Dual antiplatelet treatment with clopidogrel and aspirin may be beneficial for stroke reduction in the first 2 weeks after a minor stroke or transient ischemic attack (TIA). However, the risk of bleeding may outweigh the benefits after day 10, according to a post-hoc analysis of the Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events (CHANCE) trial, published in Neurology.
Based on the results of the CHANCE trial, the American Heart Association/American Stroke Association recommends clopidogrel and aspirin for 21 days starting in the first 24 hours after a minor stroke or TIA. However, the 21-day duration was arbitrary, according to the study investigators. “The risk of bleeding increased as the duration of dual antiplatelet therapy became prolonged,” they wrote.
Yuesong Pan, MD, of Beijing Tiantan Hospital in China, and colleagues analyzed data from the CHANCE trial to evaluate the short-term risks and benefits of clopidogrel and aspirin in patients with minor ischemic stroke or TIA.
The CHANCE trial was a randomized double-blind controlled trial that included 5170 patients to assess the efficacy and safety of clopidogrel plus aspirin (n=2584) compared with aspirin alone (n=2586) in minor stroke and TIA. The investigators defined acute minor stroke as a National Institutes of Health (NIH) Stroke Scale of ≤3 and a high risk TIA as an ABCD2 score of 4 or more.
New ischemic strokes occurred in 204 patients in the clopidogrel-aspirin group, with 71.1% (n=145) occurring in the first week, 6.4% (n=13) in the second week, and 5.9% (n=12) in the third week. In the aspirin-only group, there were 295 new ischemic strokes, with 75.6% (n=223) occurring in the first week, 6.4% (n=19) in the second week, and 2.7% (n=8) in the third week.
Bleeding occurred in 60 patients in the clopidogrel-aspirin group, with 38.3% (n=23) occurring in the first week, 25% (n=15) in the second week, and 15% (n=9) in the third week. Bleeding occurred in 41 patients in the aspirin-only group, with 36.6% (n=15) occurring in the first week, 19.5% (n=8) in the second week, and 7.3% (n=3) in the third week.
The investigators noted that combination treatment with clopidogrel and aspirin reduced the risk of an ischemic stroke within the first 2 weeks; however, the risk of bleeding outweighed the benefit from day 10 on.
“Antiplatelet therapy was a double-edged sword: high platelet inhibition decreased the risk of recurrent ischemic events but increased the risk of bleeding,” they wrote.
Limitations of the study included the small sample size and the fact that the study only enrolled Chinese patients; the results would need to be validated in a larger sample and with non-Asian participants.
“This time course analysis showed that clopidogrel-aspirin treatment may have a benefit of reducing ischemic stroke risk outweighing the potential risk of increased bleeding primarily within the first 2 weeks compared with aspirin alone in patients with minor ischemic stroke or TIA,” the researchers concluded.
Pan Y, Jing J, Chen W, et al. Risks and benefits of clopidogrel-aspirin in minor stroke or TIA: Time course analysis of CHANCE [published online April 19, 2017]. Neurology. doi:10.1212/WNL.0000000000003941