article286

CHANCE

Clinical Question

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?

Bottom Line

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.

Major Points

Guidelines

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.

Design

- 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

Population

- 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

Interventions

- Patients assigned to either clopidogrel and aspirin or placebo and aspirin
- Open-label aspirin given on day 1

Outcomes

- 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

Criticisms

- 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

Funding

The study was funded by the Ministry of Science and Technology of the People's Republic of China.