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)

PEGASUS-TIMI 54 study

Long-term treatment with BRILIQUE (ticagrelor) 60 mg reduces the risk of a further CV event vs placebo

In the PEGASUS-TIMI 54, BRILIQUE (ticagrelor) 60 mg twice daily significantly reduced the rate of CV death, MI, or stroke (primary endpoint) over 3 years vs placebo.15

BRILIQUE 60mg significantly reduced CV events vs placebo: 7.77 vs. 9.04% (p=0.004)
BRILIQUE 60mg significantly reduced CV events vs placebo: 7.77 vs. 9.04% (p=0.004)

95 % CI: 0.74-0.95. Adapted from Bonaca et al 2015

Risk of CV death, MI, or stroke (KM estimate) with BRILIQUE (ticagrelor) and placebo in patients who had an index MI 1-3 years before randomisation. All patients were on background low-dose asprin (75-150 mg/day). 

The effect of BRILIQUE (ticagrelor) 60 mg twice daily was directionally consistent on all components of the primary endpoint15

Contributions to the composite primary endpoint
Contributions to the composite primary endpoint

Adapted from Bonaca et al 2015

HR and cumulative rates (KM estimate) for the primary endpoint and each of its components in patients treated with BRILIQUE (ticagrelor) and placebo.

a secondary endpoint. b Exploratory endpoint.
CI confidence interval
ARR absolute risk reduction
RRR relative risk reduction
HR hazard ratio
KM Kaplan-Meier
 

PEGASUS-TIMI 54 bleeding rates

BRILIQUE (ticagrelor) 60 mg twice daily is associated with an increased risk of TIMI major and minor bleeding vs placebo.

In PEGASUS-TIMI 54, TIMI major and minor bleedings were more frequent with BRILIQUE vs placebo15

  • There were no significant differences in the rates of  fatal bleeding or non-fatal ICH (Intracranial haemorrhage)

Bleeding events leading to treatment discontinuation were more frequent with BRILIQUE (6.2% vs 1.5%, p<0.001)15

  • These occurred early during treatment and were mostly non-major27
Bleeding rates for BRILIQUE 60mg compared with placebo
Bleeding rates for BRILIQUE 60mg compared with placebo

Bleeding rates (KM estimate) with BRILIQUE (ticagrelor) and placebo in PEGASUS-TIMI54. All patients were on background low-dose asprin (75-150 mg/day).15

TIMI, Thrombolysis in Myocardial Infarction
ICH, intracranial haemorrhage

Discontinuation of treatment due to bleeding was more common with BRILIQUE (ticagrelor) 60mg twice daily compared with ASA therapy alone (6.2% and 1.5%, respectively; p<0.001). The majority of these bleedings were of less severity (classified as TIMI requiring medical attention), e.g. epistaxis, bruising and haematomas.1

PEGASUS-TIMI 54 study: bleeding definitions28

Major bleed:

  1. Any intracranial bleeding, OR
  2. Clinically overt signs of haemorrhage associated with a drop in haemoglobin (Hgb) of ≥5 g/dL  (or, when haemoglobin is not available, a fall in haematocrit of ≥15%), OR
  3. Fatal bleeding (a bleeding event that directly led to death within 7 days)

Minor bleed:

  • Any clinically overt sign of haemorrhage (including imaging) that is associated with a fall in Hgb of 3 to <5g/dL (or, when haemoglobin is not available, a fall in haematocrit of 9 to <15%)
  • Transfusions were accounted for by adjusting Hgb measurements for any packed red blood cells (PRBCs) or whole blood given between baseline and post-transfusion measurements. A transfusion of one unit of blood was assumed to result in an increase of 1gm/dL in Hgb

Medical attention:

Any overt sign of haemorrhage that meets one of the following criteria and that does not meet criteria for a major or minor bleeding event

  • Requiring intervention: defined as medical practitioner-guided medical or surgical treatment to stop or treat bleeding including temporarily or permanently discontinuing or changing the dose of a medication or study drug
  • Leading to hospitalisation: defined as leading to or prolonging hospitalisation
  • Prompting evaluation: defined as leading to unscheduled contact with a healthcare professional and diagnostic testing (laboratory or imaging)

Minimal bleed: Any overt bleeding event that does not meet the preceding criteria

*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)

Study design

PEGASUS-TIMI 54 is the first prospective, randomised, controlled clinical trial robustly powered to assess the benefit of long-term dual anti-platelet therapy in post-MI patients at high risk* of atherothrombotic events.15

 

 

The PEGASUS-TIMI 54 study included a high risk population15
High risk patients in the Brilique (ticagrelor) 60mg indication
High risk patients in the Brilique (ticagrelor) 60mg indication

a  Estimated creatinine clearance <60 mL/min.
b  Based on an interim snapshot of the data, after completion of enrollment but during ongoing trial and data cleaning9

Randomisation and study treatment

PEGASUS-TIMI 54 was a randomised, double-blind, placebo-controlled clinical trial.15

Patient were randomised 1:1:1 to BRILIQUE (two different doses) and placebo, plus low-dose aspirin
Patient were randomised 1:1:1 to BRILIQUE (two different doses) and placebo, plus low-dose aspirin

*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

There are limited data on the efficacy and safety of BRILIQUE (ticagrelor) 60mg beyond 3 years of extended treatment

There are limited data on the efficacy and safety of BRILIQUE 60mg beyond 3 years of extended treatment