Additional results from the THALES trial have shown that 1 month’s dual antiplatelet therapy with ticagrelor (Brilinta; Astra Zeneca) plus aspirin is associated with a reduction in disabling stroke, compared with aspirin alone in patients with minor stroke or high-risk transient ischemic attack (TIA).
Dr. S. Claiborne Johnston
Primary results of the THALES trial, published earlier this year in the New England Journal of Medicine, showed a reduction in the primary endpoint of stroke or death within 30 days with the combination of ticagrelor plus aspirin versus aspirin alone, although this was accompanied by an increase in bleeding. In terms of risk/benefit, the main results showed that for every 1,000 patients treatment with ticagrelor on top of aspirin would prevent 11 strokes or deaths at the cost of four severe hemorrhages.
The current exploratory analysis, which focuses on the severity of the strokes occurring in the trial, was published online Nov. 7 in JAMA Neurology to coincide with its presentation at the European Stroke Organisation-World Stroke Organization Conference 2020.
Results showed that, compared with aspirin alone, ticagrelor plus aspirin significantly reduced the 30-day risk for disabling stroke or death (4.0% versus 4.7%), and the total disability burden (the shift analysis of the distribution of modified Rankin scale) following subsequent ischemic stroke was reduced by a significant 23%.
“This new information on disabling stroke underlines the importance of getting patients on dual antiplatelet therapy quickly after a TIA or mild stroke,” said principal investigator of the THALES trial, S. Claiborne Johnston, MD, PhD.
Dr. Johnston, who is dean of Dell Medical School at the University of Texas at Austin, added: “It’s reassuring that ticagrelor has this effect, which was pretty robust. An accompanying editorial to the THALES publication in the NEJM incorrectly stated that ticagrelor did not reduce risk of disabling stroke, so it is good to be able to correct that misconception with this new data.”
Lead author of the exploratory analysis, Pierre Amarenco, MD, professor of neurology at Bichat University Hospital, Paris, added: “The main results showed that ticagrelor on top of aspirin reduced stroke but now we have new information showing reduction in disabling stroke. Obviously, these are the most important types of stroke to prevent. These are the strokes that will impact patients functionally.”
The THALES trial included 11,016 patients with a noncardioembolic, nonsevere ischemic stroke (National Institutes of Health Stroke Scale [NIHSS] score ≤ 5) or high-risk TIA, of whom 10,803 had modified Rankin Scale (mRS) functional score recorded at 30 days.
They were randomized within 24 hours of symptom onset to ticagrelor (180-mg loading dose on day 1 followed by 90 mg twice daily for 1 month) or placebo. All patients received aspirin (300-325 mg on day 1 followed by 75-100 mg daily for 1 month).
In the new analysis, time to occurrence of disabling stroke (mRS greater than 1) or death within 30 days occurred in 221 of 5,511 patients (4.0%) randomized to ticagrelor and in 260 of 5,478 patients (4.7%) randomized to placebo (hazard ratio, 0.83; P = .04).
The ordinal analysis of mRS in patients with recurrent stroke showed a shift of the disability burden following a recurrent ischemic stroke in favor of ticagrelor (odds ratio, 0.77; P = .002).
Factors associated with disability were baseline NIHSS score of 4-5, ipsilateral stenosis of at least 30%, Asian race/ethnicity, older age, and higher systolic blood pressure.
Asked how the current results compared with observations reported in the main NEJM paper of similar incidences of disability (mRS > 1) in the two groups, Dr. Johnston explained that the result in the original paper looked at disability in the overall population, not just those who went on to have a stroke during follow-up.
“The problem with looking at overall disability is that most of it is actually from the index stroke (the one that led to the patient being enrolled in the trial). That creates a lot of noise that overwhelms the benefit in reducing disability due to new stroke, the thing we really care about and the subject of the new paper,” he commented.