Friday, 25 September 2009
New data from the phase III PLATO study showed that BRILINTA (ticagrelor) provided greater reduction of cardiovascular (CV) events (composite of CV death, heart attack and stroke) than clopidogrel (9.02% vs. 10.65%, p=0.0025 a 16% Relative Risk Reduction) in acute coronary syndromes patients undergoing planned invasive treatment (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%, p=0.88). Patients with planned invasive procedures at randomisation accounted for more than 70% 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 BRILINTA, compared to clopidogrel, demonstrated an effect consistent with the results for the entire PLATO population 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 sub-group analysis indicated treatment with ticagrelor:
- Reduced CV death 3.4% vs. 4.3% (p=0.025) Relative Risk Reduction of 18%
- Reduced myocardial infarction (heart attack, MI) 5.3% vs. 6.6% (p=0.002)
- Relative Risk Reduction of 20%
- Reduced definite stent thrombosis 1.0% vs. 1.6% (p=0.003) Relative Risk Reduction of 38%
- Reduced total mortality 3.9% vs. 5.1% (p=0.01) Relative Risk Reduction of 19%
"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 catheterisation 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% 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.
The bleeding definitions used within the PLATO trial were an evolution from the CURE bleeding definitions and were developed by the PLATO Executive Committee as constituting the most appropriate and clinically meaningful assessment of bleeding complications associated with acute and chronic therapy. The PLATO bleeding definitions provide a framework to allow investigators to record all bleeding events reported by patients in the PLATO trial. The bleeding definitions were developed to characterise bleeding in both the acute and long-term setting.
Given the size of the PLATO database, AstraZeneca will continue to analyse and publish additional PLATO findings.
NOTES TO EDITORS:
Ticagrelor (BRILINTA™) is an investigational oral antiplatelet treatment for ACS. BRILINTA (ticagrelor) is a reversibly binding oral adenosine diphosphate (ADP) receptor antagonist. It selectively inhibits P2Y12, 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 BRILINTATM in the US. If approved by the FDA it will serve as the trade name for ticagrelor. BRILINTA is a trademark of the AstraZeneca group of companies.
*About Invasive Strategies for Acute Coronary Syndromes
Percutaneous coronary intervention (PCI) is a procedure to open existing blocked arteries, also known as angioplasty. Coronary artery bypass graft (CABG) is a procedure where surgeons bypass the affected artery in the heart.
AstraZeneca is a major international healthcare business engaged in the research, development, manufacturing and marketing of meaningful prescription medicines and supplier for healthcare services. AstraZeneca is one of the world's leading pharmaceutical companies with healthcare sales of US$ 31.6 billion and is a leader in gastrointestinal, cardiovascular, neuroscience, respiratory, oncology and infectious disease medicines. For more information about AstraZeneca, please visit: www.astrazeneca.com
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