Ticagrelor associated with fewer cardiac, bleeding and infection complications as compared to clopidogrel


A blinded review of clinical data from patients in the PLATO trial found that, when compared to clopidogrel, ticagrelor (Brilique/Brilinta, AstraZeneca) was more commonly associated with fewer cardiac, bleeding or infectious complications that directly caused or contributed to death following coronary artery bypass graft surgery. These data were presented at the European Society of Cardiology (ESC) congress in Paris, France.

“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 coronary artery bypass grafting is required,” said Christoph Varenhorst, researcher at the Uppsala Clinical Research Centre, Sweden.


The blinded review categorised differences in causes of post-bypass grafting deaths between treatment arms, and found that total rates of vascular deaths and non-vascular deaths from the time of bypass grafting until study end for the ticagrelor and clopidogrel groups were 4% (25/632) vs. 7.5% (47/629) and 0.6% (4/632) vs. 1.7% (11/629), respectively.


The results showed that 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.


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 patients in PLATO who underwent bypass grafting within seven 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.


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 cardiovascular endpoints in acute coronary syndrome patients, above and beyond those afforded by clopidogrel.


The study demonstrated that treatment with ticagrelor led to a greater reduction in the primary endpoint – a  composite of cardiovascular death, myocardial infarction, 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 cardiovascular death and myocardial infarction 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 ticagrelor for 12 months was associated with a 21% RRR in cardiovascular death (4% vs. 5.1%, 1.1% ARR, p=0.001) and a 16 percent RRR in myocardial infarction compared to clopidogrel  at 12 months (5.8% vs. 6.9%, 1.1% ARR, p<0.005).  


Ticagrelor 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.