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Ticagrelor: an investigational oral antiplatelet treatment for reduction of major adverse cardiac events in patients with acute coronary syndrome Abergel E; Nikolsky EVasc Health Risk Manag 2010[Oct]; 6 (ä): 963-77Acute coronary syndromes (ACS) are the leading cause of mortality and one of the main reasons for hospital admissions in the developed nations. Due to high rates of mortality and reinfarction, ACS represent a major public health concern. Platelets play a central role in atherothrombosis, the main pathologic substrate in ACS. Sufficient inhibition of platelet aggregation is therefore one of the key targets in the treatment of ACS. Blockade of the P2Y12 subtype of adenosine diphosphate (ADP) receptor on platelet cell membranes has been established as a key mechanism of platelet inhibition. Clopidogrel, an ADP receptor antagonist and a second-generation thienopyridine, has been demonstrated to be of clinical benefit in patients with ACS when added to aspirin. A delayed onset of action due to two-step conversion to the active metabolite, irreversible binding to P2Y12 receptors, and broad interindividual variability in levels of platelet response are the main limitations of clopidogrel. Prasugrel, a novel third-generation thienopyridine, provides faster and stronger inhibition of platelet aggregation than clopigodrel. However, like the active metabolite of clopidogrel, prasugrel binds irreversibly to the P2Y12 ADP receptor site, causing inhibition of platelet aggregation for the life of the platelet. Although in a randomized, double-blind trial prasugrel demonstrated superiority for multiple cardiovascular endpoints compared with standard-dose clopidogrel, it was also associated with an increased bleeding risk, including fatal bleeding. This review discusses the optimal antiplatelet regimens for management of patients with ACS, with special focus on ticagrelor, the first oral agent in a new chemical class of nonthienopyridine antiplatelet agents termed cyclopentyltriazolo-pyrimidines. Faster and greater platelet inhibition than clopidogrel, quick recovery of platelet function, and high efficacy regardless of clopidogrel response status, are the obvious advantages of ticagrelor as compared with thienopyridines. The prospective, randomized Platelet Inhibition and Patient Outcomes trial has established the clinical utility, enhanced efficacy, and similar safety of ticagrelor as compared with clopidogrel in a wide range of patients with ACS managed with contemporary antithrombotic therapies and invasive strategies when indicated. Dyspnea, ventricular pauses >/=3 seconds, and elevation of serum creatinine and uric acid are the most common known adverse effects associated with ticagrelor, and require further comprehensive assessment.|Acute Coronary Syndrome/complications/*drug therapy[MESH]|Adenosine/adverse effects/*analogs & derivatives/therapeutic use[MESH]|Aspirin/therapeutic use[MESH]|Blood Platelets/drug effects[MESH]|Clopidogrel[MESH]|Dyspnea/chemically induced[MESH]|Humans[MESH]|Platelet Aggregation Inhibitors/adverse effects/*therapeutic use[MESH]|Randomized Controlled Trials as Topic[MESH]|Receptors, Purinergic P2Y12/drug effects[MESH]|Ticagrelor[MESH]|Ticlopidine/analogs & derivatives/therapeutic use[MESH]|Treatment Outcome[MESH] |
