PLATE NOX Version 1
Research type
Research Study
Full title
Is efficacy of PLAtelet aggregation inhibition by Ticagrelor mediated P2Y12 blockade dependent upon endogenous Endothelial Nitric OXide?
IRAS ID
141072
Contact name
Angela Hoye
Contact email
Sponsor organisation
Hull and East Yorkshire Research and Development Department
Research summary
Acute coronary syndrome (ACS) is an umbrella term representing all diseases related to reduction in blood flow to the heart characterised by clot formation over a segment of blood vessel narrowing. This can partly exclude blood flow (unstable angina) or block the flow completely (heart attack) causing irreversible damage to the heart muscle. Treatment consists of unblocking the artery mechanically (stent or balloon therap (Percutaneous Coronary Intervention (PCI)) in combination with pharmacologically (medicines). A major constituent of clot is blood cells called platelets and many of the medications used in ACS target their function.
The National Institute for Health and Care Excellence (NICE) recommend ACS patients should be treated with two oral agents targeted in reducing platelet function, aspirin and ticagrelor. Aspirin’s mechanism of action has long since been well described, however ticagrelor is a much newer agent and recent data has suggested a new mechanism of action. Ticagrelor is known to reduce platelet activity in clot formation by blocking a specific step in the process (P2Y12 receptors). A recent study has found a possible additional pathway involving a molecule produced by the blood vessel lining called nitric oxide (NO). NO has multiple functions but is known itself to limit clot formation. There has now been found a link proposing that the presence of ticagrelor may also reduce clot formation by significantly enhancing this pathway.
This is of particular interest if translates into clinical practice, as many patients with heart disease have abnormal function of their blood vessel lining. Both of diabetics and smokers are known from research to have abnormal function of their blood vessel lining, which suggests a reduction in level of nitric oxide available. Does this therefore mean these patients will have a reduced response to ticagrelor therapy and subsequently be at increased risk of clot formation?
REC name
Yorkshire & The Humber - South Yorkshire Research Ethics Committee
REC reference
14/YH/0179
Date of REC Opinion
1 Jul 2014
REC opinion
Further Information Favourable Opinion