New PLATO Analysis Evaluates the Influence of High-Sensitivity Troponin
Biomarker Status in NSTE-ACS Patients Managed with Revascularization or
WILMINGTON, Del. -- November 07, 2012
AstraZeneca (NYSE: AZN) today announced results from a post-hoc analysis of a
sub-group of the PLATO study. This new analysis evaluated outcomes in 9,946
patients with non–ST-elevation acute coronary syndrome (NSTE-ACS) managed with
or without in-hospital revascularization in relation to measurements at
randomization of high-sensitivity troponin-T (hs-TnT), a biomarker test that
may be a more sensitive indicator of ongoing heart muscle damage than
previously available troponin tests.
This study was presented today at the American Heart Association (AHA)
Scientific Sessions in Los Angeles, CA. In the 86.3% (n= 8,587) of NSTE-ACS
patients in PLATO with elevated hs-TnT, BRILINTA^® (ticagrelor) tablets
reduced the composite of cardiovascular (CV) death, myocardial infarction
(MI), and stroke, consistent with the results for the overall population of
the PLATO study. In the 13.7% (n=1,359) patients with normal hs-TnT, the
confidence intervals around the hazard ratios were broad. Because of the
limited number of patients without hs-TnT elevation, uncertainties remain
regarding the effects of ticagrelor versus clopidogrel on outcomes in hs-TnT
“Hs-TnT is an important new biomarker that provides a much better ability to
identify patients with ongoing myocardial damage. This biomarker allowed
identification of NSTE-ACS patients with low levels of myocardial damage that
would not have been detected by previous testing,” said James Ferguson, MD,
Executive Director, Medical Affairs and Strategic Development, and Vice
President for Global Medical Affairs. “This analysis of PLATO shows BRILINTA
reduced the rate of thrombotic CV events in those NSTE-ACS patients with
elevated hs-TNT, both when managed with revascularization as well as when
BRILINTA is indicated to reduce the rate of thrombotic 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, 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.
Bleeding rates and adverse events were not assessed in this sub-group
analysis. 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 versus
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.
Specific findings from this post-hoc analysis include:
*Among patients with elevated hs-TnT (>14 ng/L at entry) who were
revascularized in-hospital (n=5,011), event rates for the composite of CV
death, MI, and stroke were 8.5% for BRILINTA vs 11.2% for clopidogrel
(adjusted hazard ratio [HR], 0.76 [CI 95%, 0.63-0.91]).
*Among patients with elevated hs-TnT managed medically (n=3,576), event
rates for the composite of CV death, MI, and stroke were 12.4% for
BRILINTA vs 14.9% for clopidogrel (adjusted HR, 0.81 [CI 95%, 0.68-0.97]).
*Among patients with normal hs-TnT (<14 ng/L at entry) who were
revascularized in-hospital, (n=346), event rates for the composite of CV
death, MI, and stroke were 12.2% for BRILINTA vs 11.5% for clopidogrel
(adjusted HR, 0.99 [CI 95%, 0.53-1.83]).
*The event rates (composite of CV death, MI, and stroke) were low in the
1,013 medically managed NSTE-ACS patients with normal hs-TnT: 3.1% for
BRILINTA vs 2.4% for clopidogrel (adjusted HR, 1.40 [CI 95%, 0.66-2.97]).
*There was no significant interaction of treatment with hs-TnT status in
patients treated with in-hospital revascularization, but there was an
interaction in patients managed medically.
IMPORTANT SAFETY INFORMATION ABOUT BRILINTA (ticagrelor) TABLETS
WARNING: BLEEDING RISK
*BRILINTA, like other antiplatelet agents, can cause significant, sometimes
*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
*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
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
*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 www.fda.gov/safety/medwatch.
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 www.BRILINTAtouchpoints.com
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 www.AZandMe.com or call 1-800-AZandMe (292-6363).
– ENDS –
NOTES TO EDITORS
About BRILINTA^® (ticagrelor) tablets
BRILINTA is an oral antiplatelet treatment for ACS. BRILINTA is a
direct-acting P2Y 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 versus
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 versus 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 versus 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 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.
AstraZeneca is a global, innovation-driven biopharmaceutical business with a
primary focus on the discovery, development and commercialization of
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