"Clopidogrel with Aspirin in High-Risk Patients with Acute Non-Disabling Cerebrovascular Events (CHANCE)". The New England Journal of Medicine. 2013.
Links to original sources: Wiki Journal Post Full Journal Article
Does the combination therapy with clopidogrel and aspirin, as compared to aspirin alone, reduce the risk of subsequent stroke in patients with minor ischemic stroke or high-risk TIA when treated within 24 hours after the onset of symptoms?
For patients with high-risk TIA or minor ischemic stroke who are treated within 24 hours after symptom onset, the combination of clopidogrel and aspirin reduces the risk of subsequent stroke without increasing the risk of hemorrhage compared to aspirin alone.
CHANCE was a randomized, controlled trial that showed the benefits of dual antiplatelet therapy with clopidogrel and aspirin in reducing the risk of subsequent stroke in patients with TIA or minor ischemic stroke, which often lead to disabling strokes. The trial was conducted exclusively in China, where stroke rates are higher than in Western countries, and enrolled patients who could start treatment within 24 hours of symptom onset.
Current treatment guidelines for stroke may not fully reflect the results of this trial. As such, treatment with a combination of clopidogrel and aspirin may be considered for patients presenting with TIA or minor ischemic stroke who can be treated within 24 hours after symptom onset.
- Randomized, double-blind, placebo-controlled trial - N=5,170 patients with minor ischemic stroke or high-risk TIA - Combination Therapy: Clopidogrel (300 mg loading dose, then 75 mg/day for 90 days) plus aspirin (75 mg/day for 21 days, then placebo aspirin for the remaining days) - Control: Placebo plus aspirin (75 mg/day for 90 days) - Setting: 114 centers in China - Enrollment: 2009-2012 - Follow-Up: 90 days - Analysis: Intention-to-treat - Primary outcome: Stroke (ischemic or hemorrhagic) during 90 days of follow-up
- Inclusion Criteria: Patients aged 40 years or older, with acute minor ischemic stroke or TIA, able to start study drug within 24 hours after symptom onset - Exclusion Criteria: Hemorrhage, severe stroke, and other specific conditions and contraindications - Baseline Characteristics: Median age 62 years, 33.8% female, 65.7% with hypertension, 21.1% with diabetes, 43.0% current or former smokers
- Patients assigned to either clopidogrel and aspirin or placebo and aspirin - Open-label aspirin given on day 1
- Primary Outcome: Stroke occurred in 8.2% of patients in the combination therapy group, compared with 11.7% in the aspirin group (hazard ratio [HR], 0.68; P<0.001) - Secondary Outcomes: No significant difference in moderate or severe hemorrhage between groups (0.3% in both groups; P=0.73) - Subgroup Analysis: Consistent reduction in stroke across all subgroups with combination therapy
- The study was conducted in China, and results may not be fully generalizable to other populations - It is unclear whether these findings apply to populations with lower rates of large-artery intracranial atherosclerosis
The study was funded by the Ministry of Science and Technology of the People's Republic of China.
Please refer to the New England Journal of Medicine 2013; 369:11-19, NCT00979589 trial registration, and the Supplementary Appendix for more information.