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Clinical Question
Does adding clopidogrel to aspirin following a transient ischemic attack or minor stroke safely improve outcomes?
Bottom line
This study provides support for a strategy of adding clopidogrel to aspirin for the first week or so after a minor ischemic stroke or transient ischemic attack (TIA) as this is when the greatest benefit occurs. Harms were spread fairly evenly throughout the study period. 1b
Reference
Study design: Randomized controlled trial (double-blinded)
Funding: Government
Setting: Outpatient (any)
Synopsis
The CHANCE trial was a Chinese study that found improved outcomes with no increase in bleeding risk for patients with minor ischemic stroke or TIA given aspirin plus clopidogrel for 3 weeks. This current study broadens the population to include non-Chinese patients, uses a higher loading dose of clopidogrel (600 mg instead of 300 mg), and continues the combined clopidogrel plus aspirin for 90 days. The investigators identified patients with either a minor stroke (National Institutes of Health Stroke Scale score of 1 - 3 points) or high-risk TIA (ABCD2 score of at least 4 points) and randomized them to receive either aspirin alone or a 600-mg loading dose of clopidogrel, then 75 mg clopidogrel daily plus aspirin. The aspirin dose varied by site from 50 mg to 325 mg per day based on physician preference, but the recommended dose was 162 mg daily for 5 days, followed by 81 mg daily. All patients were recruited within 12 hours of the onset of symptoms. The primary outcome was a composite of ischemic stroke, myocardial infarction, or vascular death, and the secondary outcome was recurrent ischemic stroke within 90 days. A total of 4881 patients were recruited and randomized, but the trial was stopped early because it reached a prespecified level of increased intracranial hemorrhage. Rates of loss to follow-up were similar between groups (between 6% and 7%) and more than one-quarter of patients in each group stopped taking the study medication prematurely. The mean age of participants was 65 years, 45% were women, 20% were black; 43% had a TIA, and 57% had a minor stroke. At the end of the 90-day study period, there was no difference in the likelihood of vascular death, myocardial infarction, or all-cause mortality between groups. Although the composite outcome was less common with clopidogrel, this was due to a reduction in ischemic stroke only. Patients who received both clopidogrel and aspirin were less likely to have an ischemic stroke (4.6% vs 6.3%; P = .01; number needed to treat [NNT] = 59), but were more likely to experience a major hemorrhage (0.9% vs 0.4%; P = .01; NNT = 200); most of the difference in the latter outcome was due to noncerebral hemorrhages. The excess strokes in the aspirin-only group largely occurred in the first week, while hemorrhagic events occurred throughout the study period.
Reviewer
Mark H. Ebell, MD, MS
Professor
University of Georgia
Athens, GA
Comments
Interesting and useful information.
Good to see a government funded study that may support a change in practice in Emergency Department prior to neurology follow up
The authors in for that using clopidogre and aspirin together for the first week could be beneficial. This is a huge leap as the study did not actually examine what happens when you add clopidogrel to ASA for one week and then stop it.
Contradicts previous studies which suggested one agent or another but not both.
The good news is a reduced probability of Tia. The bad news is increased probability of hemorrhagic event or events. Study was curtailed particularly with reference to this
good
Clinically relevant.
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