Benefit/Risk of Ticagrelor-Aspirin vs. Aspirin After Acute Ischemic Stroke or TIA
- In this post hoc analysis of a trial of mono vs. dual antiplatelet therapy continued for 30 days post-stroke/TIA, the number needed to treat to prevent a major ischemic event in the aspirin and ticagrelor group compared to the aspirin and placebo group was 84.
- The number needed to harm to cause a major hemorrhagic event in the aspirin and ticagrelor group compared to the aspirin and placebo group was 345.
- If 1,000 patients are treated with ticagrelor and aspirin instead of aspirin alone for 30 days after nonsevere stroke/TIA, a reduction in 12 major ischemic events and an increase in three major hemorrhagic events would be expected.
What is the absolute risk reduction (ARR) of major ischemic events versus the absolute risk increase (ARI) of major hemorrhagic events in patients treated with ticagrelor and aspirin as compared to placebo and aspirin for 30 days after acute nonsevere ischemic stroke or high-risk transient ischemic attack (TIA)?
This is a post hoc analysis of THALES, a multinational double-blinded trial published in 2020. Eligible patients were ≥40 years old and had a nonsevere (National Institutes of Health Stroke Scale [NIHSS] score ≤5) noncardioembolic ischemic stroke or high-risk TIA and were randomized within 24 hours of last known normal. Patients were treated for 30 days with either ticagrelor (loading dose 180 mg followed by 90 mg twice daily) plus aspirin (loading dose 300 or 325 mg followed by a dose of 75-100 mg daily) versus placebo plus aspirin. The primary efficacy outcome was major ischemic events, defined as the composite of ischemic stroke and nonhemorrhagic death. The primary safety outcome was major hemorrhagic events, defined as the composite of intracranial hemorrhage and hemorrhagic death.
The ARR of major ischemic events in the ticagrelor and aspirin group compared to the placebo and aspirin group was 1.19% (95% confidence interval [CI] for risk difference, 0.31-2.07) for a number needed to treat of 84. The ARI of major hemorrhagic events in the ticagrelor and aspirin group compared to the placebo and aspirin group was 0.29% (95% CI for risk difference, 0.10-0.48) for a number needed to harm of 345. The ARR remained greater than the ARI even when restricting the analysis to events producing any disability or to events producing moderate-to-severe disability.
If 1,000 patients are treated with ticagrelor and aspirin instead of aspirin alone for 30 days after nonsevere stroke/TIA, a reduction in 12 major ischemic events and an increase in three major hemorrhagic events would be expected.
The primary endpoint in the original THALES analysis, chosen with encouragement from regulatory authorities, was a composite of ischemic stroke, hemorrhagic stroke, and all-cause death in a time-to-event analysis. The primary endpoint was met by 5.5% of patients in the ticagrelor and aspirin group and by 6.6% of patients in the aspirin group (hazard ratio, 0.83; 95% CI, 0.71-0.96) by 30 days. Because this primary endpoint contained both efficacy (e.g., lower ischemic stroke incidence) and safety (e.g., higher hemorrhagic stroke incidence) components, a direct comparison of benefits and harms between the two groups was difficult.
This is a post hoc analysis of THALES performed by the original study authors using discrete ischemic versus hemorrhagic endpoints. These data more readily demonstrate the drivers of the favorable benefit-risk profile of ticagrelor and aspirin as compared to placebo and aspirin taken for 30 days after nonsevere ischemic stroke or high-risk TIA.
Keywords: Aspirin, Brain Ischemia, Hemorrhage, Hemorrhagic Stroke, Intracranial Hemorrhages, Ischemic Attack, Transient, Ischemic Stroke, Numbers Needed To Treat, Secondary Prevention, Stroke, Ticagrelor, Vascular Diseases
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