KEY THALES SECONDARY EFFICACY END POINT

In patients with acute ischemic stroke (NIHSS ≤5) or high-risk TIA, BRILINTA provided superior risk reduction of subsequent ischemic stroke vs aspirin alone1

THALES secondary efficacy end point: Subsequent ischemic stroke at 30 days

THALES Ischemic
THALES Ischemic

IPSILATERAL ATHEROSCLEROTIC STENOSIS SUBGROUP

In patients with acute ischemic stroke (NIHSS ≤5) or high-risk TIA, BRILINTA + aspirin vs aspirin alone4

  • 21.3% of patients in the overall THALES trial (2351/11,016) had ipsilateral stenosis (≥30%) of the cervicocranial vasculature*

THALES PRESPECIFIED EXPLORATORY SUBGROUP: Primary composite end point of stroke or death in patients with ipsilateral atherosclerotic stenosis ≥30% at 30 days

K-M curves showing reduction in CV events in the prespecified exploratory subgroup of patients with ipsilateral stenosis for BRILINTA plus aspirin vs aspirin alone at 30 days in THALES.
K-M curves showing reduction in CV events in the prespecified exploratory subgroup of patients with ipsilateral stenosis for BRILINTA plus aspirin vs aspirin alone at 30 days in THALES.
  • In patients without ipsilateral stenosis: Composite of stroke or all-cause death at 30 days: 4.8% vs 5.3% with BRILINTA plus aspirin (N=4387) and aspirin alone (N=4278), respectively (HR 0.89; 95% CI 0.74–1.08; NNT for patients without ipsilateral atherosclerosis is 200)
  • BRILINTA is not indicated to reduce death in patients with acute ischemic stroke or high-risk TIA

*Included patients with symptomatic intracranial or extracranial arterial stenosis, that is, ≥30% narrowing in the diameter of the lumen of an artery that could account for the clinical presentation (irrespective of >4 mm thick aortic arch plaque). Thirty percent narrowing was chosen as cutoff based on criteria of the atherosclerosis, small vessel disease, cardiac pathology, other disease, dissection (ASCOD) grading system.

 

NNT was calculated using 1/ARR of BRILINTA + aspirin compared to aspirin alone (0.5%).4

 

THALES was not designed or powered to demonstrate the efficacy or safety of BRILINTA compared with placebo in specific subgroups. Subgroup analyses were performed to evaluate consistency of results in different cohorts. Analyses must be interpreted cautiously, as differences can reflect the play of chance among a large number of analyses.

 

SUBSEQUENT DISABLING STROKE PRESPECIFIED ANALYSIS5

In patients with acute ischemic stroke (NIHSS ≤5) or high-risk TIA

THALES prespecified exploratory analysis: Disability associated with a subsequent stroke by varying mRS threshold5*

Patients with Recurrent Stroke Events
Patients with Recurrent Stroke Events

*mRS=modified Rankin Scale. Scores range from 0 to 6 (0-1=no disability; 2-5=increasing disability; 6=death).

 

THALES was not designed or powered to demonstrate the efficacy or safety of BRILINTA compared with placebo in exploratory analyses. Exploratory analyses were performed to evaluate consistency of results in different cohorts. Analyses must be interpreted cautiously, as differences can reflect the play of chance among a large number of analyses.1

SUBSEQUENT DISABLING STROKE PRESPECIFIED ANALYSIS5

In patients with acute ischemic stroke (NIHSS ≤5) or high-risk TIA, Total disability burden at 30 days in patients with a subsequent ischemic stroke

THALES prespecified exploratory analysis: mRS distribution at 30 days in patients with a subsequent ischemic stroke5*

*mRS-modified Rankin Scale. Scores range from 0 to 6 (0-1=no disability; 2-5=increasing disability; 6=death).

 

THALES was not designed or powered to demonstrate the efficacy or safety of BRILINTA compared with placebo in exploratory analyses. Exploratory analyses were performed to evaluate consistency of results in different cohorts. Analyses must be interpreted cautiously, as differences can reflect the play of chance among a large number of analyses.1

EXPLORE MORE

THALES STUDY DESIGN

THALES was a randomized, international, double-blind, placebo-controlled, multicenter study to investigate dual antiplatelet therapy with BRILINTA (180-mg loading dose, 90 mg twice daily thereafter) and aspirin vs placebo and aspirin in the prevention of stroke or death in patients with acute ischemic stroke or transient ischemic attack (N=11,016). The primary end point was the first occurrence of the composite of stroke or death at 30 days. In both arms, patients received a loading dose of aspirin 300-325 mg followed by aspirin 75-100 mg once daily. Patients were ≥40 years of age, had mild-to-moderate acute noncardioembolic ischemic stroke (NIHSS score ≤5), or high-risk TIA (ABCD2 score ≥6 or symptomatic intracranial or extracranial arterial stenosis [≥50% narrowing in the diameter of the lumen of an artery that could account for the TIA]). Patients were randomized within 24 hours and treated for a median of 31 days.1,2

ABCD2=Age, Blood pressure, Clinical features, Duration of TIA, and Diabetes mellitus; ARR=absolute risk reduction; CI=confidence interval; HR=hazard ratio; K-M=Kaplan-Meier; mRS=modified Rankin Scale; NIHSS=National Institutes of Health Stroke Scale; NNT=number needed to treat; RRR=relative risk reduction; THALES=Acute STroke or Transient IscHemic Attack Treated with TicAgreLor and Aspirin for PrEvention of Stroke and Death; TIA=transient ischemic attack.

References
  1. Johnston SC, Amarenco P, Denison H, et al; for the THALES Investigators. Ticagrelor and aspirin or aspirin alone in acute ischemic stroke or TIA. N Engl J Med. 2020;383(3):207-217 and Supplementary Appendix.
  2. BRILINTA® (ticagrelor) [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2021.
  3. Data on file, REF-51076, AstraZeneca Pharmaceuticals LP.
  4. Amarenco P, Denison H, Evans SR, et al. Ticagrelor added to aspirin in acute nonsevere ischemic stroke or transient ischemic attack of atherosclerotic origin. Stroke. 2020;51(12):3504-3513.
  5. Amarenco P, Denison H, Evans SR, et al; for the THALES Steering Committee and Investigators. Ticagrelor added to aspirin in acute ischemic stroke or transient ischemic attack in prevention of disabling stroke: a randomized clinical trial. JAMA Neurol. 2020;78(2):1-9.