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
Brilique 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: EU label population
From PEGASUS-TIMI 54 to the EU Label: Refining the patient population
The PEGASUS trial included patients who were at between one and three years post MI. The licence for the 60mg dose of ticagrelor states that patients must be within 2 years post MI or within 12 months of P2Y12 inhibitor withdrawal.
Therefore, the EMA proposed that AstraZeneca conduct a post-hoc analysis of the patient population within the PEGASUS trial that met our licensed indication. This data is the “EU label analysis”.
a BRILIQUE 60mg and placebo groups
EMA, European Medicines Agency
Time from index MI
The benefit of BRILIQUE (ticagrelor) 60mg twice daily appeared more marked if treatment was started <2 years after the index MI28
HR and cumulative rates (KM estimate) of the primary endpoint and TIMI major bleeding with BRILIQUE vs placebo by time to index MI in PEGASUS-TIMI-54 (prespecified subgroup analysis). Adapted from reference 28.
P2Y12 inhibitor withdrawal
The benefit of BRILIQUE vs placebo was more marked in patients continuing on or restarting P2Y12 inhibitor treatment after a short interruption30
Primary efficacy endpoint
Adapted from Bonaca MP et al. 2016 and Bonaca MP et al. 2016 (supplementary information).
HR and cumulative rates (KM estimate) of the primary endpoint with BRILIQUE vs placebo by time from P2Y12 inhibitor withdrawal at randomisation in PEGASUS-TIMI-54 (prespecified subgroup analysis). P-value for interaction pooled across both doses is <0.001.
Bleeding risk was higher with BRILIQUE 60mg vs placebo
- TIMI major bleeding, interruption ≤30 days: HR=3.3, p=0.0001; >30 days and ≤1 year: HR=2.94, p=0.0002; >1 year: HR=2.1, p=0.037
PEGASUS-TIMI 54 study: EU Label subgroup summary
The risk benefit profile of Brilique (ticagrelor) 60mg vs placebo in the EU label is consistent with the overrall PEGASUS TIMI 54 population.15,32
Summary of efficacy and safety outcomes with BRILIQUE and placebo in the overall and EU label populations from PEGASUS-TIMI 54.
CV death, MI, stroke and all cause morality were secondary endpoints in the statistical analysis plan. CV death failed to meet statistical significance (p=0.07). All cause morality also failed to meet statistical significance (p=0.14), MI and stroke are therefore exploratory endpoints.
a p values should be considered exploratory and of nominal significance.
b Only the primary endpoint was statistically significant; all other endpoints should be considered exploratory.
There are limited data on the efficacy and safety of BRILIQUE 60 mg beyond 3 years of extended treatment.