BRILINTA (Ticagrelor) Receives Additional Class I Recommendation in Updated ACCF/AHA Guidelines for the Management of STEMI

  BRILINTA (Ticagrelor) Receives Additional Class I Recommendation in Updated
  ACCF/AHA Guidelines for the Management of STEMI Patients

 BRILINTA Recognized Across Major US Treatment Guidelines for Acute Coronary

Business Wire

WILMINGTON, Del. -- December 17, 2012

AstraZeneca (NYSE: AZN) announced today that a combined panel of experts from
the American College of Cardiology Foundation (ACCF) and American Heart
Association (AHA) have updated their guidelines to include a Class I
recommendation for use of the oral antiplatelet (OAP) medicine BRILINTA^®
(ticagrelor) tablets in patients with ST-elevation myocardial infarction
(STEMI) managed invasively.^1 With this latest guidelines update, BRILINTA is
included in more than 10 major acute coronary syndrome (ACS) treatment
guidelines globally.^1-11

“The U.S. Cardiology community is again acknowledging the clinical value of
BRILINTA,” said James Ferguson, MD, Executive Director, Medical Affairs and
Strategic Development, US, and Vice President for Global Medical Affairs.
“This significant milestone, along with the inclusion in the NSTEMI Guidelines
in July, solidifies the position of BRILINTA in multiple ACS guidelines as an
important part of standard of care for both STEMI and NSTEMI patients.”^2

A Class I recommendation is the highest recommendation provided by the
guidelines committee.

Following are specific Class I and Class IIa recommendations within the
guidelines relating to OAPs, including BRILINTA, as well as the use of aspirin
(the recommended maintenance dose of aspirin to be used with ticagrelor is 81
mg daily):

Antiplatelet Therapy to Support Primary Percutaneous Coronary Intervention
(PCI) for STEMI: Recommendations

Class I
1. Aspirin 162 to 325 mg should be given before primary PCI. (Level of
Evidence (LOE): B)

2. After PCI, aspirin should be continued indefinitely. (LOE: A)

3. A loading dose of a P2Y[12] receptor inhibitor should be given as early as
possible or at time of primary PCI to patients with STEMI. Options include:
a. Clopidogrel 600 mg (LOE: B); or
b. Prasugrel 60 mg (LOE: B); or
c. Ticagrelor 180 mg (LOE: B)

4. P2Y[12] inhibitor therapy should be given for 1 year to patients with STEMI
who receive a stent (bare-metal stent [BMS] or drug-eluting stent [DES])
during primary PCI using the following maintenance doses:
a. Clopidogrel 75 mg daily (LOE: B); or
b. Prasugrel 10 mg daily (LOE: B); or
c. Ticagrelor 90 mg twice a day (LOE: B)

Class IIa
1. It is reasonable to use 81 mg of aspirin per day in preference to higher
maintenance doses after primary PCI. (LOE: B)

2. It is reasonable to begin treatment with an intravenous GP IIb/IIIa
receptor antagonist such as abciximab (LOE: A), high-bolus-dose tirofiban
(LOE: B), or double-bolus eptifibatide (LOE: B) at the time of primary PCI
(with or without stenting or clopidogrel pre-treatment) in selected patients
with STEMI who are receiving unfractionated heparin (UFH).

BRILINTA Indication

BRILINTA is indicated to reduce the rate of thrombotic cardiovascular (CV)
events in patients with acute coronary syndrome (ACS: unstable angina [UA],
non–ST-elevation myocardial infarction [NSTEMI], or ST-elevation myocardial
infarction [STEMI]). 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 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.

Since receiving FDA approval in July 2011, BRILINTA has now been added to six
established treatment guidelines in the US. In July 2012, a combined panel of
experts from the ACCF and AHA updated their guidelines to include a Class I
recommendation for the use of BRILINTA in patients with Unstable Angina (UA)
or NSTEMI, managed both invasively or non-invasively.^2

In February 2012, the American College of Chest Physicians (ACCP) updated its
guidelines for Antithrombotic Therapy to include a recommendation for
administering BRILINTA with low-dose aspirin to patients in the first year
after ACS who have not undergone PCI or who have undergone PCI with stent
placement. This was the first time that clinical treatment guidelines in the
US specifically suggested use of BRILINTA over clopidogrel, as a grade 2B

In November 2011, a combined expert committee from ACCF, AHA and the Society
for Cardiovascular Angiography and Interventions (SCAI) updated its guidelines
for the management of patients undergoing PCI to provide a Class I
recommendation for giving BRILINTA to patients with ACS undergoing PCI with
stenting.^4 Additionally, AHA/ACCF also revised their Guidelines on Secondary
Prevention and Risk Reduction Therapy to include BRILINTA, in combination with
low-dose aspirin, as a Class I therapy to be taken twice daily for at least 12
months in patients receiving a bare-metal stent (BMS) or drug-eluting stent
(DES) during PCI for ACS.^5

The ACCF/AHA guidelines for CABG, released in November 2011, include a Class I
recommendation that BRILINTA should be discontinued for at least 5 days before
surgery, in patients referred for elective CAGB.^6



  *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


  *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


  *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


  *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
  *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


  *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. This  information can be found  at

You are encouraged to report negative side effects of prescription drugs to
the FDA. Visit.

For patients that require BRILINTA beyond their hospital stay, a savings card
program is available based on eligibility. 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
or by calling 1-888-412-7454.

AstraZeneca also offers a U.S. patient assistance program for BRILINTA through
its AZ&Me^TM Prescription Savings Program. To determine eligibility, patients
can visit or call 1-800-AZandMe (292-6363).


About BRILINTA^® (ticagrelor) tablets

BRILINTA is an oral antiplatelet treatment for ACS. BRILINTA is a
direct-acting P2Y[12] 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.


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 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, 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 compared to clopidogrel at 12 months (5.8% vs 6.9%; 1.1% ARR;

The primary safety end point in the PLATO study was Total Major Bleeding
(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.

About Acute Coronary Syndrome (ACS)

ACS is an umbrella term for conditions that result from insufficient blood
supply to the heart muscle. These conditions range from unstable angina (UA),
non–ST-elevation myocardial infarction (NSTEMI), or ST-elevation myocardial
infarction (STEMI).

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: or call 1-800-AZandMe

^1    O’Gara, P. et al. Circulation. 2012. doi:10.1161/cir.0b013e3182742cf6
^2    Jneid, H. et. al. Journal of the American College of Cardiology. 2012.
^3    Guyatt, G. et. al. Chest. 2012. doi:10.1378/chest.1412S3
^4    Levine, G. et. al. Journal of the American College of Cardiology. 2011.
^5    Smith, S. et. al. Circulation. 2011. doi:10.1161/cir.0b013e318235eb4d
^6    Hillis, D. et. al. Journal of the American College of Cardiology. 2011.
^7    Steg, G. et. al. European Heart Journal. 2012.
^8    Hamm, C. et. al. European Heart Journal. 2011.
^9    Wijns, W. et. al. European Heart Journal. 2010.
^10   Perk, J. et. al. European Heart Journal. 2012.
^11   Bell, A. et. al. Canadian Journal of Cardiology. 2011.

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