#VisualAbstract: Ticagrelor and aspirin vs. aspirin alone for ischemic stroke or TIA

1. Ticagrelor and aspirin taken after a mild-to-moderate acute non-cardioembolic stroke or high-risk transient ischemic attack led to a lower rate of subsequent stroke within 30 days.

2. The incidence of overall disability at 30 days did not differ between groups.

Evidence Rating Level: 1 (Excellent)

Study Rundown: Following an acute ischemic stroke or transient ischemic attack (TIA), the risk of a subsequent ischemic stroke is estimated to be 5-10% within the first few months. A number of trials have sought to examine the role of antiplatelet agents to mitigate such a risk. Ticagrelor is a P2Y-12 inhibitor increasingly employed as part of dual antiplatelet therapy (DAPT) following myocardial infarction and coronary reperfusion. Evidence from prior subgroup analyses has suggested its potential benefit when used in combination with aspirin after an ischemic stroke. This multi-center, placebo-controlled, randomized controlled trial found use of aspirin and ticagrelor following a mild-moderate acute non-cardioembolic stroke or TIA to reduce the composite risk of stroke or death within thirty days when compared with use of aspirin alone. Such a finding provides further evidence in support of a short-term role of DAPT therapy following acute stroke, demonstrating a magnitude of benefit similarly exhibited in previous studies examining DAPT therapy within this setting. However, caution must be exercised in interpreting the study’s principal finding. The report of a reduced rate of stroke or death, while both included in the pre-defined primary outcome, fails to qualify the nearly equivalent all-cause mortality rate observed at thirty days in both groups. Differences in the presented primary outcome are explained largely by the reduced rate of ischemic stroke at 30 days. It should be noted there was no incident reduction in disability at 30 days between groups and a higher rate of severe bleeding – including rates of intracranial hemorrhage or fatal bleeding – was observed in those taking both aspirin and ticagrelor. The study may benefit from further characterization of functional outcomes to better delineate the risk, benefit profile.

Click here to read the study, published today in NEJM

Relevant Reading: Antiplatelet Therapy in Ischemic Stroke and Transient Ischemic Attack: An Overview of Major Trials and Meta-Analysis

In-Depth [randomized controlled trial]: A total of 11,016 patients were enrolled and underwent randomization across 414 sites in twenty-eight countries from January 2018 until October 2019. Patients were eligible if they were found to have a mild-to-moderate acute noncardioembolic ischemic stroke or a high-risk TIA and were not planned for an endovascular intervention, including thrombectomy or thrombolysis. Randomization occurred within twenty-four hours of symptom onset or last known normal. Subjects were loaded and maintained on either aspirin and ticagrelor or aspirin and placebo for at least thirty days, after which antiplatelet therapy was left to the discretion of study site investigators. Follow-up data was collected at approximately five, thirty, and sixty days following randomization.  The primary-outcome event rate, defined as a composite risk of stroke or death within 30 days of follow-up, was lower in those taking aspirin and ticagrelor (5.5%) when compared to those taking aspirin alone (6.6%), (HR 0.83, 95% CI 0.71-0.96). The rate of ischemic stroke was lower in those taking aspirin and ticagrelor group (5.0% vs 6.3%, HR 0.79, 95% CI 0.68-0.93). No significant difference was seen in the rate of death (HR 1.33, 95% CI 0.81-2.19) or overall disability at 30 days (OR 0.98, 95% CI 0.89-1.07). A higher rate of severe bleeding was seen in 0.5% of those in the ticagrelor group, compared to 0.1% in those taking placebo (HR 3.99, 95% CI 1.74-9.14). Permanent discontinuation due to bleeding or dyspnea occurred in 3.8% of those in the aspirin and ticagrelor group, compared to 0.8% in those taking aspirin alone.

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