PLATO* Efficacy

BRILINTA 90 mg was studied versus clopidogrel in the PLATO trial. Both study arms were studied with aspirin and other standard therapies. The study included patients with acute coronary syndrome (ACS) including STEMI (ST-elevation myocardial infarction), NSTEMI (non–ST-elevation myocardial infarction), and UA (Unstable Angina) patients.

PLATO

SECONDARY EFFICACY END POINT
CV death at 12 MONTHS1,2

PLATO Secondary End Points

ADDITIONAL SECONDARY EFFICACY END POINTS AT 12 MONTHS2

BRILINTA® (ticagrelor) tablets additional secondary efficacy end points
  • Due to the hierarchical test sequence in PLATO, all-cause mortality was an exploratory analysis and, therefore, the P value is nominal

NNT was 91; NNT=1/ARR; ARR=5.1%–4.0%=1.1%; NNT=1/0.011=90.9.
§Excluding silent MI.
Includes patients who could have had other nonfatal events or died.

PLATO

PRIMARY EFFICACY END POINT : SUPERIOR THROMBOTIC CV EVENT REDUCTION
VS CLOPIDOGREL AT 12 MONTHS: COMPOSITE OF CV DEATH , MI,§ OR STROKE1,2

PLATO Primary End Point

DIFFERENCE BETWEEN TREATMENTS WAS DRIVEN BY
CV DEATH AND MI WITH NO DIFFERENCE IN STROKE

  • BRILINTA 90 mg and clopidogrel were studied with aspirin and other standard therapies
  • At 30 days, BRILINTA 90 mg + aspirin reduced the primary composite end point of CV death, MI, or stroke by 12% RRR (ARR 0.6%) vs clopidogrel plus aspirin (4.8% vs 5.4%; HR 0.88, 95% CI: 0.77–1.0)1,2

NNT was 54; NNT=1/ARR; ARR=11.67%–9.8%=1.87%; NNT=1/0.0187=53.5.
K-M=Kaplan-Meier; NNT=number needed to treat.

PLATO Safety

Review the safety results, including bleeding and other adverse reactions from the PLATO study.

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Stent Thrombosis

BRILINTA 90 mg also reduces the rate of stent thrombosis in patients who have been stented for treatment of ACS.2

BRILINTA 90 mg provided greater protection from stent thrombosis vs clopidogrel2

Definite stent thrombosis at 12 months in patients receiving any stent1,2

BRILINTA® (ticagrelor) tablets provided greater protection from stent thrombosis

Chart Summary

  • 33% RRR (0.6% Absolute Risk Reduction) in definite stent thrombosis with BRILINTA 90 mg plus aspirin vs clopidogrel plus aspirin: 1.3% vs 1.9%; Hazard Ratio 0.67 (95% Confidence Interval 0.50-0.91); P=0.0091
  • 11,289 patients with percutaneous coronary intervention (PCI) received a stent during PLATO 
  • Results were similar for drug-eluting and bare-metal stents

RRR=relative risk reduction.
K-M=Kaplan-Meier.

IMPORTANT SAFETY INFORMATION FOR BRILINTA® (ticagrelor) 60-mg AND 90-mg TABLETS
WARNING: (A) BLEEDING RISK, (B) ASPIRIN DOSE AND BRILINTA EFFECTIVENESS

A. 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
1975408-3218312 Last Updated 10/16

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

WARNING: (A) BLEEDING RISK, (B) ASPIRIN DOSE AND BRILINTA EFFECTIVENESS A. 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

B. ASPIRIN DOSE AND BRILINTA EFFECTIVENESS

  • Maintenance doses of aspirin above 100 mg reduce the effectiveness of BRILINTA and should be avoided

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 in about 14% of patients treated with BRILINTA, more frequently than in patients treated with control agents. Dyspnea resulting from BRILINTA is often self-limiting
  • 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. PLATO and PEGASUS excluded patients at increased risk of bradyarrhythmias not protected by a pacemaker, and they may be at increased risk of developing bradyarrhythmias with ticagrelor
  • 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

ADVERSE REACTIONS

  • The most common adverse reactions associated with the use of BRILINTA included bleeding and dyspnea: In PLATO, for BRILINTA vs clopidogrel, non-CABG PLATO-defined major bleeding (3.9% vs 3.3%) and dyspnea (14% vs 8%); in PEGASUS, BRILINTA vs aspirin alone, TIMI Total Major bleeding (1.7% vs 0.8%) and dyspnea (14% vs 6%)

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
  • Patients receiving more than 40 mg per day of simvastatin or lovastatin may be at increased risk of statin-related adverse events
  • Monitor digoxin levels with initiation of, or change in, BRILINTA therapy

INDICATIONS

BRILINTA is indicated to reduce the rate 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 rate of stent thrombosis in patients who have been stented for treatment of ACS.

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.

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

*The PLATO study compared BRILINTA (180-mg loading dose, 90 mg 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 with ACS (UA, NSTEMI, STEMI). Patients were treated for at least 6 months and up to 12 months. Patients were excluded if they had a previous intracranial hemorrhage, 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.

REFERENCES:

  1. Wallentin L, Becker RC, Budaj A, et al; for the PLATO Investigators. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2009;361(11):1045-1057 and Appendix.
  2. BRILINTA [package insert]. Wilmington, DE: AstraZeneca; 2016.

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