Phase III success for platelet inhibitor

AstraZeneca, manufacturer of ticagrelor, announced the results of the PLATO study on 30 August at the European Society of Cardiology congress and in the New England Journal of Medicine.¹ Data from 18,624 patients showed that ticagrelor significantly reduced the combined rate of myocardial infarction, stroke or cardiovascular death compared with clopidogrel.

Like clopidogrel, ticagrelor is an orally administered inhibitor of the ADP receptor P2Y12 – a key mediator of platelet activation and aggregation. Unlike clopidogrel, however, ticagrelor is not a prodrug. Consequently, it has a faster and greater effect on P2Y12.

The PLATO study included patients both with and without ST-segment elevation. Investigators randomly assigned participants to receive, in addition to aspirin, either ticagrelor (180mg loading dose, followed by 90mg twice daily) or clopidogrel (300-600mg loading dose, followed by 75mg daily).

During the 12-month follow-up period, patients on ticagrelor were 16% less likely than patients on clopidogrel to experience a major cardiovascular event. Importantly, the overall rates of major bleeding were similar in the two groups, although ticagrelor did seem to increase the risk of non-procedure-related major bleeding.

"These data show that this new drug has the potential to save many lives in the UK," says Robert Storey, UK lead investigator for PLATO and Senior Lecturer & Honorary Consultant in Cardiology at the University of Sheffield and Sheffield Teaching Hospitals NHS Foundation Trust. "The results of this trial are hugely exciting in that we see, for the first time, improved efficacy without an increased overall risk of life-threatening or fatal bleeding."

A regulatory filing for ticagrelor is expected in the fourth quarter of 2009.

REFERENCES

1. Wallentin L et al. N Engl J Med 2009: 361; 1045-57.

Further information: AstraZeneca