Antiplatelet Therapy in Minor Ischemic Stroke or TIA

A 66-year-old woman with a history of hyperlipidemia is hospitalized for 2 days following acute dysarthria lasting 15 minutes that has since resolved. She is diagnosed with a transient ischemic attack (TIA) and is ready to be discharged. She was taking aspirin and a statin before she was admitted. What is the best antiplatelet therapy for her to prevent a recurrent TIA or stroke?

Antiplatelet therapy is a cornerstone of treatment for secondary prevention of ischemic stroke or TIA. Aspirin was the first antiplatelet agent used and remains one of the most commonly prescribed. Short-duration dual antiplatelet therapy is also used, but long-term dual antiplatelet therapy is not recommended owing to an increased risk of severe bleeding. The standard dual antiplatelet regimen includes aspirin plus clopidogrel for patients with minor ischemic stroke (NIHSS ≤3) or moderate-to-high risk TIA (ABCD score ≥4). Now, results from a recent study published in NEJM suggest that ticagrelor could be another option for dual antiplatelet therapy with aspirin.

Researchers conducted a large multicenter, randomized, placebo-controlled trial to compare ticagrelor plus aspirin versus aspirin alone in patients with acute mild-to-moderate ischemic stroke or high-risk TIA. The primary outcome of stroke or death within 30 days was lower with ticagrelor plus aspirin than with aspirin alone, however this result was accompanied by an increased incidence of bleeding in the ticagrelor group. 

Although this study provides another viable option for dual antiplatelet therapy following minor stroke or TIA, the risk of bleeding associated with ticagrelor must be balanced with the benefit of preventing recurrent TIA or stroke. As noted in an accompanying editorial, the bleeding risk associated with ticagrelor and aspirin might exceed the benefit in lower-risk patients. Therefore, in the low-risk patient described above, the risk of bleeding from adding ticagrelor outweighs the potential benefit. She should be continued on aspirin only.

The following NEJM Journal Watch summary further explains the study.

Seemant Chaturvedi, MD reviewing Johnston SC et al. N Engl J Med 2020 Jul 16

The main treatment options for acute minor stroke or transient ischemic attack (TIA) currently are aspirin (A) alone or with clopidogrel (A+C). Ticagrelor (T) reversibly binds and inhibits the P2Y12 receptor on platelets and is widely used to prevent vascular events caused by ischemic heart disease. To test A+T in patients with stroke or TIA, researchers conducted a multicenter, manufacturer-sponsored trial involving 11,016 patients (mean age, 65 years; 39% women; 77% with hypertension, 29% with diabetes), mostly from Europe and Asia. Participants had a mild stroke (NIH Stroke Scale score ≤5) or a high-risk TIA starting within 24 hours before enrollment and did not receive thrombolysis or thrombectomy or require anticoagulation. Participants were randomized to aspirin alone (300- to 325-mg loading dose, then 75–100 mg daily) or with ticagrelor (180-mg loading dose, then 90 mg twice daily). The primary outcome was stroke or death within 30 days; stroke alone was a secondary endpoint. The primary safety outcome was severe bleeding.

Most participants (91%) had a stroke rather than TIA; approximately one third were treated within 12 hours of symptom onset. The primary outcome was significantly lower with A+T than with aspirin alone (5.5% vs. 6.6%). Recurrent ischemic stroke was 21% less common with A+T than with aspirin alone, a significant difference (5.0% vs. 6.3%). Disability outcomes did not differ between the treatments. Severe bleeding was significantly more common with A+T than with aspirin alone (0.5% vs. 0.1%), including intracranial hemorrhage (0.4% vs. 0.1%).

Comment: This study provides a welcome new option for stroke prevention in patients with recent minor stroke or TIA, particularly those who are genetically poor metabolizers of clopidogrel. Overall results are somewhat similar to previous findings with aspirin plus clopidogrel. As with other antithrombotic agents, clinicians must balance the benefits of stroke prevention with an increased bleeding risk.

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Siri is a 2020-2021 NEJM Editorial Fellow. She graduated from Internal Medicine Residency at Indiana University.