BRILIQUE® (ticagrelor)

BRILIQUE (ticagrelor) is the only P2Y12 inhibitor licensed in combination with aspirin to protect patients with prior MI and a high risk* of atherothrombotic events against subsequent CV events in both the acute and long-term treatment settings†1

*High risk is defined as ≥1 additional atherothrombotic risk factor (age ≥65 years, >1 prior MI, multivessel coronary artery disease, diabetes requiring medication, chronic non-end-stage renal dysfunction)1

†BRILIQUE (ticagrelor) 90mg twice daily  in combination with  acetylsalicylic acid (ASA) is indicated for patients with Acute Coronary Syndromes (ACS) for up to 12 months. BRILIQUE (ticagrelor) 90mg twice daily is not indicated for use in patients beyond 12 months. There are limited data on the efficacy and safety of BRILIQUE (ticagrelor) 60mg beyond 3 years of extended treatment

Clinical Studies

BRILIQUE (ticagrelor) demonstrated acute and long-term CV protection across two large studies: PLATO and PEGASUS-TIMI 54 respectively.4,15

The PLATO study compared BRILIQUE (ticagrelor) (180-mg loading dose, 90mg twice daily thereafter) and clopidogrel (300-mg to 600-mg loading dose, 75 mg daily thereafter) for the prevention of thrombotic CV events (CV death, MI, or stroke) in 18,624 patients admitted to hospital with an ACS with or without ST-segment elevation. Patients were treated for at least 6 months and up to 12 months.4

BRILIQUE (ticagrelor) – the only oral antiplatelet with evidence demonstrating a statistically and clinically significant reduction in CV mortality at 12 months compared to clopidogrel in patients with ACS.4,16

The PEGASUS-TIMI 54 study compared BRILIQUE (ticagrelor) (90 mg twice daily or 60 mg twice daily) vs. placebo, each given with low-dose aspirin, for the prevention of thrombotic CV events (CV death, MI, or stroke) in 21,162 patients ≥50 years of age with a history of MI (1 to 3 years prior to randomisation) and at high risk* of another atherothrombotic event.15

*High risk is defined as ≥1 additional atherothrombotic risk factor (age ≥65 years, >1 prior MI, multivessel coronary artery disease, diabetes requiring medication, chronic non-end-stage renal dysfunction)

PLATO

BRILIQUE (ticagrelor) 90mg significantly reduced CV events vs. clopidogrel4

Briligue (ticagrelor) 90 mg twice daily with low dose ASA (75-100mg daily) demonstrated a significant reduction in the risk of CV events compared to clopidogrel with ASA in ACS patients.

Time to first occurrence of primary efficacy endpoint: Composite of death from vascular causes, MI or stroke at 12 months4

Primary efficacy endpoint: CV death, MI or stroke at 12 months
Primary efficacy endpoint: CV death, MI or stroke at 12 months

No. at Risk

  Month 0 Month 2
 Month 4
 Month 6
 Month 8
 Month 10
 Month 12
Ticagrelor 9333 8628 8460 8219 6743 5161 4147
Clopidogrel 9291 8521 8362 8124 6650 5096 4047

Analysis at 30 days is an exploratory endpoint

Risk (KM estimate) of CV death, non-fatal MI or non-fatal stroke (primary endpoint) in patients with ACS treated with Brilique (ticagrelor) over 12 months. All patients were on background low-dose asprin (75-100 md/day). Adapted from Wallentin et al. 2009

More than half of the absolute risk reduction with BRILIQUE (ticagrelor) occurred after 30 days treatment, and continued to diverge from that of clopidogrel over 12 months of continuous therapy.4

BRILIQUE (ticagrelor) 90mg significantly reduced CV mortality vs. clopidogrel4

Briligue (ticagrelor) 90 mg twice daily with low dose ASA (75-100mg daily) significantly reduced the risk of death from vascular causes alone vs. clopidogrel with ASA4

Secondary efficacy endpoint: Death from vascular causes alone at 12 months4

Secondary efficacy endpoint CV mortality at 12 months
Secondary efficacy endpoint CV mortality at 12 months

Adapted from Wallentin et al 2009

No. at Risk

  Month 0 Month 2
 Month 4
 Month 6
 Month 8
 Month 10
 Month 12
Ticagrelor 9333 8924 8822 8626 7119 5482 4419
Clopidogrel 9291 8865 8780 8589 7079 5441 4364

PLATO bleeding rates

There was no significant difference in total major and fatal bleeding despite improved efficacy vs. clopidogrel4

Non-CABG related major bleeding was higher with BRILIQUE (ticagrelor) than with clopidogrel (PLATO criteria: 4.5% vs 3.8%, p=0.03)4

In PLATO4, there was no increase in either PLATO defined or TIMI defined major bleeding with ticagrelor vs clopidogrel (PLATO major bleeding: HR 1.04, P=0.43; TIMI major bleeding: HR 1.03, P=0.57). There was also no increase in fatal bleeding (HR 0.87, P=0.66) or intracranial bleeding (HR 1.87, P=0.06). However, there was an increase in fatal intracranial bleeding (ticagrelor 11/9235 (0.1%), clopidogrel 1/9186 (0.01%), P=0.02). Non-CABG related major bleeding was increased (PLATO definition: HR 1.19, P=0.03; TIMI definition: HR 1.25, P=0.03). PLATO minor & minimal bleeding were also increased in patients treated with ticagrelor vs clopidogrel: PLATO minor bleeding 4.8% vs 3.8%; PLATO minimal bleeding 17.2% vs clopidogrel 10.6%44.

 

Bleeding definitions in the PLATO study

  PLATO4 TIMI15
Major

Life-threatening

  • Fatal, intracranial or pericardial with tamponade
  • Hypovolaemic shock or severe hypotension requiring pressors or surgery
  • Decrease in haemoglobin >5 g/dL or transfusions of ≥4 units for bleeding

Other

  • Significantly disabling (e.g. intraocular)
  • Decrease in haemoglobin of 3–5 g/dL or transfusion of 2–3 units for bleeding
  • Clinically overt (including imaging) bleeding or documented symptomatic intracranial haemorrhage
  • Decrease in haemoglobin ≥5 g/dL
Minor
  • Requires medical intervention to treat or stop bleeding
  • Clinically overt (including imaging) bleeding
  • Decrease in haemoglobin ≥3 and <5 g/dL
Minimal
  • All other bleeding events not requiring intervention or treatment
  • Clinically overt (including imaging) bleeding
  • Decrease in haemoglobin <3 g/dL

Primary (PLATO-defined major bleeding) and secondary safety endpoints4

PLATO Bleeding Rates
PLATO Bleeding Rates

* Secondary safety endpoints of the trial

a  Fatal intracranial bleeding occurred in 0.1% (11/9,235) patients in the BRILIQUE (ticagrelor) group and 0.01% (1/9186) patients in the clopidogrel group (p=0.02).24

Study design

The PLATO study was a large, multicentre, double-blind, randomised trial.4

Patient were randomised 1:1 to either BRILIUQE 90mg or clopidogrel, plus low-dose ASA
Patient were randomised 1:1 to either BRILIUQE 90mg or clopidogrel, plus low-dose ASA

aSTEMI patients for primary PCI were randomised, however, they may not have received PCI
bA loading dose of 300mg clopidogrel was permitted in patients not previously treated with clopidogrel, with an additional 300mg allowed at the discretion of the investigator
cThe PLATO study expanded the definition of major bleeding to be more inclusive compared with previous studies in ACS patients.

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