Bleeding in the THALES trial

In patients with acute ischemic stroke (NIHSS ≤5) or high-risk TIA, Primary safety end point: GUSTO* severe bleeding event1,2

 


GUSTO severe bleeding

GUSTO severe bleeding

BRILINTA 90 mg + aspirin (N=5523) K-M%, n

K-M% n (0.5%) 280.5% 28

Placebo + aspirin (N=5493) K-M%, n

K-M% n(0.1%) 7 0.1% 7

AT 30 DAYS

AT 30 DAYSHR: 3.99 95% CI: 1.74-9.14 ARI: 0.4% NNH 2632

  • Intracranial bleeding and fatal bleeding seen in THALES for BRILINTA + aspirin vs aspirin alone, respectively2:

       

    • ICH: 21 vs 6
    •  

    • Fatal bleeding: 11 vs 2
  •  

* GUSTO severe bleeding: Any one of the following: fatal bleeding, intracranial bleeding (excluding asymptomatic hemorrhagic transformations of ischemic brain infarctions and excluding microhemorrhages <10 mm evident only on gradient-echo magnetic resonance imaging), bleeding that caused hemodynamic compromise requiring intervention (eg, systolic blood pressure <90 mm Hg that required blood or fluid replacement, or vasopressor/inotropic support, or surgical intervention).2

IPSILATERAL ATHEROSCLEROTIC STENOSIS SUBGROUP

In patients with acute ischemic stroke (NIHSS ≤5) or high-risk TIA, Bleeding outcomes in patients with and without ipsilateral stenosis3

Patients with ipsilateral stenosis ≥30%

 

 


GUSTO severe bleeding


Fatal bleeding


ICH


Hemorrhagic stroke

BRILINTA 90 mg + Aspirin (N=1136)

Aspirin (N=1215)

No. of patients (%)

GUSTO severe bleeding4 (0.4%)

Fatal bleeding1 (0.1%)

ICH4 (0.4%)

Hemorrhagic stroke0 (0.0%)

Aspirin (N=1215)

No. of patients (%)

GUSTO severe bleeding3 (0.2%)

Fatal bleeding1 (0.1%)

ICH3 (0.2%)

Hemorrhagic stroke0 (0.0%)

Patients without ipsilateral stenosis ≥30%

 

 


GUSTO severe bleeding


Fatal bleeding


ICH


Hemorrhagic stroke

BRILINTA 90 mg + Aspirin (N=4387)

Aspirin (N=4278)

No. of patients (%)

GUSTO severe bleeding24 (0.5%)

Fatal bleeding10 (0.2%)

ICH16 (0.4%)

Hemorrhagic stroke10 (0.2%)

Aspirin (N=4278)

No. of patients (%)

GUSTO severe bleeding4 (0.1%)

Fatal bleeding1 (0.0%)

ICH3 (0.1%)

Hemorrhagic stroke2 (0.0%)

– NNH for patients without ipsilateral atherosclerosis is 2503*

 

* GUSTO severe bleeding: Any one of the following: fatal bleeding, intracranial bleeding (excluding asymptomatic hemorrhagic transformations of ischemic brain infarctions and excluding microhemorrhages <10 mm evident only on gradient-echo magnetic resonance imaging), bleeding that caused hemodynamic compromise requiring intervention (eg, systolic blood pressure <90 mm Hg that required blood or fluid replacement, or vasopressor/inotropic support, or surgical intervention).2

FROM THE PRESPECIFIED IPSILATERAL ATHEROSCLEROSIS SUBGROUP ANALYSIS

Every 34 Patients with Ipsilateral Atherosclerosis
For every 34 patients with ipsilateral atherosclerosis (≥30%) treated with BRILINTA 90 mg plus aspirin instead of aspirin, 1 additional event of stroke or death was prevented...
Every 951 Patients with Ipsilateral Atherosclerosis
...and for every 951 patients with ipsilateral atherosclerosis (≥30%), 1 additional GUSTO severe bleeding event occurred.3,4†

*NNH was calculated using 1/ARI of BRILINTA + aspirin compared to aspirin alone (0.4%).3

Calculation of NNH is based off of 1/ARI (1/[0.352%-0.247%]).3

 

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.2

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; ARI=absolute risk increase; CI=confidence interval; CV=cardiovascular; GUSTO=Global Use of Strategies to Open Occluded Coronary Arteries; HR=hazard ratio; ICH=intracranial hemorrhage; K-M=Kaplan-Meier; NIHSS=National Institutes of Health Stroke Scale; NNH=number needed to harm; THALES=Acute STroke or Transient IscHemic Attack Treated with TicAgreLor and Aspirin for PrEvention of Stroke and Death; TIA=transient ischemic attack.

References
  1. BRILINTA® (ticagrelor) [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2021.
  2. 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.
  3. 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.
  4. Data on file, REF-51076, AstraZeneca Pharmaceuticals LP.