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

 

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)

APOLLO HELICON/HESIOD

Study results

Following an MI, your patients remain at high risk of further CV events for up to 5 years

  • National registry data from Sweden (n=97,254) and Denmark (n=55,747) have shown that ~1 in 5 patients surviving an acute MI experience further CV events during the first year post-discharge17,18
  • Of patients who are event-free at 1 year, up to another 1 in 5 experience an event in the following 3–4 years17,18
Apollo study risk
Apollo study risk

Cumulative risk of MI, ischaemic stroke or CV death during the first year after the index MI and in the subsequent 3 years in the Swedish population. Adapted from reference 17.

CV, cardiovascular; MI, myocardial infarction

Large-scale, real-world retrospective analyses of Swedish and Danish national registry data evaluating CV risk in patients surviving an acute MI during the first year post-event and in subsequent years.17,18

  Sweden (n=97,254) Denmark (n=55,747)
Data Sources

National Inpatient Register

Swedish Prescribed Drug Register

Cause of Death Register

Civil Registrations System

Danish National Patient Registry

Danish Register of Causes of Death

Danish Heart Registry

Danish National Registry of Medicinal Product Statistics

Integrated Database for Labour Market Research

Inclusion criteria

MI population (index MI until day 365) Patients admitted to hospital with a primary diagnosis of acute MI between 01/07/2006 and 30/06/2011, who  were discharged with a diagnosis of acute MI and were alive 7 days after discharge.

Stable post-MI population (day 366 until study end) Patients who survived the first 365 days after the index MI, without a stroke or recurrent MI.

MI population (day 7 after hospital discharge until the primary endpoint, death, emigration or day 365 after discharge)

Patients aged ≥18 years with first recorded primary or secondary diagnosis of index MI between 01/01/2004 and 31/12/2010 and no prior MI admissions in the previous 12 months, who survived the index MI without a stroke or recurrent MI within 7 days of discharge.

Stable post-MI population (day 366 after hospital discharge until the primary endpoint, death, emigration or study end)

Patients who survived the first 365 days after the index MI, without a stroke or recurrent MI.

Exclusion criteria
Patients who died within 7 days of discharge following the index MI.
Patients who died, or had recurrent MI or stroke, within 7 days of discharge and those with a recent MI history (≤12 months before the index event).
Primary endpoint
Composite endpoint of non-fatal MI, non-fatal stroke or CV death.
Composite endpoint of non-fatal MI, non-fatal stroke or CV death.
Mean follow-up
2.5 years 3.6 years

The risk your patients face may be higher than observed in clinical trials

  • UK electronic health record data (CALIBER) are consistent with the findings from Sweden and Denmark
    • 17.2% of patients surviving an acute MI for ≥1 year had further events over the following 3 years
       
  • In high-risk patients matching the inclusion and exclusion criteria of the PEGASUS-TIMI 54 the risk of further CV events was 18.8%19
    • This compares with a recurrent CV event rate of 9.0% in the placebo arm of the clinical trial15,a
APOLLO CALIBER
APOLLO CALIBER

Cumulative CV risk in the overall population, in high-risk patients matching the PEGASUS-TIMI 54 inclusion and exclusion criteria, and in the placebo arm of the trial. Adapted from references 15 and 19

a  Bleeding (fatal, severe or intracranial) risk was 2.3% in the overall study population and 3.0% in PEGASUS - patientlike, vs 1.06% in the PEGASUS-TIMI 54 placebo arm (TIMI major bleeding).

Comparison of baseline demographics in the CALIBER and PEGASUS-TIMI 54 populations

CALIBER population
CALIBER population

Key baseline characteristics of the CALIBRE and PEGASUS-TIMI 54 populations. Adapted from references 15 and 19.

a Information was available for 94% of patients.
b Multivessel disease was not coded in the CALIBER registry, but it was identified as an important risk factor for further CV events in the Danish registry study.18
c Information was available for 88% of patients.
eGFR, estimated glomerular filtration rate; NA, not available; NSTEMI, non-ST-elevation myocardial infarction;
PCI, percutaneous coronary intervention; STEMI, ST-elevation myocardial infarction.

Study design19

Observational cohort study based on the CALIBER platform with linked electronic health records across primary care (CPRD), ACS registry (MINAP), hospital care (hospital episodes statistics), and cause-specific mortality (Office for National Statistics).

The study included patients admitted to hospital with a primary diagnosis of ACS between April 2005 and March 2010, who survived for at least 1 year after the index MI (n=7,328). A subpopulation of high-risk patients who met the PEGASUS-TIMI 54 trial inclusion (age ≥65,or ≥50 with diabetes, renal disease or a second previous MI) and exclusion criteria was also analysed (n=1,676). Multivessel disease was not coded in the CALIBER registry.

Primary endpoints

  • Composite endpoint of non-fatal MI, non-fatal stroke or CV death
  • Fatal, severe, or intracranial bleeding

Median follow-up

  • 1.5 years

ACS, acute coronary syndrome; CPRD, Clinical Practice Research Datalink; MINAP, Myocardial Ischaemia National Audit Project.

Culprit and non-culprit recurrent ischaemic events in MI patients

The goal of secondary prevention is to reduce the risk of overall coronary disease progression, not just stent-related events22

The risk of recurrent MI is twice as high in non-culprit lesions (NCL) vs culprit lesions (CL)22

SWEDEHEART registry: cumulative proportion with identifiable lesions at recurrent MI

PRECLUDE study
PRECLUDE study

Of the 3464 recurrent MIs, 1566 were indeterminate events and could not be classified as NCL or CL recurrent MIs - because no PCI was performed for the recurrent MI or they were not treated in a SWEDEHEART unit or invasively evaluated.

Treatment with BRILIQUE (ticagrelor) 90mg twice daily is recommended for 12 months in ACS patients.

BRILIQUE (ticagrelor) 60 mg twice daily is the recommended dose when an extended treatment is required for patients with a history of MI of a least 1 year and a high risk of an atherothrombotic event. There is limited data on the efficacy and safety or ticagrelor beyond 3 years of extended treatment.

This analysis was an observational cohort study using prospectively collected data from SWEDEHEART and the Swedish National Board of Healthcare registries.

The study population consisted of 44,332 out of 108,615 patients hospitalised for STEMI or NSTEMI who had a culprit lesion identified at baseline by coronary angiography (between 1 July 2006 and 29 November 2014). During follow-up (median 3.2 years) re-MI occurred in 3,464 patients. Of those patients, the infarct originated from a ‘non-culprit’ lesion in 1,243 patients, from a ‘culprit’ lesion in 655 patients and 1,566 re-MIs could not be classified as ‘non-culprit’ or ‘culprit’.

Medications at hospital discharge for the index MI: ASA 95.8%; clopidogrel 69.6%; ticagrelor 23.5%; prasugrel 2.4%.

 

ASA, acetylsalicylic acid