PLATO Efficacy

BRILINTA is indicated to reduce the rate of thrombotic cardiovascular (CV) events* in a broad range of acute coronary syndrome (ACS) patients^†

BRILINTA is indicated to reduce the rate of thrombotic cardiovascular (CV) events in patients with acute coronary syndrome (ACS) (unstable angina, non–ST-elevation myocardial infarction, or ST-elevation myocardial infarction). BRILINTA has been shown to reduce the rate of a combined end point of CV death, myocardial infarction (MI), or stroke compared to clopidogrel. The difference between treatments was driven by CV death and MI with no difference in stroke. In patients treated with PCI, it also reduces the rate of stent thrombosis.

BRILINTA has been studied in ACS in combination with aspirin. Maintenance doses of aspirin >100 mg decreased the effectiveness of BRILINTA. Avoid maintenance doses of aspirin >100 mg daily.

BRILINTA significantly reduced thrombotic CV events vs clopidogrel

Reduction in composite end point vs clopidogrel

^aExcluding silent myocardial infarction (MI).

^bRRR=relative risk reduction.

^cNumber needed to treat (NNT)=1/ARR; ARR=11.67%-9.8%=1.87%; 1/0.0187=53.5.

The PLATO (PLATelet Inhibition and Patient Outcomes) study was a randomized, double-blind, parallel-group trial comparing 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 CV events in 18,624 patients admitted to the hospital within 24 hours of symptom onset of ACS (UA [unstable angina], NSTEMI [non–ST-elevation MI], or STEMI [ST-elevation MI]). Patients were treated for at least 6 months and up to 12 months.

More information about the PLATO Study

• BRILINTA and clopidogrel were studied with aspirin and other standard therapies
• The curves separate by 30 days (RRR 12%) and the separation continues to increase throughout the 12-month treatment period (RRR 16%)

BRILINTA has been studied in ACS in combination with aspirin. Maintenance doses of aspirin >100 mg decreased the effectiveness of BRILINTA. Avoid maintenance doses of aspirin >100 mg daily.

The first and only OAP** FDA-approved to significantly reduce CV death vs clopidogrel¹

Reduction in CV death vs clopidogrel

^aNNT=1/ARR; ARR=5.1%-4.0%=1.1%; 1/0.11=91.

 

Additional secondary end points at 12 months

Outcomes (K-M%)	BRILINTA + aspirin (n=9,333)	Clopidogrel + aspirin (n=9,291)	Hazard Ratio (95% Cl)	P value
MI (excluding silent MI)a	5.8	6.9	0.84 (0.75 - 0.95)	0.0045
Strokea	1.5	1.3	1.17 (0.91 - 1.52)	0.22

 

^aIncludes patients that could have had other nonfatal events or died.

**OAP=Oral antiplatelet.

BRILINTA has been studied in ACS in combination with aspirin. Maintenance doses of aspirin >100 mg decreased the effectiveness of BRILINTA. Avoid maintenance doses of aspirin >100 mg daily.

NEXT: PLATO Safety Information

IMPORTANT SAFETY INFORMATION ABOUT BRILINTA

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 planned to undergo urgent coronary artery bypass graft surgery (CABG). When possible, discontinue BRILINTA at least 5 days prior to any surgery
• Suspect bleeding in any patient who is hypotensive and has recently undergone coronary angiography, percutaneous coronary intervention (PCI), CABG, or other surgical procedures in the setting of BRILINTA
• If possible, manage bleeding without discontinuing BRILINTA. Stopping BRILINTA increases the risk of subsequent cardiovascular events

WARNING: ASPIRIN DOSE AND BRILINTA EFFECTIVENESS

• Maintenance doses of aspirin above 100 mg reduce the effectiveness of BRILINTA and should be avoided. After any initial dose, use with aspirin 75 mg - 100 mg per day

CONTRAINDICATIONS

• BRILINTA is contraindicated in patients with a history of intracranial hemorrhage and active pathological bleeding such as peptic ulcer or intracranial hemorrhage. BRILINTA is also contraindicated in patients with severe hepatic impairment because of a probable increase in exposure; it has not been studied in these patients. Severe hepatic impairment increases the risk of bleeding because of reduced synthesis of coagulation proteins

WARNINGS AND PRECAUTIONS

• Moderate Hepatic Impairment: Consider the risks and benefits of treatment, noting the probable increase in exposure to ticagrelor
• Premature discontinuation increases the risk of MI, stent thrombosis, and death
• Dyspnea was reported in 14% of patients treated with BRILINTA and in 8% of patients taking clopidogrel. Dyspnea resulting from BRILINTA is self-limiting. Rule out other causes
• BRILINTA is metabolized by CYP3A4/5. Avoid use with strong CYP3A inhibitors and potent CYP3A inducers. Avoid simvastatin and lovastatin doses >40 mg
• Monitor digoxin levels with initiation of, or any change in, BRILINTA therapy

ADVERSE REACTIONS

• The most commonly observed adverse reactions associated with the use of BRILINTA vs clopidogrel were Total Major Bleeding (11.6% vs 11.2%) and dyspnea (14% vs 8%)
• In clinical studies, BRILINTA has been shown to increase the occurrence of Holter-detected bradyarrhythmias. PLATO excluded patients at increased risk of bradycardic events. Consider the risks and benefits of treatment

INDICATIONS

BRILINTA is indicated to reduce the rate of thrombotic cardiovascular (CV) events in patients with acute coronary syndrome (ACS) (unstable angina, non–ST-elevation myocardial infarction, or ST-elevation myocardial infarction). BRILINTA has been shown to reduce the rate of a combined end point of CV death, myocardial infarction (MI), or stroke compared to clopidogrel. The difference between treatments was driven by CV death and MI with no difference in stroke. In patients treated with PCI, it also reduces the rate of stent thrombosis.

BRILINTA has been studied in ACS in combination with aspirin. Maintenance doses of aspirin >100 mg decreased the effectiveness of BRILINTA. Avoid maintenance doses of aspirin >100 mg daily.

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

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.FDA.gov/medwatch or call 1-800-FDA-1088.

REFERENCES:

1. Data on file, 1343803, AstraZeneca.
2. 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 Appendix.

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This product information is intended for US health care professionals only.

© 2012 AstraZeneca. 426606-1764500 4/12