Genetic Substudy Shows Fewer Major Cardiovascular Events With Ticagrelor (BRILINTA) Regardless of Relevant Genetic Variability in ACS Patients
WILMINGTON, Del., Aug. 29 /PRNewswire-FirstCall/ -- A new
genetic substudy of PLATO (A Study of PLATelet Inhibition and
Patient Outcomes) showed that the effects on a combined primary
endpoint of cardiovascular death, myocardial infarction, or stroke
seen in Acute Coronary Syndromes (ACS) patients who received the
investigational oral antiplatelet treatment, ticagrelor
(BRILINTA(TM)), were maintained, whether or not they had the
genetic variability that has been previously shown to affect a
patient's response to clopidogrel. The substudy is the first to
look at both efficacy and bleeding endpoints of ACS patients
treated with ticagrelor who carry variations in the CYP2C19 and
ABCB1 genes. The data were presented today at the European Society
of Cardiology (ESC) congress in Stockholm, Sweden and
simultaneously published in The Lancet.
(Logo: http://photos.prnewswire.com/prnh/20091027/PH99766LOGO ) (Logo: http://www.newscom.com/cgi-bin/prnh/20091027/PH99766LOGO ) CYP2C19
Regardless of the CYP2C19 genotype, the primary outcome occurred
less often with ticagrelor versus clopidogrel (interaction p=0.46).
Ticagrelor event rates were 8.6% per year in carriers and 8.8% per
year in non-carriers of CYP2C19 loss-of-function genotype. For
clopidogrel patients that carried the CYP2C19 loss-of-function
alleles, there was a 11.2% per year event rate, compared to 10.0%
per year for patients without the loss of function allele. Similar
to the overall PLATO study, total major bleeding did not
significantly differ between ticagrelor and clopidogrel regardless
of CYP2C19 genotype.
ABCB1
The genetic substudy also investigated ticagrelor and
clopidogrel treatment outcomes in the three genetic groupings of
the ABCB1 gene group; these were defined as high, intermediate and
low expressions of ABCB1, respectively. The primary efficacy event
rates for ticagrelor were: 9.5% per year for low, 8.5% per year for
intermediate, and 8.8% per year for high expression groups. Primary
efficacy event rates for clopidogrel were: 10.5% per year for low,
9.8% per year for intermediate, and 11.9% per year for high
expression groups. There was no relationship between the ABCB1
genotype and bleeding.
"This substudy is the largest database of ACS patients to date
to examine the impact of genetic make-up on response to oral
antiplatelet treatment. As this substudy showed, the effects seen
with ticagrelor were independent of genetic variability in CYP2C19
or ABCB1," said Professor Lars Wallentin, primary investigator of
the PLATO genetic substudy and Professor of Cardiology and Research
Director at the Uppsala University, Sweden.
The substudy was designed to explore the interaction of CYP2C19
and ABCB1 genes on ticagrelor and clopidogrel efficacy and safety.
10,285 ACS patients were genotyped for CYP2C19 and ABCB1 status. On
a background of aspirin, patients in the ticagrelor group were
given a 180 mg loading dose and a 90 mg twice-daily maintenance
dose, while patients in the clopidogrel group were given a 300 mg
to 600 mg loading dose and 75 mg once-daily maintenance dose, for 6
to 12 months.
About ACS
ACS is an umbrella term for conditions that result from a
reduction in blood flow to the heart muscle. These conditions range
from UA (chest pain) to myocardial infarction (MI) (heart
attack):
-- STEMI is a type of heart attack in which the coronary artery is
generally blocked off by a blood clot, and as a result virtually all
the heart muscle being supplied by the affected artery starts to die.
-- UA/NSTEMI is a type of heart attack in which a blood clot partly
occludes an artery and as a result only a portion of the heart muscle
being supplied by the affected artery dies. UA is one of the types of
ACS, a series of conditions most commonly produced by the rupture of a
plaque in a coronary artery. UA is "unstable" not only because a
plaque has potentially ruptured (a situation which threatens to
progress to a myocardial infarction), but also because the symptoms it
produces - the angina - generally occurs more frequently, often at
rest, and lasts longer.
About the PLATO study
PLATO was a large (18,624 patients in 43 countries) head-to-head
patient outcomes study of ticagrelor versus clopidogrel, designed
to establish whether ticagrelor could achieve clinically meaningful
CV and safety end points in ACS patients. PLATO was designed to
reflect current clinical management of ACS patients and included
and represented all types of ACS patients (STEMI, NSTEMI & UA)
whether they underwent invasive procedures or were medically
managed.
About BRILINTA(TM)/BRILIQUE(TM)
Ticagrelor (BRILINTA/BRILIQUE) is an investigational oral
antiplatelet treatment for ACS. Ticagrelor is a direct-acting P2Y12
receptor antagonist in a chemical class called
cyclo-pentyl-triazolo-pyrimidines (CPTPs). Ticagrelor is the first
reversibly-binding oral ADP receptor antagonist.
BRILINTA and BRILIQUE are trademarks of the AstraZeneca group of
companies.
About AstraZeneca
AstraZeneca (NYSE:AZN) is a global, innovation-driven
biopharmaceutical business with a primary focus on the discovery,
development and commercialization, of prescription medicines. As a
leader in gastrointestinal, cardiovascular, neuroscience,
respiratory and inflammation, oncology, and infectious disease
medicines, AstraZeneca generated global revenues of $32.8 billion
in 2009. In the United States, AstraZeneca is a $14.8 billion
healthcare business.
For more information about AstraZeneca in the US or our
AZ&Me(TM) Prescription Savings programs, please visit:
www.astrazeneca-us.com or call 1-800-AZandMe (292-6363).
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Posted: August 2010
