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Better survival with ticagrelor vs. clopidogrel in PLATO analysis

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American College of Cardiology 59th Annual Scientific Session

ATLANTA – Patient with acute coronary syndromes who undergo CABG surgery are less likely to develop fatal outcomes when given ticagrelor, a reversible, more intense P2Y12 receptor antagonist, instead of clopidogrel as antiplatelet therapy, according to results of a subgroup analysis of the PLATO trial.

For the analysis, researchers examined a subgroup of 1,261 patients in the PLATO trial who underwent CABG after randomization. Results revealed that 10.5% of patients who received ticagrelor (n=632; Brilinta, AstraZeneca) plus aspirin within seven days of CABG had a primary composite endpoint that included CV death, MI and stroke compared with 12.6% of patients who received clopidogrel (n=629; Plavix, Sanofi-Aventis) plus aspirin. All antiplatelet therapy was discontinued before patients underwent CABG.

Patients assigned to ticagrelor had a total mortality rate of 4.6% compared with 9.2% for patients assigned clopidogrel. CV death rates were 4% in the ticagrelor group vs. 7.5% in the clopidogrel group.

The researchers noted no statistically significant difference between ticagrelor and clopidogrel for MI and stroke or CABG-related bleeding, when examined separately.

<>“We did see about a 50% reduction in mortality in these patients but without any increase in the bleeding complications. We have looked at several different definitions of bleeding and do not see any sign of increases in bleeding, despite this reduction in mortality,” Claes Held, MD, PhD, associate professor of cardiology at the Uppsala Clinical Research Center in Sweden, said at a press conference.

Held noted that the subgroup analysis results are provocative, but said caution is warranted when interpreting the findings because of PLATO’s retrospective, post-randomization comparison between the treatment arms.

These results are in line with the overall effect of ticagrelor vs. clopidogrel reported in the main findings of PLATO, a double blind study that randomized more than 18,000 patients with ACS to either ticagrelor or clopidogrel. Overall results indicated an efficacy advantage for ticagrelor and no significant difference in major bleeding compared with clopidogrel. The main trial results were presented in August at the European Society of Cardiology Congress 2009 and were published previously in Cardiology Today.

This is a great and important study that raises lots of issues. There wasn’t any difference in major bleeding, and yet the results were better in terms of a reduction in mortality. So the question then is: Are there other effects? A more potent agent should give you more bleeding, but this didn’t. Are there pleiotropic effects of this particular medication?

– David R. Holmes Jr., MD

Cardiology Today Editorial Board member

For more information:

• Held C. LBCT V. Presented at: American College of Cardiology 59th Annual Scientific Sessions; March 13-16, 2010; Atlanta.

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