THALES: Ticagrelor plus aspirin reduces 30-day recurrent stroke, death vs. aspirin alone
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Ticagrelor plus aspirin lowered the risk for stroke or death within 30 days compared with placebo in patients with acute ischemic stroke or transient ischemic attack who did not undergo IV or endovascular thrombolysis, researchers found.
Both groups had a similar incidence of disability, according to the THALES trial published in The New England Journal of Medicine.
“Although there was an increased risk for bleeding, the absolute risk was small compared with the benefit in reducing strokes,” S. Claiborne Johnston, MD, dean of the Dell Medical School at the University of Texas at Austin and lead investigator for the THALES trial, told Healio.
In this randomized trial, researchers analyzed data from 11,016 patients aged at least 40 years with mild to moderate acute noncardioembolic ischemic stroke or TIA without thrombolysis or thrombectomy.
“The rates of stroke in these patients are simply too high, even with aspirin, the prior standard of care,” Johnston said in an interview. “Ticagrelor had promising characteristics as an antiplatelet agent, and we hoped that it would benefit patients when used with aspirin.”
Within 24 hours of symptom onset, patients were assigned ticagrelor (Brilinta, AstraZeneca) plus aspirin (n = 5,523; mean age, 65 years; 38% women) or matching placebo plus aspirin (n = 5,493; mean age, 65 years; 40% women), both of which were given for 30 days. Patients assigned combination therapy received loading doses of ticagrelor (180 mg then 90 mg twice per day) and aspirin (300 mg to 325 mg on the first day then 75 mg to 100 mg daily).
The primary outcome was a composite of stroke or death at 30 days. Secondary outcomes included first subsequent ischemic stroke and disability within 30 days. A primary safety outcome was defined as severe bleeding.
Stroke or death occurred in 5.5% of patients assigned ticagrelor plus aspirin compared with 6.6% of those assigned aspirin alone (HR = 0.83; 95% CI, 0.71-0.96).
Ischemic stroke occurred in 5% of patients in the ticagrelor plus aspirin group vs. 6.3% of those in the aspirin alone group (HR = 0.79; 95% CI, 0.68-0.93). The incidence of disability was not significantly different in patients assigned ticagrelor plus aspirin (23.8%) compared with those assigned aspirin alone (24.1%; OR = 0.98; 95% CI, 0.89-1.07).
Severe bleeding was observed in 0.5% of patients assigned ticagrelor plus aspirin vs. 0.1% of those assigned aspirin alone (P = .001).
“We have another proven treatment to reduce stroke risk in these high-risk patients,” Johnston told Healio.
For more information:
S. Claiborne Johnston, MD, can be reached at clay.johnston@austin.utexas.edu.
Perspective
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Larry B. Goldstein, MD, FAAN, FANA, FAHA
Previous studies including POINT (Johnston SC, et al. N Engl J Med. 2018;doi:10.1056/nejmoa1800410) and CHANCE (Wang Y, et al. N Engl J Med. 2013;doi:10.1056/NEJMoa1215340) showed that a short course of clopidogrel plus aspirin was superior to aspirin alone in preventing major vascular events (mainly stroke) in patients with an acute minor ischemic stroke or TIA. Clopidogrel is a prodrug that requires hepatic conversion for activation, but an estimated 25% to 30% of white people and 50% to 60% of Asian people have genetic variants that affect conversion to the active agent. Ticagrelor is similar to clopidogrel but does not require metabolic activation.
Despite differences in patient populations, endpoints and treatment regimens, the results are similar to those of POINT and CHANCE supporting the benefit that a short course of dual antiplatelet therapy reduces major vascular events during the high-risk period after ischemic stroke or TIA. This comes at a cost of a small but significant increase in bleeding complications. There was no effect of the combination of ticagrelor and aspirin in reducing disability compared with aspirin alone.
These findings support a short course of DAPT.
Comparisons between clopidogrel plus aspirin vs. ticagrelor plus aspirin vs. aspirin alone are only indirect. A direct head-to-head comparison would be helpful to determine whether one combination offers benefit compared with the other.
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