A subgroup analysis of the THALES trial showed that ticagrelor added to aspirin reduced the 30-day risk of recurrent stroke by 27% in transient ischemic attack (TIA) and minor ischemic stroke patients with ipsilateral atherosclerotic stenosis of cervicocranial vasculature.
The findings were presented Monday by lead author Pierre Amarenco, MD, of Bichat Hospital, Paris, in a late-breaking session at the American Heart Association (AHA) Scientific Sessions 2020 virtual conference, and the study was simultaneously published in AHA’s Stroke journal.
The 40% of TIA and minor ischemic stroke patients who have ipsilateral atherosclerotic stenosis of cervicocranial vasculature have the highest risk of recurrent vascular events among ischemic stroke etiologic subtypes, Amarenco and colleagues note.
There have been previous efficacy signals for the same ticagrelor-plus-aspirin regimen in these patients in the failed SOCRATES study. Although the clinical trial did not meet its primary endpoint overall of proving ticagrelor’s superiority versus aspirin, it was found that the newer blood thinner did result in a 32% relative risk reduction in recurrent stroke and cardiovascular events compared with aspirin among the ipsilateral atherosclerotic stenosis of cervicocranial vasculature subgroup.
This was considered “hypothesis generating,” the researchers said.
The 11,016-patient randomized, placebo-controlled, double-blind THALES trial also studied ticagrelor and aspirin – this time successfully demonstrating a reduction of stroke and death by 17%. At the Scientific Sessions on Monday, Amarenco presented a subgroup analysis of the 2,351 patients in the study who had ipsilateral atherosclerotic stenosis. This subgroup was randomized to aspirin plus either ticagrelor in a 180 mg loading dose on day 1 (within 24 hours of onset), followed by 90 mg twice daily until day 30, or placebo.
Although the researchers found no interaction between the overall study population and the ipsilateral atherosclerosis stenosis subgroup, they did identify both a higher absolute risk and a greater 30-day risk reduction of stroke or death in the subgroup.
For the ipsilateral atherosclerotic stenosis group, the risk of another stroke or death dropped by 27% on the full regimen compared with the placebo combination.
After 30 days, stroke or death had occurred in 92 (8.1%) of the 1,136 subgroup patients randomized to receive the study drug combination, versus 132 (10.9%) of the 1,215 in the cohort given aspirin alone (hazard ratio [HR], 0.73; 95% confidence interval [CI], 0.56 – 0.96: p=0.023), with a number needed to treat of 34 (95% CI, 19-171).
In the patients without ipsilateral stenosis, the corresponding event rate was 211 (4.8%) out of 4,387 on study drug versus 230 (5.4%) out of 4,278 on placebo (HR, 0.89; 95% CI, 0.74–1.08; p=0.23, p for interaction =0.245).
Severe bleeding occurred in four (0.4%) of the patients given ticagrelor compared to three (0.2%) on placebo in the ipsilateral atherosclerotic stenosis subgroup, and in 24 (0.5%) and four (0.1%), respectively, in those without ipsilateral stenosis (HR, 5.87; 95% CI, 2.04-16.9: p=0.001).
Absolute risk reduction was greater for patients with ipsilateral atherosclerotic stenosis given ticagrelor added to aspirin (3%) than for patients with no ipsilateral stenosis (0.5%), Amarenco pointed out during his presentation.
“In this easily identified population ticagrelor added to aspirin provided a clinically meaningful benefit with a number needed to treat of 34,” the researchers said.
“These patients form indisputably a group to target with this therapy after a TIA or a minor ischemic stroke.”
In an accompanying press statement, Amarenco – a professor of neurology at Paris University – urged health care professionals to now consider both ticagrelor and aspirin to prevent another stroke in patients who experience a warning stroke.
“Our research shows treating patients within 24 hours of their first symptoms using this newer regimen is effective, especially when the cause of the stroke is due to plaque build-up in the arteries,” he said.
Amarenco was joined by Texas Medical Center’s Louise McCullough, MD, during a news conference announcing the results. McCullough asked whether the risk for “very high risk patients” could be reduced through more screening for atherosclerosis.
She raised other questions, such as whether the benefit could also be greater than carotid revascularization early after the TIA or non-disabling stroke and what the result could mean for tissue-type plasminogen activator (tPA) treated patients (who were excluded).
In any case, she said, “it certainly seems that ticagrelor plus aspirin could be a very good choice” for those with atherosclerosis, “just like clopidogrel may be a good choice in patients with peripheral vascular disease”.
McCullough had no disclosures, although the study authors list links with a host of pharma companies including AstraZeneca, the manufacturer or ticagrelor.