Paul A. Gurbel

Prasugrel 5mg in the very elderly is non-inferior to prasugrel 10mg in non-elderly patients : the generations trial, a pharmacodynamic (PD) study in stable CAD patients

The p110alpha subunit of PI 3-kinase is crucially involved in neointima formation by mediating smooth muscle cell proliferation, migration and survivalRadiation exposure during electrophysiology procedures : results from the EPIC global survey

Percutaneous Coronary Intervention: Adjunctive Pharmacology

Percutaneous coronary intervention (PCI) promotes thrombosis by inducing extreme vascular injury. The concomitant presence of dysfunctional endothelium, vulnerable plaque, and endothelial erosion promotes further thrombotic risk. Platelet adhesion to newly exposed collagen and von Willebrand factor by specific receptors and binding of thrombin generated by tissue factor to protease-activated receptors (PARs) cause initial platelet activation. Following activation, adenosine diphosphate (ADP) is released from dense granules and thromboxane A2 is generated by cyclooxygenase-1 (COX-1). Although both thromboxane A2 and ADP amplify platelet activation and aggregation, continuous ADP-P2Y12 receptor signaling is essential for sustained activation of the GPIIb/IIIa receptor and stable thrombus generation. Simultaneously, platelet activation exposes the phosphatidylserine surface providing binding sites for coagulation factors and the generation of thrombin. Thrombin converts fibrinogen to fibrin and activates factor XIII that cross-links the fibrin network, stabilizes the platelet-fibrin clot at the site of vascular injury, and impairs myocardial blood supply. Therefore, the rationale for antithrombotic therapy during and following PCI is to prevent thrombus formation within the target lesion and also in nontarget vessels by attenuating platelet activation and aggregation and arresting coagulation processes. Since clot formation involves multiple pathways including platelet activation and aggregation and coagulation, simultaneous blockade of these pathways is essential to prevent periprocedural and post-PCI ischemic event occurrences. Optimal inhibition of these pathways is essential for maximizing antithrombotic effects and minimizing bleeding risk and is critically dependent on individual patient risk.

HDL3: A MARKER OF CORONARY ARTERY DISEASE SEVERITY AND INFLAMMATION IN PATIENTS ON STATIN THERAPY

Background: High-density lipoprotein (HDL) and inflammation are risk factors for coronary artery disease (CAD). There are very limited data evaluating the role of HDL sub-particles HDL2 and HDL3 for assessing severity of CAD in patients on statin and 325mg/day aspirin therapy. We aim to identify if

Vascular risk levels affect predictive value of platelet reactivity for the occurrence of MACE in clopidogrel treatment

Prior studies have shown an association between high on-clopidogrel platelet reactivity (PR) and the risk of major adverse cardiovascular events (MACE). However, large intervention trials on PR-tailored treatments have been neutral. The role and usefulness of PR with regard to levels of cardiovascular risk are unclear. We undertook a systematic review and meta-analysis of individual patient data on MACE outcomes (acute coronary syndromes (ACS), ischaemic strokes, and vascular deaths) in relation to PR and its interaction with cardiovascular risk levels. PR was determined using ADP-induced light transmission aggregometry with a primary concentration of 20 µM ADP. Thirteen prospective studies totaled 6,478 clopidogrel-treated patients who experienced 421 MACE (6.5 %) during a median follow-up of 12 months. The strength of the association between the risk of MACE and PR increased significantly (p=0.04) with the number of risk factors present (age> 75 years, ACS at inclusion, diabetes, and hypertension). No association was detected in patients with no risk factor (p=0.48). In patients presenting one risk factor, only high-PR was associated with an increased risk of MACE (HR 3.2, p=0.001). In patients presenting ≥ 2 risk factors, the increase of risk started from medium-PR (medium-PR: HR=2.9, p=0.0004; high-PR: HR=3.7, p=0.0003). PR allowed the reclassification of 44 % of the total population to a different risk level for the outcome of MACE, mostly in intermediate or high risk patients. In conclusion, the magnitude of the association between PR and MACE risk is strongly dependent on the level of cardiovascular risk faced by patients on clopidogrel.