September 28, 2009 – New data from the phase III PLATO study showed that ticagrelor (BRILINTA) provided 16 percent reduction of cardiovascular (CV) events (composite of CV death, heart attack and stroke) than clopidogrel (9.02 vs. 10.65 percent) in acute coronary syndromes patients undergoing planned invasive treatment of either PCI or CABG.
Although patients undergoing invasive procedures are at greater risk of bleeding, these results were achieved without a significant increase in major bleeding compared to clopidogrel (11.5 vs. 11.6 percent). Patients with planned invasive procedures at randomization accounted for more than 70 percent of the greater than 18,000 patients in PLATO. These sub-analysis data were presented today at the Transcatheter Cardiovascular Therapeutics (TCT) conference in San Francisco.
Additional findings from this PLATO invasive sub-analysis 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 (e.g. 600 mg) was given. Specifically, results in this subgroup analysis indicated treatment with ticagrelor:
• Reduced CV death 3.4 vs. 4.3 percent, relative risk reduction of 18 percent.
• Reduced myocardial infarction (heart attack, MI) 5.3 vs. 6.6 percent, a relative risk reduction of 20 percent.
• Reduced definite stent thrombosis 1 vs. 1.6 percent, a relative risk reduction of 38 percent.
• Reduced total mortality 3.9 vs. 5.1 percent, a relative risk reduction of 19 percent.
"The majority of patients rushed to the hospital with severe chest pain or heart attacks will have an invasive procedure," said Christopher Cannon, M.D., PLATO Executive Committee member, a cardiologist at Brigham and Women's Hospital in Boston. "Doctors need to make quick decisions about antiplatelet therapy for patients who are sent for cardiac catheterization and may need angioplasty or surgery. In this study population, ticagrelor led to fewer heart attacks and deaths without a significant increase in major bleeding versus clopidogrel."
Similar to the overall PLATO findings, Dyspnoea (shortness of breath) was more common among patients on ticagrelor but less than 1 percent discontinued ticagrelor treatment in the sub-analysis because of dyspnoea.
The PLATO study was designed to reflect how patients with ACS are currently managed in clinical practice, by including patients who underwent invasive procedures and those who were managed with medication only.
Last month, the primary results from PLATO were presented at the European Society of Cardiology and simultaneously published in The New England Journal of Medicine in August 2009.
AstraZeneca remains on track to submit BRILINTA to regulatory authorities in the fourth quarter of this year.
PLATO (A Study of PLATelet Inhibition and Patient Outcomes) was a head-to-head 18,624 patient outcomes study of ticagrelor plus aspirin versus the active comparator, clopidogrel plus aspirin, and was designed to establish whether ticagrelor could achieve meaningful cardiovascular and safety endpoints in ACS patients, above and beyond those afforded by clopidogrel, an irreversible therapy in the thienopyridine class of medicines. The study design of PLATO was published in the April 2009 edition of the American Heart Journal.
Ticagrelor (BRILINTA) is an investigational oral anti-platelet treatment for ACS. BRILINTA (ticagrelor) is a reversibly binding oral adenosine diphosphate (ADP) receptor antagonist. It selectively inhibits P2Y(12), a key target receptor for ADP. ADP receptor blockade inhibits the action of platelets in the blood, reducing recurrent thrombotic events.
BRILINTA is the first in a new chemical class, the CPTPs (cyclo-pentyl-triazolo-pyrimidines) and is chemically distinct from the thienopyridines, such as clopidogrel and prasugrel.
AstraZeneca has proposed the name BRILINTA in the United States. If approved by the FDA it will serve as the trade name for ticagrelor. BRILINTA is a trademark of the AstraZeneca group of companies.
For more information: www.astrazeneca-us.com