BRILINTA patient enjoying a day in the park
BRILINTA patient enjoying a day in the park

PLATO PRESPECIFIED LANDMARK ANALYSIS—THROMBOTIC CV EVENTS OVER TIME

In patients with ACS, Risk won’t quit.

Neither will BRILINTA.

Prespecified landmark analysis of PLATO—Thrombotic CV events over time1

Thrombotic Analysis of PLATO
Thrombotic Analysis of PLATO

More than half of the ARR with BRILINTA 90 mg plus aspirin was seen after the first 30 days1

PLATO BLEEDING
PLATO PRIMARY EFFICACY
PLATO STUDY DESIGN

*Excluding silent MI.

 

  • Patients were randomized to either BRILINTA or clopidogrel, and the occurrence of the primary composite end point was evaluated from Day 1-30 and Day 31-360. Patients who did not experience an event in the first 30 days continued on their original treatment and were included in the analysis from Day 31-360. This analysis did not evaluate a switch in treatment.1

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PLATO NET BENEFIT ANALYSIS

PLATO: Net benefit analysis2,3

Prespecified PLATO secondary end point

Composite of all-cause mortality (including fatal bleeding and CV death), MI,* and stroke at 12 months

PLATO Net Benefits Analysis
PLATO Net Benefits Analysis
PLATO BLEEDING
CV DEATH
PLATO PRIMARY EFFICACY
PLATO STUDY DESIGN

*Excluding silent MI.

 

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Make SUPERIORITY with BRILINTA your choice

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Know About PLATO Select Analyses

Why choose second best?

Make SUPERIORITY with BRILINTA your choice

Request a Rep

Do you have questions about the PLATO study?

REQUEST A REP

Know About PLATO Select Analyses

NSTEMI FINAL DIAGNOSIS PLATO PRESPECIFIED SUBGROUP ANALYSIS

 

In PLATO patients with ACS, NSTEMI subgroup: BRILINTA vs clopidogrel

Primary end point in the PLATO final diagnosis NSTEMI prespecified subgroup at 12 months

Composite of CV death, MI,* or stroke1,3

PLATO Subgroup Analysis
PLATO Subgroup Analysis
PLATO BLEEDING IN NSTEMI SUBGROUP
PLATO STUDY DESIGN

*Excluding silent MI.

 

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

Additional final diagnosis subgroups

Composite efficacy end point K-M% at 12 months1

     

  • BRILINTA 90 mg plus aspirin vs clopidogrel plus aspirin, respectively:

       

    • STEMI 8.5% (N=3496) vs 10.1% (N=3530), HR: 0.84; 95% CI: 0.72–0.98

      •  

    • UA 8.6% (N=1549) vs 9.1% (N=1563), HR: 0.96; 95% CI: 0.75–1.22
PLATO BLEEDING IN ADDITIONAL FINAL DIAGNOSIS SUBGROUPS
PLATO PRIMARY EFFICACY
PLATO BLEEDING
CV DEATH

PLATO was not designed or powered to demonstrate the efficacy or safety of BRILINTA compared with clopidogrel in specific subgroups. Subgroup analyses were performed to evaluate consistency of results in different cohorts. Analyses must be interpreted cautiously, as differences can reflect the play of chance among a large number of analyses. The final diagnosis subgroup was based on post-randomized determinations.3

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CKD POST HOC ANALYSIS OF PLATO SUBGROUP

 

CKD (CrCl <60 mL/min): BRILINTA vs clopidogrel in PLATO

A post hoc analysis of CV events in the PLATO CKD subgroup at 12 months5

Composite of CV death, MI,* or stroke5

HOC Analysis of PLATO Subgroup
HOC Analysis of PLATO Subgroup
BLEEDING IN CKD PLATO SUBGROUP
PLATO STUDY DESIGN

*Excluding silent MI.

 

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

 

  • Central laboratory serum creatinine levels were available in 15,202 (81.9%) PLATO patients at baseline, and creatinine clearance, estimated by the Cockcroft-Gault equation, was calculated in a post hoc analysis of the subgroup5
  • CKD was defined as creatinine clearance <60 mL/min (n=3237).5 PLATO excluded patients requiring dialysis7
  • No dosage adjustment is needed in patients with renal impairment7

In PLATO non-CKD (CrCl ≥60 mL/min) patients

  • A post hoc analysis of the primary efficacy end point in the non-CKD subgroup (n=11,965), K-M% at 12 months: 7.9% vs 8.9% with BRILINTA and clopidogrel, respectively (HR 0.90; 95% CI 0.79–1.02)5
BLEEDING IN NON-CKD PLATO SUBGROUP
PLATO PRIMARY EFFICACY
PLATO BLEEDING
CV DEATH

PLATO was not designed or powered to demonstrate the efficacy or safety of BRILINTA compared with clopidogrel in specific subgroups. Subgroup analyses were performed to evaluate consistency of results in different cohorts. Analyses must be interpreted cautiously, as differences can reflect the play of chance among a large number of analyses.3

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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.3,7

ACS=acute coronary syndrome; ARR=absolute risk reduction; CI=confidence interval; CKD=chronic kidney disease; CrCl=creatinine clearance; CV=cardiovascular; HR=hazard ratio; K-M=Kaplan-Meier; MI=myocardial infarction; NSTEMI=non–ST-elevation myocardial infarction; PLATO=PLATelet inhibition and patient Outcomes; RRR=relative risk reduction; STEMI=ST-elevation myocardial infarction; UA=unstable angina.

References
  1. US Food and Drug Administration; Center for Drug Evaluation and Research; Division of Cardiovascular and Renal Products. Complete Response Review Addendum. Reviewed June 8, 2011. Accessed April 25, 2024. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022433orig1s000medr.pdf
  2. Data on File, REF-51077, AstraZeneca Pharmaceuticals LP.
  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-72872, AstraZeneca Pharmaceuticals LP.
  5. James S, Budaj A, Aylward P, et al. Ticagrelor versus clopidogrel in acute coronary syndromes in relation to renal function: results from the Platelet Inhibition and Patient Outcomes (PLATO) trial. Circulation. 2010;122(11):1056-1067.
  6. Data on File, REF-51076, AstraZeneca Pharmaceuticals LP.
  7. 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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