[October 06, 2014] |
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BRILINTA Preferred Over Clopidogrel in 2014 AHA/ACC Guideline for the Management of Non-ST-Elevation Acute Coronary Syndromes
WILMINGTON, Del. --(Business Wire)--
AstraZeneca (NYSE:AZN) today confirmed that the American Heart
Association (AHA) and American College of Cardiology (ACC) have updated
the guideline for the management of patients with non-ST-elevation acute
coronary syndromes (NSTE-ACS (News - Alert)). The guideline supports differentiation
among currently available P2Y12 inhibitors, including
ticagrelor, clopidogrel, and prasugrel, for these patients. BRILINTA is
now preferred over clopidogrel for the management of NSTE-ACS patients
who undergo an early invasive (angiography with intent for PCI (News - Alert) if
appropriate) or ischemia-guided strategy (i.e., medically managed), or
those who receive a coronary stent. This is the first time the AHA and
ACC have recommended one P2Y12 over another in the treatment
of acute coronary syndrome (ACS).
"AstraZeneca is pleased that the AHA/ACC guideline recognizes the role
of BRILINTA over clopidogrel in the treatment of NSTE-ACS patients undergoing
a broad range of treatment strategies," said Gregory F. Keenan, MD, Vice
President and US Head Medical Officer, AstraZeneca. "This guideline
update demonstrates how the standards of ACS care continue to evolve and
include BRILINTA, reinforcing the confidence the guideline committee has
in both the medicine and the PLATO data that supports these new
recommendations."
This new guideline is based on a review of multiple clinical trials,
including PLATO. There are no clinical outcome trials that compare
prasugrel and BRILINTA. In total, BRILINTA is included in 12 major US
and Global ACS management guidelines and recognized in several of them
as an important part of the standard of care in a broad range of
invasively or noninvasively managed patients with ACS.
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]). 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
percutaneous coronary intervention (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.
The approved Prescribing Information for BRILINTA includes information
about the approved uses for BRILINTA. BRILINTA has two Boxed
WARNINGS, one for bleeding risk and the other for aspirin dose and
reduced BRILINTA effectiveness. The Boxed WARNING on BLEEDING RISK
states, like other antiplatelet agents, BRILINTA can cause
significant, sometimes fatal, bleeding. For ASPIRIN DOSE
AND BRILINTA EFFECTIVNESS, 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. See the
additional Important Safety Information about BRILINTA below.
Following are recommendations within the updated AHA/ACC NSTE-ACS
guideline specific to oral P2Y12 inhibitors only.
Initial Oral Antiplatelet Therapy in
Patients With Definite or Likely NSTE-ACS Treated With an Initial
Invasive or Ischemia-Guided Strategy
Class I*
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1.
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A P2Y12 inhibitor (either clopidogrel
or ticagrelor) in addition to aspirin should be administered for
up to 12 months to all patients with NSTE-ACS without
contraindications who are treated with either an early invasive or
ischemia-guided strategy. Options include:
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a. Clopidogrel: 300-mg or 600-mg loading dose, then 75 mg daily
(Level of Evidence [LOE]: B)
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b. Ticagrelor(§): 180-mg loading dose, then 90 mg twice daily
(LOE: B)
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Class IIa†
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1.
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It is reasonable to use ticagrelor in preference to clopidogrel
for P2Y12 treatment in patients with
NSTE-ACS who undergo an early invasive or ischemia-guided strategy
(LOE: B)
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PCI-Oral Antiplatelet Agents
Class I
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1.
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A loading dose of a P2Y12 receptor
inhibitor should be given before the procedure in patients
undergoing PCI with stenting. (LOE: A) Options include:
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a. Clopidogrel: 600 mg (LOE: B) or
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b. Prasugrel(‡): 60 mg (LOE: B) or
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c. Ticagrelor(§): 180 mg (LOE: B)
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2.
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In patients receiving a stent (bare-metal stent or drug-eluting
stent [DES]) during PCI for NSTE-ACS, P2Y12
inhibitor therapy should be given for at least 12 months. Options
include:
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a. Clopidogrel: 75 mg daily (LOE: B) or
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b. Prasugrel(‡): 10 mg daily (LOE: B) or
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c. Ticagrelor(§): 90 mg twice daily (LOE: B)
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Class IIa
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1.
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It is reasonable to choose ticagrelor over clopidogrel for P2Y12
inhibition treatment in patients with NSTE-ACS treated with an
early invasive strategy and/or coronary stenting (LOE: B)
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2.
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It is reasonable to choose prasugrel over clopidogrel for P2Y12
treatment in patients with NSTE-ACS who undergo PCI who are not at
high risk of bleeding complications (LOE: B)
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3.
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If the risk of morbidity from bleeding outweighs the
anticipated benefit of a recommended duration of P2Y12
inhibitor therapy after stent implantation, earlier
discontinuation (e.g., <12 months) of P2Y12
inhibitor therapy is reasonable (LOE: C)
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Class III: Harm
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1.
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Prasugrel should not be administered to patients with a prior
history of stroke or transient ischemic attack (LOE: B)
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Late Hospital and Posthospital Oral
Antiplatelet Therapy
Class I
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1.
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Aspirin should be continued indefinitely. The maintenance dose
should be 81 mg daily in patients treated with ticagrelor and 81
mg to 325 mg daily in all other patients (LOE: A)
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2.
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In addition to aspirin, a P2Y12
inhibitor (either clopidogrel or ticagrelor) should be continued
for up to 12 months in all patients with NSTE-ACS without
contraindications who are treated with an ischemia-guided
strategy. Options include:
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a. Clopidogrel: 75 mg daily (LOE: B) or
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b. Ticagrelor§: 90 mg twice daily
(LOE: B)
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3.
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In patients receiving a stent (bare-metal stent or DES) during
PCI for NSTE-ACS, P2Y12 inhibitor therapy
should be given for at least 12 months. Options include:
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a. Clopidogrel: 75 mg daily (LOE: B) or
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b. Prasugrel‡: 10 mg daily (LOE: B) or
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c. Ticagrelor§: 90 mg twice daily
(LOE: B)
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Class IIa
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1.
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It is reasonable to choose ticagrelor over clopidogrel for
maintenance P2Y12 treatment in patients
with NSTE-ACS treated with an early invasive strategy and/or PCI
(LOE: B)
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2.
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It is reasonable to choose prasugrel over clopidogrel for
maintenance P2Y12 treatment in patients
with NSTE-ACS who undergo PCI who are not at high risk for
bleeding complications (LOE: B)
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3.
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If the risk of morbidity from bleeding outweighs the
anticipated benefit of a recommended duration of P2Y12
inhibitor therapy after stent implantation, earlier
discontinuation (e.g., <12 months) of P2Y12
inhibitor therapy is reasonable (LOE: C)
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*Class I: Procedure/Treatment SHOULD be performed/administered †Class
II: Additional studies with focused objectives needed. IT IS REASONABLE
to peform procedure/administer treatment ‡Patients should receive a
loading dose of prasugrel provided that they were not pretreated with
another P2Y12 receptor inhibitor §The recommended maintenance dose
of aspirin to be used with ticagrelor is 81 mg daily
To read the full AHA/ACC guideline, please visit: http://circ.ahajournals.org/content/early/2014/09/22/CIR.0000000000000134
IMPORTANT SAFETY INFORMATION ABOUT BRILINTA (ticagrelor)
WARNING: (A) BLEEDING RISK, (B) ASPIRIN DOSE AND BRILINTA
EFFECTIVENESS
A. BLEEDING RISK
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BRILINTA, like other antiplatelet agents, can cause significant,
sometimes fatal, bleeding
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Do not use BRILINTA in patients with active pathological bleeding
or a history of intracranial hemorrhage
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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
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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
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If possible, manage bleeding without discontinuing BRILINTA.
Stopping BRILINTA increases the risk of subsequent cardiovascular
events
B. ASPIRIN DOSE AND BRILINTA EFFECTIVENESS
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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
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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
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Moderate Hepatic Impairment: Consider the risks and benefits of
treatment, noting the probable increase in exposure to ticagrelor
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Premature discontinuation increases the risk of MI, stent thrombosis,
and death
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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
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BRILINTA is metabolized by CYP3A4/5. Avoid use with strong CYP3A
inhibitors and potent CYP3A inducers. Avoid simvastatin and lovastatin
doses >40 mg
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Monitor digoxin levels with initiation of, or any change in, BRILINTA
therapy
ADVERSE REACTIONS
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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%)
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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.
Patients can find out more information about BRILINTA at www.BRILINTAtouchpoints.com
or by calling 1-888-412-7454.
AstraZeneca offers the 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. The
difference between treatments was driven by CV death and MI with no
difference in stroke.
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 could achieve a clinically meaningful
reduction in CV events in ACS patients, above and beyond that afforded
by clopidogrel. Patients were treated for at least six months and up to
12 months.
PLATO? demonstrated that treatment with BRILINTA plus aspirin
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 plus aspirin (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.
The PLATO study also demonstrated that treatment with BRILINTA plus
aspirin 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 plus aspirin 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, which includes Fatal and Life-threatening bleeding, (11.6% for
BRILINTA plus aspirin and 11.2% for clopidogrel plus aspirin) at 12
months. In PLATO, Non-CABG-related 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%). The 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).
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
(e.g., 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
(e.g., epistaxis requiring visit to medical facility for packing). Minimal
Bleed. All others (e.g., 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. The goal of treating ACS is to restore, improve, and/or
stabilize blood flow to the heart muscle and to reduce the risk of
recurrent cardiovascular (CV) events. Depending on the severity of the
condition and the resources available, the patient will either be
managed with medicines or undergo more invasive procedures. These
procedures may include using catheters, balloons, and/or stents that
treat the narrowed arteries of the heart called percutaneous coronary
intervention (PCI) and/or a type of surgery that improves blood flow to
the heart called coronary artery bypass grafting (CABG).
About AstraZeneca AstraZeneca is a global, innovation-driven
biopharmaceutical business that focuses on the discovery, development
and commercialization of prescription medicines, primarily for the
treatment of cardiovascular, metabolic, respiratory, inflammation,
autoimmune, oncology, infection and neuroscience diseases. AstraZeneca
operates in over 100 countries and its innovative medicines are used by
millions of patients worldwide. For more information please visit www.astrazeneca-us.com.
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