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Ticagrelor/aspirin reduces stroke risk in patients with ipsilateral cervicocranial plaque

Presented by
Prof. Pierre Amarenco, Paris University, France
AHA 2020
In patients with a transient ischaemic attack (TIA) or a minor acute ischaemic stroke with ipsilateral stenosis of the cervicocranial vasculature, the P2Y12 inhibitor ticagrelor added to aspirin reduced the risk of recurrent stroke within 30 days by 27% in the THALES trial [1].

Among patients with a TIA or minor ischaemic strokes, ipsilateral atherosclerotic stenosis of cervicocranial vasculature entails the highest risk of recurrent vascular events, explained first author Prof. Pierre Amarenco (Paris University, France) [2]. Ticagrelor monotherapy was not superior to aspirin in the SOCRATES trial [3]. However, in the subgroup of patients with ipsilateral atherosclerotic stenosis, ticagrelor was superior to aspirin [4].

The THALES trial (NCT03354429) randomised 11,016 patients to ticagrelor (180 mg loading dose on day 1 followed by 90 mg twice daily for days 2–30) or placebo added to aspirin (300–325 mg on day 1 followed by 75–100 mg daily for days 2–30). Previously published results showed that ticagrelor added to aspirin was superior to aspirin alone for the prevention of stroke or death (5.5% vs 6.6%; HR 0.83; P=0.015) [5]. Prof. Amarenco presented results of a prespecified subgroup of the THALES, including 2,351 (21.3%) patients with ipsilateral, potentially causal atherosclerotic stenosis with ≥30% of cervicocranial vasculature.

The primary endpoint, time to stroke or death within 30 days, occurred in 92 of 1,136 (8.1%) patients in the ticagrelor group versus 132 of 1,215 (10.9%) in the placebo group (HR 0.73; 95% CI 0.56–0.96; P=0.023). In patients without ipsilateral stenosis, the corresponding event rate was 211 of 4,387 (4.8%) and 230 of 4,278 (5.3%), respectively (HR 0.89; 95% CI 0.74–1.08; P=0.23, Pinteraction=0.245); see Figure. In patients with ipsilateral atherosclerotic stenosis, severe bleeding (GUSTO definition) occurred in 4 (0.4%) in participants on ticagrelor and 3 (0.2%) participants on placebo, respectively. In patients without ipsilateral atherosclerotic stenosis (n=8,665) severe bleeding occurred in 24 (0.5%) and 4 (0.1%) participants, respectively (HR 5.87; 95% CI 2.04–16.90, P=0.001).

Figure: 30-day absolute event rate of stroke or death in THALES

Prof. Amarenco concluded that in patients with ipsilateral atherosclerotic stenosis, 30-day absolute event rate of stroke or death was higher (10.9% on aspirin alone) and absolute risk reduction was greater on ticagrelor added to aspirin (3.0%) than in patients with no ipsilateral stenosis (5.3% and 0.5%, respectively). He added that these findings are concordant with prior studies, suggesting that atherosclerotic disease carries a greater risk than other stroke subtypes without stenosis among patients with TIA or minor ischaemic stroke events on aspirin. “Given both the SOCRATES and THALES results, targeting patients with atherosclerotic stenosis for dual therapy with ticagrelor and aspirin could yield a clinically meaningful relative and absolute risk reduction of stroke and death as compared with aspirin alone with a number needed to treat of 34 (95% CI 19–171) and a number needed to harm of 951.”


    1. Amarenco P, et al. Ticagrelor Added to Aspirin in Acute Ischemic Stroke or Tia of Atherosclerotic Origin. LBS.03, AHA Scientific Sessions 2020, 13–17 Nov.

    2. Amarenco P, et al. N Engl J Med 2016;374:1533–1534.

    3. Johnston SC, et al. N Engl J Med. 2016;375:35–43.

    4. Amarenco P, et al. Lancet Neurol. 2017;16:301–310.

    5. Johnston SC, et al. N Engl J Med. 2020;383:207–217.


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