Clay Johnston, MD, PhDClay Johnston, MD, PhD
AstraZeneca announced that phase 3 THALES trial of ticagrelor (Brilinta) in the treatment of stroke met its primary end point, reducing the risk of the composite of stroke and death after an acute ischemic stroke (AIS) or transient ischemic attack (TIA).1

The drug previously received FDA approval for lowering the risk of heart attack, or death from heart attack or stroke in patients with acute coronary syndrome (ACS) in September 2018. At the time, the drug was approved in 60 mg and 90 mg doses. In the PEGASUS-TIMI 54 trial, ticagrelor reduced the risk of cardiovascular death in patients by 29%.

“The risk of having a subsequent stroke is highest in the first few days and weeks after a minor acute ischemic stroke or high-risk transient ischemic attack. While an expected increase in bleeding was observed, the findings from THALES showed that Brilintain combination with aspirin, reduced the risk of potentially devastating events in this crucial time," Clay Johnston, lead investigator for the THALES trial and dean of the Dell Medical School at the University of Texas at Austin, said in a statement.

AstraZeneca also announced plans to announce the full results of the trial at a forthcoming medical meeting.

The double-blind, placebo-controlled, randomized phase 3 trial (NCT03354429) examined ticagrelor, an oral, reversible, direct-acting P2Y12 receptor antagonist, pairing it with aspirin in 11,000 patients who had a minor AIS or TIA in the 24 hours prior to treatment initiation. On day 1, patients received 180 mg of ticagrelor followed by 90-mg doses twice daily on days 2 through 30, or matching placebo. At treatment initiation, patients received 300 to 325 mg of aspirin, followed by a 75 to 1000-mg dose once daily between days 2 through 30.  

Time to the composite end point of stroke and death at 30 days was the primary efficacy outcome of the trial. The investigators used a severe bleeding event, defined by the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO), as a primary safety endpoint.

Patients reached clinically meaningful reduction in the risk of primary composite endpoint of stroke and death, compared to aspirin alone. Investigators noted the preliminary findings of ticagrelor were consistent with previous profile.

Previoulsy, tricagrelor’s benefit over aspirin in preventing stroke was assessed in the SOCRATES trial, but it failed to achieve statistical significance. In SOCRATES (NCT01994720), there were 6589 patients treated with the therapy, of which 6.7% (n = 442) experienced a primary end point event of stroke, myocardial infarction, or death within 90 days. The aspirin group experienced an end point event at a rate of 7.5% (n = 49), comparatively, for a hazard ratio of 0.89 (95% CI, 0.78–1.01; P = .07). Major bleeding occurred in 0.5% of patients treated with ticagrelor and in 0.6% of patients treated with aspirin, intracranial hemorrhage in 0.2% and 0.3%, respectively, and fatal bleeding in 0.1% and 0.1%.2
REFERENCE
1. Brilinta met primary endpoints in the phase 3 THALES trial in stroke [news release]. Camridge, UK: AstraZeneca; Published January 27, 2020. finance.yahoo.com/news/brilinta-met-primary-endpoint-phase-120000766.html. Accessed January 27, 2020.
2. Johnston SC, Amarenco P, Albers GW, et al. Ticagrelor versus Aspirin in Acute Stroke or Transient Ischemic Attack. N Engl J Med. 2016; 375:35-43. doi: 10.1056/NEJMoa1603060.