Bleeding in the THEMIS trial

In high-risk patients with CAD who had T2D and no history of MI or stroke,

  • Primary Safety End Point (TIMI Major bleeding) BRILINTA 60 mg plus aspirin (N=9562) vs aspirin alone (N=9531):
    • K-M% at 36 months, 2.2% vs 1.0%, respectively (HR 2.32; 95% CI 1.82-2.94)1
    • Events per 1000 patient years: 9 vs 4, respectively2
  • Fatal bleeding events per 1000 patient years: 1 vs 0, respectively2
 

Bleeding in patients with and without history of PCI3*

Bleeding in patients with and without history of PCI3*

 

 

 


TIMI major bleeding


TIMI major or minor bleeding


Fatal bleeding


Intracranial hemorrhage

PATIENTS WITH HISTORY OF PCI

BRILINTA 60 mg + aspirin (N=5536)

Aspirin (N=5564)

n (%) patients with events

TIMI major bleeding111 (2.0%)

TIMI major or minor bleeding157 (2.8%)

Fatal bleeding6 (0.1%)

Intracranial hemorrhage33 (0.6%)

PATIENTS WITH HISTORY OF PCI

Aspirin (N=5564)

n (%) patients with events

TIMI major bleeding62 (1.1%)

TIMI major or minor bleeding80 (1.4%)

Fatal bleeding6 (0.1%)

Intracranial hemorrhage31 (0.6%)

 

 

 


TIMI major bleeding


TIMI major or minor bleeding


Fatal bleeding


Intracranial hemorrhage

PATIENTS WITHOUT HISTORY OF PCI

BRILINTA 60 mg + aspirin (N=4026)

Aspirin (N=3967)

n (%) patients with events

TIMI major bleeding95 (2.4%)

TIMI major or minor bleeding128 (3.2%)

Fatal bleeding11 (0.3%)

Intracranial hemorrhage37 (0.9%)

PATIENTS WITHOUT HISTORY OF PCI

Aspirin (N=3967)

n (%) patients with events

TIMI major bleeding38 (1.0%)

TIMI major or minor bleeding49 (1.2%)

Fatal bleeding4 (0.1%)

Intracranial hemorrhage15 (0.4%)

THEMIS used the following bleeding severity categorization: TIMI major: fatal bleeding or any intracranial bleeding or clinically overt signs of hemorrhage associated with a drop in Hb of ≥5 g/dL or a fall in Hct of ≥15%. Fatal: a bleeding event that directly led to death within 7 days. TIMI minor: clinically apparent with 3-5 g/dL decrease in Hb.

 

*Safety analysis population was all randomly assigned patients who took at least 1 dose of study drug.3

 

THEMIS 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.

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THEMIS STUDY DESIGN

THEMIS was a randomized, double-blind, placebo-controlled trial of ticagrelor vs placebo in 19,220 patients, on top of low-dose (75 to 150 mg) aspirin for the prevention of thrombotic CV events (CV death, MI, stroke). Patients ≥50 years with type 2 diabetes receiving an anti-hyperglycemic medication for at least 6 months, and with stable CAD (ie, history of PCI, CABG, or angiographic stenosis ≥50% in at least 1 coronary artery) were enrolled. Patients with known prior MI or stroke were excluded. Patients were treated for a median of 33 months and up to 58 months.1,2

CABG=coronary artery bypass graft; CAD=coronary artery disease; CV=cardiovascular; Hb=hemoglobin; Hct=hematocrit; MI=myocardial infarction; PCI=percutaneous coronary intervention; THEMIS=Effect of Ticagrelor on Health Outcomes in DiabEtes Mellitus Patients Intervention Study; TIMI=Thrombolysis in Myocardial Infarction; T2D=type 2 diabetes.

References
  1. Steg PG, Bhatt DL, Simon T, et al; for the THEMIS Steering Committee and Investigators. Ticagrelor in patients with stable coronary disease and diabetes. N Engl J Med. 2019;381(14):1309-1320.
  2. BRILINTA® (ticagrelor) [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2021.
  3. Bhatt DL, Steg PG, Mehta SR et al; for the THEMIS Steering Committee and Investigators. Ticagrelor in patients with diabetes and stable coronary artery disease with a history of previous percutaneous coronary intervention (THEMIS-PCI): a phase 3, placebo-controlled, randomised trial. Lancet. 2019;394(10204):1169-1180.