P2Y12i combined with aspirin superior to aspirin in patients with ipsilateral atherosclerotic stenosis
Ticagrelor added to Aspirin in Acute Ischemic Stroke or TIA of atherosclerotic Origin (THALES)
Presented at the AHA Scientific Sessions 2020 by Pierre Amarenco (Paris, France)
Introduction and methods
Of patients who suffered an transient ischemic attack (TIA) or minor ischemic stroke, those with ipsilateral atherosclerotic stenosis of cervicocranial vasculature have the highest risk of a recurrent vascular event. In the SOCRATES trial, a trial that involved 13,199 patients with an acute stroke or TIA, the potent P2Y12 inhibitor ticagrelor was not superior to aspirin. However, in a substudy of SOCRATES, ticagrelor was superior to aspirin in patients with an ipsilateral atherosclerotic stenosis compared to patients without an ipsilateral stenosis.
In the THALES trial, ticagrelor combined with aspirin was superior to aspirin alone for the outcomes stroke or death, in patients who experienced a TIA or minor stroke (HR 0.83, 95%CI: 0.71-0.96). This subanalysis of the THALES trial assessed the efficacy and safety of ticagrelor plus aspirin in patients with ipsilateral atherosclerotic stenosis of extra- or intracranial arteries.
In the THALES trial, patients (n=11,016; ≥40 years) with an acute mild ischemic stroke (NIHSS ≤5) or high-risk TIA defined as ABCD² ≥6 or symptomatic arterial stenosis ≥50% were randomized within 24 hours to 180 mg ticagrelor and 300-325 mg aspirin or placebo and 300-325mg aspirin. The patients’ medication dose was adjusted the next day to 90 mg ticagrelor twice a day plus 70-85 mg aspirin or placebo plus 70-85 mg aspirin for the remaining 30 days.
In the substudy, 2351 patients with ipsilateral stenosis were included. The primary endpoint was stroke and death. Secondary endpoints were ischemic stroke, and disabling stroke or death. Safety was assessed by bleeding events according to the GUSTO classification.
- After 30 days, the primary end point stroke and death occurred in 7.9% of patients on ticagrelor and aspirin compared to 10.9% of patients on placebo (HR 0.73, 95% CI: 0.56-0.96, P=0.023). The NNT to prevent one primary event was 34.
- The event rate among non-ipsilateral stenosis patients (n=8665) treated with ticagrelor and aspirin or aspirin alone was 4.8% vs. 5.3%, respectively (HR 0.89, 95% CI: 0.74-1.08). There was no interaction though, for presence of ipsilateral stenosis on treatment effect (Pinteraction=0.245).
- Patients treated with ticagrelor and aspirin had significantly less ischemic stroke events compared to patients treated with a placebo (HR 0.72, 95%CI: 0.55-0.95, P=0.020). Also, disabling stroke or death occurred less in the ticagrelor plus aspirin group (HR 0.72, 95%CI: 0.53-0.98, P=0.038).
- Severe bleeding events only occurred in 0.4% of patients treated with the combination ticagrelor and aspirin, compared to 0.2% in those only treated with aspirin. The number of patients needed to harm was 951.
The combination of ticagrelor and aspirin therapy resulted in a significant reduction in 30-day risk of stroke and death compared to aspirin monotherapy in high-risk ipsilateral atherosclerotic stenosis patients.
Louise D. McCullough (Houston, TX, USA), the discussant, said that it was clear from the overall THALES trial and other trials (CHANCE trial and POINT trial administrating clopidogrel), that dual antiplatelet therapy for secondary prevention in minor stroke or TIA patients, especially starting within 24 hours and continuing for the remaining 30 days, has a positive effect on stroke and mortality outcome. This substudy of THALES shows that the risk reduction was even larger in high risk patients with ipsilateral carotid stenosis.
There are still a few questions, McCullough said. There is, for sure, added value to patients with atherosclerosis, but would this dual therapy be better than carotid revascularization early after a non-disabling stroke or TIA? Furthermore, is the ticagrelor regimen better than a regimen with clopidogrel? And what treatment should be given after 30 days?
- Our reporting is based on the information during AHA Scientific Sessions 2020 -