major or moderate bleeding (0.2% vs 0.2% for severe/moderate hemorrhage). Total bleeding events: 2.3% vs 1.6% (P=0.09).
- Exclusively Chinese population — CYP2C19 loss-of-function alleles are more prevalent in East Asians (~60% carry at least one), which affects clopidogrel metabolism.
- POINT trial (2018) later confirmed DAPT efficacy in a Western population (minor stroke or high-risk TIA within 12 hours) but showed higher major bleeding (0.9% vs 0.4%), leading to combined CHANCE-POINT meta-analysis supporting 21-day DAPT as optimal duration.
- CHANCE-2 (2021) subsequently showed ticagrelor + aspirin was superior to clopidogrel + aspirin in CYP2C19 loss-of-function carriers.
Study Design
- Study Type
- Randomized, double-blind, placebo-controlled
- Randomization
- Yes
- Blinding
- Double-blind
- Sample Size
- 5170
- Follow-up
- 90 days
- Centers
- 114
- Countries
- China
Primary Outcome
Definition: Stroke at 90 days
| Control | Intervention | HR/OR | P-value |
|---|---|---|---|
| 11.7% | 8.2% | 0.68 (0.57–0.81) | <0.001 |
Limitations & Criticisms
- Exclusively Chinese population — limits generalizability to non-Asian populations. CYP2C19 loss-of-function alleles (poor metabolizers) are ~15–20% in East Asians vs ~2–5% in Europeans, affecting clopidogrel efficacy differently.
- Short follow-up (90 days) — cannot assess long-term bleeding risk of extended DAPT.
- Aspirin dose was low (75 mg maintenance) — different from SPS3 (325 mg) and Western practice.
- No mandatory vascular imaging — stroke etiology (large artery vs lacunar vs cardioembolic) not systematically classified, raising concern about mixed etiologies.
- Under-treatment of comorbidities — only 10.9% had hyperlipidemia documented at baseline despite mean age 62 with high smoking rates.
- High TIA proportion (28.2%) with ABCD2 ≥4 threshold — ABCD2 has modest predictive accuracy for stroke recurrence.
- No CYP2C19 genotyping in original trial — CHANCE-2 later showed genotype-guided therapy was superior in LOF carriers.
Citation
Wang Y, et al. N Engl J Med. 2013;369(1):11–19.