"These data may help to further understand the factors that contribute to the ability of ticagrelor to provide superior outcomes over clopidogrel in acute coronary syndrome patients, including when a surgical intervention like CABG is required," said Christoph Varenhorst, MD, Researcher at the Uppsala Clinical Research Centre.

The blinded review (Abstract #83082) categorised differences in causes of post-CABG deaths between treatment arms, and found that total rates of vascular deaths and non-vascular deaths from the time of CABG until study end for the ticagrelor and clopidogrel groups were 4.0% (25/632) vs. 7.5% (47/629) and 0.6% (4/632) vs. 1.7% (11/629), respectively. Results showed there were numerically fewer cardiovascular-related deaths from heart attack, heart failure, arrhythmia/sudden death, haemorrhagic stroke/intracranial haemorrhage and bleeding/other haemorrhage among patients treated with ticagrelor compared to clopidogrel (1.6% vs. 2.2%; 0.9 vs. 1.4%; 0.5% vs. 1.4%; 0.0% vs. 0.5%; 0.3% vs. 0.6%). Among factors directly causing or contributing to death, bleeding (27 vs. 9, p=0.002) and infection (16 vs. 6, p=0.033) occurred more commonly in the clopidogrel group, compared to the ticagrelor group.

This blinded review is a follow-up to an analysis presented at the American College of Cardiology (ACC) Annual Scientific Sessions in March 2010. That analysis, which included the 1,261 acute coronary syndrome (ACS) patients in PLATO who underwent CABG within 7 days after discontinuing either clopidogrel or ticagrelor (ticagrelor n=632 and clopidogrel n=629), showed a reduction in total mortality of 51% with ticagrelor. Since the 2010 analysis recognised causes of death as vascular or non-vascular only, there was a need to further investigate the causes of post-CABG deaths between the treatment arms, the results of which were presented today.

AstraZeneca also presented today at the ESC meeting two additional analyses from the PLATO trial.

One analysis (Abstract # 86176) examined the impact of ticagrelor versus clopidogrel on stent thrombosis in ACS patients hospitalised with or without ST-elevation ACS. The data from this analysis showed that ticagrelor reduced definite stent thrombosis compared with clopidogrel, independent of type of ACS, diabetes status, stent type, loading dose of aspirin and dose of clopidogrel pre-randomisation (1.37% vs. 1.93%, HR 0.67, p=0.0091).

The greatest reductions for ticagrelor were demonstrated for both late (>30 days, HR 0.48) and sub-acute stent thrombosis (24 h-30 days, HR 0.60). Prior stroke, peripheral artery disease, ST-elevation ACS and higher heart rate were predictors of definite stent thrombosis.

The other analysis (Abstract #86010) investigated cystatin C, a blood biomarker and indicator of kidney function, as an independent risk predictor for death or heart attack in patients with ST-elevation myocardial infarction (STEMI) or non-ST-elevation myocardial infarction (NSTEMI) ACS.

About PLATO
PLATO was a large (18,624 patients in 43 countries), head-to-head patient outcomes study of ticagrelor versus clopidogrel, both given in combination with aspirin and other standard therapy, designed to establish whether ticagrelor could achieve a clinically meaningful reduction in CV end points in ACS patients, above and beyond those afforded by clopidogrel.

The study demonstrated that treatment with BRILINTA led to a 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 study also demonstrated that treatment with BRILINTA for 12 months was associated with a 21 percent RRR in CV death (4% vs. 5.1%, 1.1% ARR, p=0.001) and a 16 percent RRR in MI compared to clopidogrel at 12 months (5.8% vs. 6.9%, 1.1% ARR, p<0.005).

The results of this analysis formed the basis of the recommendation in all of the approved BRILINTA labels that patients taking BRILINTA should also take a low-maintenance dose of aspirin daily, unless specifically contraindicated.

About CABG
CABG (coronary artery bypass graft) is a type of heart surgery that re-routes, or "bypasses", blood around clogged arteries to improve blood flow and oxygen to the heart. CABG surgery is advised for certain ACS patients, including those who are not candidates for the artery opening procedure known as percutaneous coronary intervention (PCI). Because of the risk of bleeding associated with oral antiplatelets like clopidogrel and ticagrelor, it is recommended that patients planned for CABG surgery discontinue oral antiplatelet therapy use prior to surgery. However it is not always known which ACS patients will be directed for CABG surgery at the time of their ACS event or when oral antiplatelet therapy is initiated.

About BRILINTA (ticagrelor tablets)
BRILINTA is an oral antiplatelet treatment for ACS. BRILINTA is a direct-acting P2Y12 receptor antagonist in a new chemical class called cyclopentyltriazolopyrimidines (CPTPs). BRILINTA is the first reversibly-binding oral ADP receptor antagonist to be approved for use in ACS.

BRILINTA has now been approved in 43 countries, including in the European Union under the trade name BRILIQUE and in the United States, Canada, Brazil, Malaysia and Macau under the trade name BRILINTA. BRILINTA is currently under regulatory review in 49 countries, including, Russia, India and China.

BRILINTA and BRILIQUE are trademarks of the AstraZeneca group of companies. For detailed information regarding BRILINTA / BRILIQUE, please refer to the local Summary of Product Characteristics.

About AstraZeneca
AstraZeneca is a global, innovation-driven biopharmaceutical business with a primary focus on the discovery, development and commercialisation of prescription medicines. As a leader in gastrointestinal, cardiovascular, neuroscience, respiratory and inflammation, oncology and infectious disease medicines, AstraZeneca generated global revenues of US $33.3 billion in 2010.