Acute Ischemic Stroke and High-Risk TIA

Combination antiplatelet therapy with clopidogrel and aspirin may reduce the rate of recurrent stroke during the first 3 months after a minor ischemic stroke or transient ischemic attack (TIA). A trial of combination antiplatelet therapy in a Chinese population has shown a reduction in the risk of recurrent stroke. We tested this combination in an international population.

A total of 4881 patients were enrolled at 269 international sites. The trial was halted after 84% of the anticipated number of patients had been enrolled because the data and safety monitoring board had determined that the combination of clopidogrel and aspirin was associated with both a lower risk of major ischemic events and a higher risk of major hemorrhage than aspirin alone at 90 days. Major ischemic events occurred in 121 of 2432 patients receiving clopidogrel plus aspirin and in 160 of 2449 patients receiving aspirin plus a placebo, with most events occurring during the first week after the initial event. Major hemorrhage occurred in 23 patients receiving clopidogrel plus aspirin and 10 patients receiving aspirin plus placebo.

In summary, patients with minor ischemic stroke or high-risk TIA, those who received a combination of clopidogrel and aspirin had a lower risk of major ischemic events but a higher risk of major hemorrhage at 90 days than those who received aspirin alone.

My Take:
The accompanying editorial points out that most of the benefit of this combination therapy is during the first week following a minor stroke or TIA. Limiting the use of both drugs to three weeks was recommended.

The use of aspirin as secondary prevention (after an ischemic event) is well established as a medical standard. However, the common practice of taking an aspirin daily as primary prevention is not. Several studies have demonstrated that the side effects of daily aspirin, including major hemorrhage and death, exceed any benefit in preventing an initial event. Again, the odds favor the use of aspirin after a patient has suffered a heart attack, stroke, or TIA.

The Bottom Line:
If you are taking an aspirin daily, even a low-dose or “baby” aspirin for primary prevention, please review this practice with your primary care physician. It is not the standard of care. If you have had a vascular event and are taking a daily aspirin with another blood thinner (combination therapy), like this study, please review this practice with your health care provider. Although still an accepted practice, the long term risks involved outweigh the benefits.

Source: May 16, 2018 New England Journal of Medicine