PLATO Subanalysis of AstraZeneca's Ticagrelor Presented at TCT

September 24, 2009—AstraZeneca PLC (Wilmington, DE) announced that new data from the phase 3 PLATO (Platelet Inhibition and Patient Outcomes) study showed that ticagrelor, the company's investigational oral antiplatelet treatment for acute coronary syndrome, provided greater reduction of cardiovascular events (composite of cardiovascular death, myocardial infarction, and stroke) than clopidogrel (9.02% vs 10.65%; P = .0025; relative risk reduction = 16%) in acute coronary syndrome patients undergoing planned invasive treatment (either percutaneous coronary intervention or coronary artery bypass graft surgery). Although patients undergoing invasive procedures are at a greater risk of bleeding, these results were achieved without a significant increase in major bleeding compared to clopidogrel (11.5% vs 11.6%; P = .88). Patients with planned invasive procedures at randomization accounted for greater than 70% of the more than 18,000 patients in PLATO, the company stated.

These subanalysis data were presented at the Transcatheter Cardiovascular Therapeutics (TCT) 2009 scientific symposium in San Francisco. The primary results from PLATO were presented in September at the European Society of Cardiology Congress meeting and simultaneously published by Lars Wallentin, MD, et al in the New England Journal of Medicine (2009;361:1045-1057). The PLATO study was designed to reflect how patients with acute coronary syndrome are currently managed in clinical practice, by including patients who underwent invasive procedures and those who were managed with medication only.

According to AstraZeneca, additional findings from this PLATO invasive subanalysis showed that treatment with ticagrelor, compared to clopidogrel, demonstrated an effect consistent with the results for the entire invasive subgroup across the multiple secondary efficacy endpoints. The effect was seen regardless of whether a standard 300-mg loading dose of clopidogrel was given or an additional loading dose of clopidogrel (eg, 600 mg) was given. Subgroup analysis results indicated treatment with ticagrelor:

• Reduced cardiovascular death (3.4% vs 4.3%; P = .025; relative risk reduction = 18%).
• Reduced myocardial infarction (5.3% vs 6.6%; P = .002; relative risk reduction = 20%).
• Reduced definite stent thrombosis (1% vs 1.6%; P = .003; relative risk reduction = 38%).
• Reduced total mortality (3.9% vs 5.1%; P = .01; relative risk reduction = 19%).

Similar to the overall PLATO findings, dyspnea was more common among patients on ticagrelor, but less than 1% discontinued ticagrelor treatment in the subanalysis because of dyspnea.

Brilinta is the company's proposed tradename for ticagrelor. AstraZeneca stated that it expects to submit Brilinta to regulatory authorities in the fourth quarter of this year.