Ticagrelor + aspirin benefit most for patients with artery plaque

Adding ticagrelor to aspirin significantly reduces the risk of stroke and death compared with aspirin alone in patients with plaque build-up in their arteries known as ipsilateral atherosclerotic stenosis — thus highlighting the patient subgroup most likely to benefit from the combination therapy, based on a prespecified analysis of the THALES* study.

Among patients with ipsilateral atherosclerotic stenosis (n=2,351), the primary outcome of stroke or death within 30 days occurred at significantly lower rates in those treated with ticagrelor plus aspirin compared with aspirin alone, both on a background of standard care (7.9 percent vs 10.9 percent, hazard ratio [HR], 0.73; p=0.023). [AHA 2020, session LBS.07; Stroke 2020;doi:10.1161/STROKEAHA.120.032239]

On the other hand, there was no significant difference between the two treatment arms among patients without ipsilateral stenosis (n=8,665; 4.8 percent vs 5.3 percent; HR, 0.89; p=0.23).

Previously, the primary analysis of THALES has shown that adding ticagrelor to aspirin significantly reduced the risk of stroke or death at 30 day by 17 percent compared with aspirin in the overall cohort with acute ischaemic stroke or transient ischaemic attack (TIA) — with the difference mainly driven by driven by a lower rate of ischaemic stroke.

“Among patients with ischaemic stroke, 40 percent present with ipsilateral stenosis of the cervicocranial vasculature and have the highest risk of recurrence among ischaemic stroke aetiologic subtypes,” the researchers explained.

In the current prespecified analysis, the investigators therefore zoomed in on the role of ipsilateral atherosclerotic stenosis of cervicocranial vasculature in the treatment effect.

“This is 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 event on aspirin,” said lead investigator Professor Amarenco of Bichat Hospital in Paris, France, who presented the findings during the AHA 2020 Congress.

“The risk in the atherosclerotic group was double the risk of those without atherosclerotic disease,” he reported.

While the interaction between ipsilateral stenosis and treatment effect was not significant (p-interaction=0.245), the investigators noted that the combination therapy yielded a clinically meaningful risk reduction in the primary outcome, with a number needed to treat of 34.

Unlike the main trial which found increased bleeding risk with the combination therapy in the overall population, the current subanalysis showed no significant increase in the rates of severe bleeding between the combination arm and the aspirin arm (0.4 percent vs 0.2 percent; p=non-significant) among patients with ipsilateral stenosis.

The corresponding rates for severe bleeding in those without ipsilateral stenosis were 0.5 percent and 0.1 percent, respectively (HR, 5.87; p=0.001).

Select patients to benefit

The findings on prevention of stroke and death were also in line with the SOCRATES trials, which showed similar benefits of adding ticagrelor on the patient subgroup with ipsilateral atherosclerosis, and a significant interaction effect.

“These patients form indisputably a group to target with this therapy after a TIA or a minor ischaemic stroke … may guide treating physicians to a patient population with potentially larger treatment effect,” highlighted Amarenco and co-authors.

“This population is nowadays easily identifiable in clinical practice since imaging of extracranial and intracranial arteries is recommended upon arrival in stroke unit using computed tomography angiography, magnetic resonance angiography, or ultrasonography,” they pointed out.

*THALES: The acute stroke or Transient iscHemic Attack treated with ticagreLor and aspirin for prEvention of Stroke and death trial