#1 Prescribed OAP for STEMI PCI1

BRILINTA patient sitting on an adirondack chair, enjoying a day in the backyard
BRILINTA patient sitting on an adirondack chair, enjoying a day in the backyard

ACS—PLATO CV DEATH AND OTHER SECONDARY EFFICACY END POINTS

SUPERIORITY saves lives: BRILINTA SIGNIFICANTLY REDUCED CV DEATH vs clopidogrel at 12 months in patients with ACS2,3

PLATO secondary efficacy end point

CV death at 12 months2,3*

The PLATO Secondary End Point
The PLATO Secondary End Point
PLATO BLEEDING
PLATO PRIMARY EFFICACY
NET BENEFIT ANALYSIS
THROMBOTIC CV EVENTS OVER TIME
PLATO STUDY DESIGN

*K-M rate is the rate of first events only.

 

†Hazard ratio derived from a Cox proportional-hazards model on data from the primary and secondary end points.3

 

NNT=number needed to treat and is calculated as 1/ARR.

 

Relative risk increase is calculated by inverting the HR for CV death at 12 months (0.79), subtracting 1 from that number, and multiplying by 100.

  • Secondary efficacy end point of CV death at 12 months for BRILINTA plus aspirin vs clopidogrel plus aspirin: Events per 1000 patient years: 45 vs 57, respectively

Why choose second best?

SAVE MORE LIVES with BRILINTA

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Couple Relaxing

Additional PLATO secondary efficacy end points2,3

Patients with outcome events (events/1000 patient years)

Patients with outcome events (events/1000 patient years)

 

MIǂ§

Stroke§

All-cause mortality

BRILINTA 90 mg + aspirin (N=9333)

MIǂ§65

Stroke§16

All-cause mortality51

Clopidogrel + aspirin (N=9291)

MIǂ§76

Stroke§14

All-cause mortality65

Outcomes at 12 months (K-M%)

Outcomes at 12 months (K-M%)

 

MIǂ§

Stroke§

All-cause mortality

BRILINTA 90 mg + aspirin (N=9333)

MIǂ§5.8

Stroke§1.5

All-cause mortality4.5

Clopidogrel + aspirin (N=9291)

MIǂ§6.9

Stroke§1.3

All-cause mortality5.9

HR (95% CI)†

MIǂ§0.84 (0.75–0.95)

Stroke§1.17 (0.91–1.52)

All-cause mortality0.78 (0.69–0.89)

P-value

MIǂ§0.0045

Stroke§0.22

All-cause mortality0.0003ǁ

†Hazard ratio derived from a Cox proportional-hazards model on data from the primary and secondary end points.3

 

‡Excluding silent MI.

 

§Including patients who could have had other nonfatal events or died.

 

||Due to the hierarchical test sequence in PLATO, all-cause mortality was an exploratory analysis and, therefore, the P-value is nominal.3

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ACS—PLATO PRIMARY EFFICACY END POINT

Treat patients with ACS, not just the stent. SUPERIOR CV EVENT REDUCTION with BRILINTA vs clopidogrel at 12 months2,3

PLATO primary efficacy end point

Composite of CV death, MI,* or stroke at 12 months2,3

PLATO Primary Efficacy End Point
PLATO Primary Efficacy End Point

PLATO OUTCOMES CONFIRMED in >45,000 patients

with ACS studied in real-world registry2,5

PLATO BLEEDING
NET BENEFIT ANALYSIS
THROMBOTIC CV EVENTS OVER TIME
NSTEMI & CKD SUBGROUP ANALYSES
PLATO STUDY DESIGN

*Excluding silent MI.

 

†Hazard ratio derived from a Cox proportional-hazards model on data from the primary and secondary end points.3

 

NNT=number needed to treat and is calculated as 1/ARR.

 

     

  • Events per 1000 patient years for BRILINTA vs clopidogrel: 111 vs 131, respectively
  • BRILINTA and clopidogrel were studied with aspirin and other standard therapies3

    •  

Why choose second best?

Make SUPERIORITY with BRILINTA your choice

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PRIOR MI—PEGASUS PRIMARY EFFICACY END POINT

In patients with prior MI, BRILINTA 60 mg + aspirin had superior CV event reduction at 3 years vs aspirin in PEGASUS2,7

PEGASUS primary efficacy end point

The PEGASUS Primary Efficacy End Point
The PEGASUS Primary Efficacy End Point
PEGASUS BLEEDING
PEGASUS STUDY DESIGN
  • Events per 1000 patient years for BRILINTA 60 mg plus aspirin vs aspirin: 26 vs 31, respectively

Patients were treated for at least 12 months and up to 48 months with a median follow-up time of 33 months2

  • BRILINTA was studied in patients already on standard CV therapies in the PEGASUS trial7

*Due to rounding, the ARR is 1.27% and not 1.2%.

NNT=number needed to treat and is calculated as 1/ARR.

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PLATO STUDY DESIGN 

PLATO was a randomized, international, double-blind, controlled comparative study in patients with ACS hospitalized with or without ST-segment elevation, with an onset of symptoms within 24 hours (N=18,624). The study compared BRILINTA (180-mg loading dose, 90 mg twice daily thereafter) to clopidogrel (300-mg to 600-mg loading dose, 75 mg daily thereafter) for the prevention of thrombotic CV events (CV death, MI, or stroke). Study period was 12 months, with median duration of therapy of 277 days. BRILINTA and clopidogrel were studied with aspirin and other standard therapies.2,3

SWEDEHEART REAL-WORLD REGISTRY

An observational real-world comparative effectiveness study evaluated 45,073 consecutive patients with acute MI, discharged on clopidogrel or ticagrelor, using data from the SWEDEHEART Registry between 2010 and 2013. The analysis was adjusted for patient age, sex, pre-existing comorbidities, ACS presentation characteristics, in-hospital course, and discharge medications. This was an observational registry trial and while analyses were adjusted for confounding factors, the results are subject to potential bias and should be interpreted with caution.6

PEGASUS STUDY DESIGN

PEGASUS-TIMI 54 compared BRILINTA (90 mg twice daily or 60 mg twice daily) vs placebo, each given with low-dose aspirin (75 to 150 mg), 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 randomization). Patients also had at least 1 risk factor for thrombotic CV events (age ≥65 years, diabetes mellitus requiring medication, at least 1 other prior MI, evidence of multivessel coronary artery disease, or creatinine clearance <60 mL/min). Only the 60-mg dose strength is approved for use in patients with a history of MI 1 year after an ACS event. Patients were treated for at least 12 months and up to 48 months with a median follow-up time of 33 months.2,7

ACC=American College of Cardiology; ACS=acute coronary syndrome; AHA=American Heart Association; ARR=absolute risk reduction; CI=confidence interval; CKD=chronic kidney disease; CV=cardiovascular; HR=hazard ratio; K-M=Kaplan-Meier; MI=myocardial infarction; NNT=number needed to treat; NSTEMI=non–ST-elevation myocardial infarction; OAP=oral antiplatelet; PCI=percutaneous coronary intervention; PEGASUS=Prevention of Cardiovascular Events in Patients with Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin; PLATO=PLATelet inhibition and patient Outcomes; RRR=relative risk reduction; STEMI=ST-elevation myocardial infarction; SWEDEHEART=Swedish Web-system for Enhancement and Development of Evidence-based Care in Heart Disease Evaluated According to Recommended Therapies; TIMI=Thrombolysis in Myocardial Infarction.

References
  1. Data on File, US-65430, AstraZeneca Pharmaceuticals LP.
  2. BRILINTA® (ticagrelor) [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2024.
  3. Wallentin L, Becker RC, Budaj A, et al; PLATO Investigators. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2009;361(11):1045-1057 and Supplementary Appendix.
  4. Data on File, REF-4911, AstraZeneca Pharmaceuticals LP.
  5. Data on File, REF-51076, AstraZeneca Pharmaceuticals LP.
  6. Sahlén A, Varenhorst C, Lagerqvist B, et al. Outcomes in patients treated with ticagrelor or clopidogrel after acute myocardial infarction: experiences from SWEDEHEART registry. Eur Heart J. 2016;37(44):3335-3342.
  7. Bonaca MP, Bhatt DL, Cohen M, et al; PEGASUS-TIMI 54 Steering Committee and Investigators. Long-term use of ticagrelor in patients with prior myocardial infarction. N Engl J Med. 2015;372(19):1791-1800.
BRILINTA WAS STUDIED IN PATIENTS ALREADY ON STANDARD CV THERAPIES IN THE PEGASUS TRIAL1

PEGASUS was designed to test the hypothesis that long-term therapy with BRILINTA added to low-dose aspirin reduces the risk of thrombotic CV events among patients with a history of MI.1

PEGASUS was a randomized, double-blind, placebo-controlled clinical trial. Patients underwent randomization at 1161 sites in 31 countries. The study compared BRILINTA (90 mg twice daily or 60 mg twice daily) vs placebo, each given with low-dose aspirin (75 mg to 150 mg), 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 randomization). Patients also had at least 1 of the following risk factors for thrombotic CV events: age ≥65 years, diabetes mellitus requiring medication, at least 1 other prior MI, evidence of multivessel coronary artery disease, or creatinine clearance <60 mL/min. Patients were excluded if they required renal dialysis, had a previous intracranial hemorrhage, had gastrointestinal bleeding within 6 months, had a known bleeding diathesis or coagulation disorder, or required treatment with anticoagulants. Patients were treated for at least 12 months and up to 48 months with a median follow-up time of 33 months.1,2

  • Both BRILINTA 60-mg and 90-mg dosages were studied as part of the PEGASUS trial. Only the 60-mg dose strength is approved for use in patients with a history of an MI 1 year after an ACS event

ACS=acute coronary syndrome; CV=cardiovascular; MI=myocardial infarction; PEGASUS=Prevention of Cardiovascular Events in Patients with Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin.

References: 1. Bonaca MP, Bhatt DL, Cohen M, et al; PEGASUS-TIMI 54 Steering Committee and Investigators. Long-term use of ticagrelor in patients with prior myocardial infarction. N Engl J Med. 2015;372(19):1791-1800. 2. BRILINTA® (ticagrelor) [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2024.

BRILINTA was studied in more than 18,000 patients with ACS in PLATO1,2

BRILINTA 90 mg plus aspirin was studied vs clopidogrel plus aspirin in more than 18,000 patients, including STEMI (ST-elevation myocardial infarction), NSTEMI (non–ST-elevation myocardial infarction), and UA (unstable angina) patients, across 43 countries and 862 sites in the PLATO (PLATelet inhibition and patient Outcomes) study.1

Patients were treated for at least 6 months and up to 12 months. Patients were excluded if they had a previous intracranial hemorrhage, had gastrointestinal bleeding within 6 months, had a known bleeding diathesis or coagulation disorder, or required treatment with anticoagulants. BRILINTA and clopidogrel were studied with aspirin and other standard therapies.2

PLATO was designed to mirror real-world clinical practice across ACS diagnoses and medical or invasive treatment approaches.3

PLATO included both medical and invasive (PCI or CABG) treatment approaches. Patients who received fibrinolytic therapy within the previous 24 hours or who had a need for chronic oral anticoagulation therapy were excluded.2

ACS=acute coronary syndrome; CABG=coronary artery bypass graft; PCI=percutaneous coronary intervention; PLATO=PLATelet inhibition and patient Outcomes.

References: 1. Wallentin L, Becker RC, Budaj A, et al; PLATO Investigators. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2009;361(11):1045-1057 and Supplementary Appendix. 2. BRILINTA® (ticagrelor) [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2024. 3. James S, Åkerblom A, Cannon CP, et al. Comparison of ticagrelor, the first reversible oral P2Y12 receptor antagonist, with clopidogrel in patients with acute coronary syndromes: rationale, design, and baseline characteristics of the PLATelet inhibition and patient Outcomes (PLATO) trial. Am Heart J. 2009;157(4):599-605.

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IMPORTANT SAFETY INFORMATION FOR BRILINTA® (ticagrelor) 60-MG AND 90-MG TABLETS

WARNING: BLEEDING RISK

  • BRILINTA, like other antiplatelet agents, can cause significant, sometimes fatal bleeding
  • Do not use BRILINTA in patients with active pathological bleeding or a history of intracranial hemorrhage
  • Do not start BRILINTA in patients undergoing urgent coronary artery bypass graft surgery
  • If possible, manage bleeding without discontinuing BRILINTA. Stopping BRILINTA increases the risk of subsequent cardiovascular events

CONTRAINDICATIONS

  • BRILINTA is contraindicated in patients with a history of intracranial hemorrhage or active pathological bleeding such as peptic ulcer or intracranial hemorrhage. BRILINTA is also contraindicated in patients with hypersensitivity (eg, angioedema) to ticagrelor or any component of the product

WARNINGS AND PRECAUTIONS

  • Dyspnea was reported more frequently with BRILINTA than in patients treated with control agents. Dyspnea from BRILINTA is often self-limiting
  • In patients being treated for coronary artery disease, discontinuation of BRILINTA will increase the risk of MI, stroke, and death. When possible, interrupt therapy with BRILINTA for 5 days prior to surgery that has a major risk of bleeding. If BRILINTA must be temporarily discontinued, restart as soon as possible
  • Ticagrelor can cause ventricular pauses. Bradyarrhythmias including AV block have been reported in the post-marketing setting. Clinical trials excluded patients at increased risk of bradyarrhythmias not protected by a pacemaker, and they may be at increased risk of developing bradyarrhythmias
  • Avoid use of BRILINTA in patients with severe hepatic impairment. Severe hepatic impairment is likely to increase serum concentration of ticagrelor and there are no studies of BRILINTA in these patients
  • Central sleep apnea (CSA) including Cheyne-Stokes respiration (CSR) has been reported in the post-marketing setting in patients taking ticagrelor, including recurrence or worsening of CSA/CSR following rechallenge
  • In patients with Heparin Induced Thrombocytopenia (HIT): False-negative results for HIT-related platelet functional tests, including the heparin-induced platelet aggregation (HIPA) assay, have been reported with BRILINTA. BRILINTA is not expected to impact PF4 antibody testing for HIT

ADVERSE REACTIONS

  • The most common adverse reactions (>5%) associated with the use of BRILINTA included bleeding and dyspnea

DRUG INTERACTIONS

  • Avoid use with strong CYP3A inhibitors and strong CYP3A inducers. BRILINTA is metabolized by CYP3A4/5. Strong inhibitors substantially increase ticagrelor exposure and so increase the risk of adverse events. Strong inducers substantially reduce ticagrelor exposure and so decrease the efficacy of ticagrelor
  • As with other oral P2Y12 inhibitors, co-administration of opioid agonists delays and reduces the absorption of ticagrelor. Consider the use of a parenteral anti-platelet in ACS patients requiring co-administration
  • Patients receiving more than 40 mg per day of simvastatin or lovastatin may be at increased risk of statin-related adverse events
  • Rosuvastatin plasma concentrations may increase because rosuvastatin is a breast cancer resistance protein (BCRP) substrate. Monitor for statin-related adverse effects
  • Monitor digoxin levels with initiation of, or change in, BRILINTA therapy

SPECIAL POPULATIONS

  • Lactation: Breastfeeding is not recommended

INDICATIONS

BRILINTA is indicated to reduce the risk of cardiovascular death, myocardial infarction (MI), and stroke in patients with acute coronary syndrome (ACS) or a history of myocardial infarction. For at least the first 12 months following ACS, it is superior to clopidogrel. BRILINTA also reduces the risk of stent thrombosis in patients who have been stented for the treatment of ACS.

BRILINTA is indicated to reduce the risk of a first MI or stroke in patients with coronary artery disease (CAD) at high risk for such events. While use is not limited to this setting, the efficacy of ticagrelor was established in a population with type 2 diabetes.

BRILINTA is indicated to reduce the risk of stroke in patients with acute ischemic stroke (NIH Stroke Scale Score ≤5) or high-risk transient ischemic attack (TIA).

DOSING

In the management of ACS, initiate BRILINTA treatment with a 180-mg loading dose. Administer 90 mg twice daily during the first year after an ACS event. After one year administer 60 mg twice daily. Use BRILINTA with a daily maintenance dose of aspirin of 75-100 mg. However, in patients who have undergone PCI, consider single antiplatelet therapy with BRILINTA based on the evolving risk for thrombotic versus bleeding events.

In patients with CAD but no prior stroke or MI, administer 60 mg twice daily. Generally, use BRILINTA with a daily maintenance dose of aspirin of 75 mg to 100 mg.

In patients with acute ischemic stroke or high-risk TIA, initiate treatment with a 180-mg loading dose of BRILINTA and then continue with 90 mg twice daily for up to 30 days. Use BRILINTA with a loading dose of aspirin (300 mg to 325 mg) and a daily maintenance dose of aspirin of 75 mg to 100 mg.

Please read full Prescribing Information, including Boxed WARNING, and Medication Guide.

You may report side effects related to AstraZeneca products.

 

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