New PLATO Sub-Analysis of CABG Patients Presented at ACC

In this study, 48% fewer deaths reported among heart bypass patients taking ticagrelor (BRILINTA™/BRILIQUE™) as compared to clopidogrel

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AstraZeneca

Mar 16, 2010, 11:30 ET

ATLANTA, March 16 /PRNewswire-FirstCall/ -- AstraZeneca (NYSE: AZN) today announced results of a new analysis of the PLATO (A Study of PLATelet Inhibition and Patient Outcomes) study which showed there were fewer deaths in patients with acute coronary syndromes (ACS) who took the investigational oral antiplatelet ticagrelor (BRILINTA™/BRILIQUE™) within seven days prior to having heart bypass surgery (coronary artery bypass graft, CABG) compared to those who took clopidogrel.(1) These data were presented today at the American College of Cardiology (ACC) meeting in Atlanta, Georgia.

"The CABG sub-analysis represents current clinical management of patients with ACS,"(1) said Dr. Claes Held, PhD, Associate Professor of Cardiology at the Uppsala Clinical Research Center and Department of Cardiology, and the sub-study's lead researcher. "The effects of ticagrelor compared to clopidogrel showed a reduction of total mortality by 51% and CV death by 48%."(1)

This analysis included 1261 patients who were on study medication up to seven days prior to stopping study medication due to the need for urgent CABG surgery at any time after their ACS event.(1) The patients randomized to ticagrelor had a significantly lower rate of total and CV death than those randomized to clopidogrel treatment:

Total mortality was reduced by 51% (RRR; p<0.01) with ticagrelor (4.6% of 632) compared to clopidogrel (9.2% of 629)(1)
CV death was reduced by 48% (RRR; p<0.01) with ticagrelor (4.0% of 632) compared to clopidogrel (7.5% of 629)(1)
Rate of the primary endpoint (composite of CV death, myocardial infarction, or stroke) from the time of CABG was 10.5% (66/632) with ticagrelor and 12.6% (79/629) with clopidogrel (HR 0.84; CI 0.60-1.16, p=0.29)(1)

Additionally, there was no significant difference in CABG-related major bleeding for ticagrelor compared to clopidogrel,(1) according to both the PLATO and TIMI bleeding criteria respectively (81% for ticagrelor vs. 80% for clopidogrel, and 59% for ticagrelor vs. 58% for clopidogrel for PLATO-defined and TIMI-defined, respectively).

"These treatment comparisons were consistent with the effects seen in the overall PLATO trial," said Dr. Claes Held.(1,2)

About CABG (Coronary Artery Bypass Grafting)

CABG surgery is advised for certain ACS patients, including those who are not candidates for percutaneous coronary intervention (PCI). It is not always known which ACS patients will be advised for CABG surgery at the time of initiating oral antiplatelet therapy.(3) These patients have significant narrowing and blockages of the heart arteries (coronary artery disease).(4) CABG is a type of heart surgery that reroutes, or "bypasses," blood around clogged arteries to improve blood flow and oxygen to the heart.(5)

About PLATO CABG analysis

In the PLATO study, a double-dummy, double-blind randomized trial comparing ticagrelor plus aspirin with clopidogrel plus aspirin in patients with ACS, 1899 patients underwent CABG during the trial.(1) The trial recommended administration of ticagrelor/placebo-clopidogrel to be withheld for 24-72 hours and clopidogrel/placebo-ticagrelor for 5 days prior to CABG surgery. In the exploratory analysis, 1261 patients received study-drug up to seven days prior to CABG surgery.(1) The analysis counted events occurring from after the CABG procedure until the end of the study.(1)

Primary results from PLATO were presented at the European Society of Cardiology and simultaneously published in The New England Journal of Medicine in August 2009.(2)

About BRILINTA™/BRILIQUE™

Ticagrelor (BRILINTA™/BRILIQUE™) is an investigational oral antiplatelet treatment for ACS. Ticagrelor, a cyclo-pentyl-triazolo-pyrimidines (CPTP), is in a chemical class of anti-platelet agents that works differently than thienopyridines, such as clopidogrel and prasugrel, by binding reversibly to the P2Y12 receptor. Ticagrelor is the first reversibly binding oral ADP receptor antagonist.

Ticagrelor is currently under regulatory review in the US and in Europe. BRILINTA and BRILIQUE are trademarks of the AstraZeneca group of companies.

About AstraZeneca

AstraZeneca 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™ Prescription Savings programs, please visit: www.astrazeneca-us.com or call 1-800-AZandMe (292-6363).

References:

(1)Held. Ticagrelor Versus Clopidogrel In Patients With Acute Coronary Syndromes Treated With Coronary Artery Bypass Surgery: Results from The Plato Trial. Presented at 59th Annual Scientific Session, March 16, 2010; Atlanta Georgia. ACC Abstract Number 10-A-9909-ACC.

(2) Wallentin L, Becker R, et al. Ticagrelor versus Clopidogrel in Patients with Acute Coronary Syndromes. N Engl J Med 2009; 361: 1-13.

(3) Kushner, F., Hand, M., et al. 2009 Focused Updates: ACC/ AHA Guidelines for the Management of Patients with ST-Elevation Myocardial Infection (Updating the 2004 Guideline and 2007 Focused Update) and ACC/AHA/SCAI Guidelines on Percutaneous Coronary Intervention (Updating the 2005 Guideline and 2007 Focused Update): A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation 2009; 120: 2271-2306.

(4) American Heart Association. Acute Coronary Syndrome. Available at: http://www.americanheart.org/presenter.jhtml?identifier=3010002. Accessed on February 24, 2010.

(5) American Heart Association. Cardiac Procedures and Surgeries at a glance. Available at: http://www.americanheart.org/presenter.jhtml?identifier=3054086. Accessed on February 24, 2010.

SOURCE AstraZeneca