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Press release from Business Wire

New Sub-Analysis of PLATO ACS Study Suggests Patient Types and Stent Types Had No Impact on Findings of Reduced Rate of Stent Thrombosis With BRILINTA (ticagrelor)

<p class='bwalignc'> <i>PLATO sub-analysis on the effects of BRILINTA of stent thrombosis in NSTEMI and STEMI patients published in Circulation</i> </p> <p class='bwalignc'> </p>

Wednesday, July 31, 2013

New Sub-Analysis of PLATO ACS Study Suggests Patient Types and Stent Types Had No Impact on Findings of Reduced Rate of Stent Thrombosis With BRILINTA (ticagrelor)

10:10 EDT Wednesday, July 31, 2013

WILMINGTON, Del. (Business Wire) -- AstraZeneca (NYSE: AZN) today announced results from a new sub-analysis of the PLATO study that evaluated the incidence of stent thrombosis in patients with acute coronary syndrome (ACS). In the PLATO study, ACS patients who were treated with percutaneous coronary intervention (PCI) and who received drug-eluting or bare metal stents demonstrated a lower risk of stent thrombosis with BRILINTA® (ticagrelor) tablets plus aspirin than with clopidogrel plus aspirin. This analysis suggests that the reduction of stent thrombosis seen with BRILINTA in the PLATO study was consistent in non–ST-elevation myocardial infarction (NSTEMI) and ST-elevation myocardial infarction (STEMI) patients, as well as stent types (bare-metal or drug-eluting stent). These data have been published in the online issue of Circulation, currently available online.

“Stent thrombosis is a life-threatening complication that may occur after stent placement and is more frequent when platelet inhibition is inadequate,” said Dr. James Blasetto, Vice President, US Medical Affairs and Strategic Development. “This important sub-analysis suggests that the benefits of BRILINTA in reducing stent thrombosis are consistent across a broad range of ACS patients regardless of stent type or other characteristics.”

Specific data from this sub-analysis showed:

  • Among the 18,624 patients hospitalized with ACS, 11,289 (60.6%) either had a previous stent implanted (n=1,404) or underwent stenting during the course of the trial (n=9,885).
  • In the PLATO study, BRILINTA plus aspirin reduced stent thrombosis vs clopidogrel plus aspirin at one year: for adjucated “definite” 1.3% (n=71) vs 1.9% (n=106) (HR, 0.67 [95% confidence interval (CI), 0.50-0.91]; P=0.009).
  • The reduction in definite stent thrombosis was evaluated among numerous factors including ACS type (NSTEMI or STEMI), diabetes, stent type (drug-eluting or bare metal), CYP2C19 genetic status, dose of clopidogrel pre-randomization, or use of GPIIb/IIIa inhibitors at randomization. This analysis showed no statistical interaction for the factors evaluated.
  • The reduction in definite stent thrombosis with ticagrelor was also evaluated for late (> 30 days), sub-acute (24 hours – 30 days) and acute (< 24 hours) stent thrombosis.
  • In the PLATO study overall, there was no significant difference in Total Major Bleeding at 12 months (which includes Fatal and Life-threatening bleeding) for BRILINTA vs clopidogrel (11.6% vs 11.2%). There was a somewhat greater risk of Non–CABG-related Major plus Minor Bleeding for BRILINTA vs clopidogrel (8.7% vs 7.0%) and Non–CABG-related Major Bleeding (4.5% vs 3.8%), respectively. PLATO trial did not show an advantage for BRILINTA compared with clopidogrel for CABG-related Bleeding (Total Major 85.8% vs 86.9% and Fatal/Life-threatening 48.1% vs 47.9%, respectively).*

BRILINTA is indicated to reduce the rate of thrombotic cardiovascular (CV) events in patients with ACS (unstable angina [UA], non–ST-elevation myocardial infarction [NSTEMI], or ST-elevation myocardial infarction [STEMI]). In PLATO, BRILINTA has been shown to reduce the rate of a combined end point of CV death, myocardial infarction (MI), or stroke compared to clopidogrel. In PLATO, the difference between treatments was driven by CV death and MI with no difference in stroke. In patients treated with an artery-opening procedure known as percutaneous coronary intervention (PCI), BRILINTA reduces the rate of stent thrombosis.

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

IMPORTANT SAFETY INFORMATION ABOUT BRILINTA (ticagrelor)

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 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. BRILINTA is also contraindicated in patients with hypersensitivity (e.g. angioedema) to ticagrelor or any component of the product.

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

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/Safety/MedWatch or call 1-800-FDA-1088.

For patients prescribed BRILINTA, a savings card program is available, subject to eligibility rules and restrictions. Commercially insured and cash-paying patients may be eligible for one free 30-day prescription and can save up to $825 per year on their next 11 refills. For each refill (a 30-day supply of up to 60 tablets), savings may apply after the first $18 spent by a patient, up to a $75 savings limit. Patients covered through Medicare, Medicaid or similar federal or state programs may be eligible for one month free prescription. Patients can find out more at www.BRILINTAtouchpoints.com or by calling 1-888-412-7454.

AstraZeneca also offers a US patient assistance program for BRILINTA through its AZ&MeTM Prescription Savings Program. To determine eligibility, patients can visit www.AZandMe.com or call 1-800-AZandMe (292-6363).

NOTES TO EDITORS

About BRILINTA ® (ticagrelor) tablets

BRILINTA is an oral antiplatelet treatment for ACS. BRILINTA is a direct-acting P2Y12 receptor antagonist in a chemical class called cyclopentyltriazolopyrimidines (CPTPs). BRILINTA works by inhibiting platelet activation and has been shown to reduce the rate of thrombotic CV events, such as a heart attack or CV death, in patients with ACS.

BRILINTA is available in 90-mg tablets to be administered with a single 180-mg oral loading dose (two 90-mg tablets) followed by a twice daily, 90-mg maintenance dose. Following an initial loading dose of aspirin, BRILINTA should be used with a maintenance dose of 75 mg - 100 mg aspirin once daily, 81-mg aspirin dose in the US.

BRILINTA is a registered trademark of the AstraZeneca group of companies.

About PLATO

PLATO (PLATelet Inhibition and Patient Outcomes) was a large (18,624 patients in 43 countries), head-to-head patient outcomes study of BRILINTA vs clopidogrel, both given in combination with aspirin and other standard therapy. The study was designed to establish whether BRILINTA (ticagrelor) could achieve a clinically meaningful reduction in cardiovascular (CV) events in acute coronary syndrome (ACS) patients, above and beyond that afforded by clopidogrel. Patients were treated for at least 6 months and up to 12 months.

PLATO demonstrated that treatment with BRILINTA led to a significantly greater reduction in the primary end point – a composite of CV death, MI (excluding silent MI), or stroke – compared to patients who received clopidogrel (9.8% vs 11.7% at 12 months; 1.9% absolute risk reduction [ARR]; 16% relative risk reduction [RRR]; 95% CI, 0.77 to 0.92; P<0.001). The difference in treatments was driven by CV death and MI with no difference in stroke. In PLATO, the absolute difference in treatment benefit vs clopidogrel was seen at 30 days and the Kaplan-Meier survival curves continued to diverge throughout the 12-month treatment period.

The PLATO study also demonstrated that treatment with BRILINTA for 12 months was associated with a 21% RRR in CV death (4% vs 5.1%; 1.1% ARR; P=0.001) and a 16% RRR in MI (excluding silent MI) compared to clopidogrel at 12 months (5.8% vs 6.9%; 1.1% ARR; P<0.005).

The primary safety end point in the PLATO study was Total Major Bleeding at 12 months (11.6% for BRILINTA and 11.2% for clopidogrel). In PLATO, non-CABG major + minor bleeding events were more common with BRILINTA vs clopidogrel (8.7% vs 7% respectively). The rate of non-CABG-related major bleeding was higher for BRILINTA (4.5%) vs clopidogrel (3.8%).

Dyspnea was reported in 14% of patients treated with BRILINTA and in 8% of patients treated with clopidogrel. Dyspnea was usually mild to moderate in intensity and often resolved during continued treatment.

* PLATO used the following bleeding severity categorization: Major Bleed–Fatal/Life-threatening. Any one of the following: fatal; intracranial; intrapericardial bleed with cardiac tamponade; hypovolemic shock or severe hypotension due to bleeding and requiring pressors or surgery; clinically overt or apparent bleeding associated with a decrease in hemoglobin (Hb) of more than 5 g/dL; transfusion of 4 or more units (whole blood or packed red blood cells [PRBCs]) for bleeding. Major Bleed–Other. Any one of the following: significantly disabling (eg, intraocular with permanent vision loss); clinically overt or apparent bleeding associated with a decrease in Hb of 3 g/dL; transfusion of 2-3 units (whole blood or PRBCs) for bleeding. Minor Bleed. Requires medical intervention to stop or treat bleeding (eg, epistaxis requiring visit to medical facility for packing). Minimal Bleed. All others (eg, bruising, bleeding gums, oozing from injection sites, etc) not requiring intervention or treatment.

About Acute Coronary Syndrome (ACS)

ACS is an umbrella term for conditions that result from insufficient blood supply to the heart muscle. These conditions include unstable angina (UA), non–ST-elevation myocardial infarction (NSTEMI), and ST-elevation myocardial infarction (STEMI). The conditions are defined by ECG changes and heart muscle enzyme leakage. Non–ST-elevation acute coronary syndrome (NSTE-ACS) includes unstable angina (UA) and non–ST-elevation myocardial infarction (NSTEMI); the term is usually used before heart muscle enzymes have been analyzed.

About AstraZeneca

AstraZeneca is a global, innovation-driven biopharmaceutical business with a primary focus on the discovery, development and commercialization of prescription medicines for gastrointestinal, cardiovascular, neuroscience, respiratory and inflammation, oncology and infectious disease. AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide.

For more information about AstraZeneca in the US or our AZ&Me™ Prescription Savings programs, please visit: www.astrazeneca-us.com or call 1-800-AZandMe (292-6363).

2293500 7/13

AstraZeneca
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or
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or
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