NEW YORK (Reuters Health) – In patients with acute coronary syndromes (ACS), ticagrelor appears to be more effective than clopidogrel in reducing the incidence of death from vascular causes, myocardial infarction, or stroke, without increasing the overall rate of major bleeding. These findings are derived from the Study of Platelet Inhibition and Patient Outcomes (PLATO), a multinational, double-blind, randomized trial published in an Online First issue of the New England Journal of Medicine. “Ticagrelor is an oral, reversible, direct-acting inhibitor of the adenosine diphosphate receptor P2Y12 that has a more rapid onset and more pronounced platelet inhibition than clopidogrel,” lead author Dr. Lars Wallentin, from University Hospital in Uppsala, Sweden, and co-investigators explain.

PLATO included 18,624 patients from 862 centers in 43 countries hospitalized for ACS, with or without ST-segment elevation, between 2006 and 2008. According to the report, 9333 patients were assigned to treatment with ticagrelor, 180 mg as a loading dose followed by 90 mg twice daily, and 9291 were assigned to receive clopidogrel, 300-600 mg as a loading dose and then 75 mg per day. Follow-up continued to February 2009; the median duration of exposure to the study drug was 277 days.

The primary endpoint – a composite of death from vascular causes, myocardial infarction or stroke – occurred in 9.8% of patients in the ticagrelor group and in 11.7% in the clopidogrel group (hazard ratio 0.84, p < 0.001). Ticagrelor was also associated with lower mortality from any cause, both overall (4.5% vs 5.9%, p < 0.001) and among the subset of patients for whom invasive treatment was planned (8.9% vs 10.6%, p = 0.003).

Although there was no difference between groups in rates of major bleeding, ticagrelor was associated with a higher rate of non-procedure-related bleeding. More patients discontinued the study drug due to adverse effects in the ticagrelor group (7.4% vs 6.0%, p < 0.001).

“The availability of three agents for antagonizing platelet ADP receptors” — ticagrelor, clopidogrel, and prasugrel – “may make it possible to individualize antiplatelet therapy,” Dr. Albert Schomig, from the Deutsches Herzzentrum and First Medizinische Klinik rechts der Isar in Munich, Germany, writes in a related editorial.

He suggests that “ticagrelor therapy may be preferred in patients whose coronary anatomy is unknown and for whom a CABG procedure is deemed probable.”

He notes, however, that ticagrelor should probably be avoided in patients who have a history of stroke or a high risk of bleeding or other comorbidities.

Astra-Zeneca, sponsor of PLATO, participated in the design and oversight of the trial and coordinated data management.

Reference:
N Engl J Med 2009.