PLATO: Causes of lower mortality with ticagrelor identified

Oct 1 2012

By Piriya Mahendra, medwireNews Reporter

The mortality reduction with ticagrelor versus clopidogrel is due to fewer deaths from cardiovascular (CV), bleeding, and infection complications, say researchers.

As reported previously by medwireNews, the Platelet Inhibition and Patient Outcomes (PLATO) trial revealed that the respective 1-year risks for all-cause and CV mortality were 51% and 48% lower among those who took ticagrelor (n=632) than in those who took clopidogrel (n=629) after coronary artery bypass graft (CABG) surgery.

Chrisoph Varenhorst (Uppsala University, Sweden) and colleagues found that this significantly lower total and cardiovascular mortality with ticagrelor was mainly due to the higher number of vascular deaths related to myocardial infarction in the clopidogrel group versus the ticagrelor group, at 14 versus 10.

Heart failure was also more common in the clopidogrel group than the ticagrelor group, at 9 versus 6 events, as was arrhythmia or sudden death, at 9 versus 3 events. Hemorrhagic stroke occurred in seven clopidogrel patients compared with two in the ticagrelor group.

Other factors associated with higher mortality in the clopidogrel-treated patients compared with ticagrelor-treated patients included infections, which occurred in 16 versus six individuals, and bleeding as the primary or contributing cause of death, which occurred in 27 versus 9 individuals.

Indeed, the 12-month rates of bleeding directly causing or contributing to death were 4.6% for clopidogrel versus 1.4% for ticagrelor, corresponding to a hazard ratio of 0.33.

"The more rapid offset of the platelet inhibitory effect after ticagrelor discontinuation may be one reasonable explanation for this association and a contributing factor explaining the difference," suggest Varenhorst and team in the Journal of the American College of Cardiology.

They explain that moderate-to-poor responders to clopidogrel have a similar time to recovery of platelet function compared with ticagrelor-treated patients after cessation of treatment.

"Thus, approximately a third of the patients with high levels of platelet inhibition on clopidogrel need 7 or more days to recover near-normal platelet reactivity, explaining why some clopidogrel-treated patients may be particularly vulnerable to serious hemorrhagic complications," Varenhorst and team write.

They say that further studies are needed to investigate the underlying mechanisms responsible for the improved survival in patients treated with ticagrelor after CABG surgery.

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