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The method of this invention can be used for patients in need of antiplatelet therapy or at risk of thrombosis. The method can further be used in patients who were previously treated with long-acting platelet inhibitors without increasing the risk of excessive bleeding.
Each of the above-referenced applications is incorporated herein by reference. Currently, the approved antiplatelet products include aspirin and thienopyridines, such as clopidogrel and ticlopidine.
In the normal state, when blood vessels are damaged, platelet activation mediated by P2Yi2 receptors play an important role to arrest bleeding at the site of injury.
In a diseased state, platelet activation leads to vascular occlusion and ischemic damage. Thus, P2Yi2 receptor antagonists play a key role in antiplatelet therapy in assisting to prevent coronary artery disease and for the immediate treatment of ACS and percutaneous coronary intervention PCI.
Pending further examinations, these patients may continue with this treatment or receive other treatments such as coronary artery bypass grafting CABG and PCI. Similarly, patients who have received a bare metal stent or drug-eluting stent are also put on the dual clopidogrel and aspirin therapy for an extended period of time to prevent an ischemic event.
For instance, a post hoc analysis of a blinded, placebo-controlled trial suggests a benefit of platelet activity inhibition in terms of decreased thrombotic events prior to CABG Fox KA et. For many patients, this dual antiplatelet therapy provides tremendous clinical benefits, and minimizes the risks of ischemic events, such as heart attack and stroke.
Cessation of clopidogrel may increase the incidence of ischemic events in the short-term due to a "rebound" effect of platelet activation Brilakis ES et al, J Am Coll Cardiol. Because aspirin and thienopyridines are irreversible, long-acting platelet antagonists, reversal of the inhibition of platelet Fibrinolytic vs.
pci therapy grant proposal essay occurs only as new platelets are generated; therefore, even after discontinuation, their effect can last several days before being completely eliminated. Hence, patients are often required to stop dual antiplatelet therapy and wait for five to seven days before any invasive procedures can be performed.
As a result, physicians often face the difficult choice of discontinuing clopidogrel and aspirin prior to surgery and risking a potential ischemic event in the unprotected perioperative period or delaying surgery until the time at which clopidogrel is no longer required.
Potentially, effective platelet inhibition with an ultra short-acting platelet inhibitor during the period of clopidogrel withdrawal may protect patients from ischemic events and also preserve normal hemostasis at the time of surgery.
This new therapy should maintain platelet inhibition at acceptable levels while allowing for rapid restoration of platelet function after discontinuation, thereby "bridging" patients to their surgical procedures without increasing the risk of bleeding complications.
The reversible, short-acting P2Yi2 inhibitor can be administered to a patient as a bolus and or a continuous intravenous infusion. These methods may comprise 1 administering a bridge dosing regimen, wherein the bridge dosing regimen comprises administering intravenously a continuous infusion of cangrelor at an infusion rate of 0.
In another embodiment, the method may comprise 1 administering a bridge dosing regimen, wherein the bridge dosing regimen comprises administering intravenously a continuous infusion of cangrelor at an infusion rate of 0. However, because such elements and steps are well known in the art, and because they do not facilitate a better understanding of the present invention, a discussion of such elements and steps is not provided herein.
The disclosure herein is directed to all such variations and modifications to such elements and methods known to those skilled in the art. Furthermore, the embodiments identified and illustrated herein are for exemplary purposes only, and are not meant to be exclusive or limited in their description of the present invention.
Preferably the described methods can be used in patients at risk of thrombotic events. More preferably the embodiments of the present invention are directed to patients diagnosed with symptoms of stable or unstable angina, vascular ischemic events, atherosclerosis, acute coronary syndrome, as well as STEMI or N- STEMI.
The described methods can also be used for patients having previously received a stent, such as a bare metal stent or a drug-eluting stent, for the treatment or prevention of stent thrombosis. While the present invention is generally targeted for use with human patients, the described methods can be used on any living animal.
Examples of long-acting P2Yi2 inhibitors are typically formulated as oral dosage forms. One example of long- acting P2Yi2 inhibitor is long-acting irreversible P2Yi2 inhibitors. Examples of long- acting irreversible P2Yi2 inhibitors include thienopyridines.
Examples of thienopyridines include, without limitation, clopidogrel, ticloridine, and prasugrel and such other compounds having similar properties. Clopidogrel is a pro-drug that requires metabolism for conversion to the active metabolite.
Examples of a short-acting, reversible P2Yi2 inhibitor include, without limitations, cangrelor, ticagrelor and PRT It should be noted that the present invention is not limited to these examples.
Additional compounds that have similar properties may also be used in the present invention. Cangrelor is a potent, direct, and reversible antagonist of the platelet P2Yi2 receptor.
Cangrelor has a half-life of approximately less than 10 minutes, allowing for a return to normal platelet function in a very short period of time upon discontinuation of the drug.
By reducing the need for a compound to be metabolized for activity, and by having a relatively short half-life, reversible, short-acting P2Yi2 inhibitors are considered "reversible," meaning that full platelet functionality may return rather quickly as compared to thienopyridines.
Cangrelor can be derived completely from synthetic materials, and is an analogue of adenosine triphosphate ATP. ATP is a natural antagonist of the P2Yi2 receptor sites and is found in humans. Formula I  Cangrelor is clinically well tolerated and safe and has no drug-drug interaction with aspirin, heparin or nitroglycerin.
Unlike orally dosed thienopyridines, cangrelor can be administered intravenously and binds directly to P2Yi2 receptor sites of platelets. In each of the embodiments of the present invention, the term "cangrelor" encompasses the compound of Formula I as well as tautomeric, enantiomeric and diastereomeric forms thereof, and racemic mixtures thereof, other chemically active forms thereof, and pharmaceutically acceptable salts of these compounds, including a tetrasodium salt.
These alternative forms and salts, processes for their production, and pharmaceutical compositions comprising them, are well known in the art and set forth, for example, in U.IMS Health and Quintiles are now IQVIA. We are committed to providing solutions that enable healthcare companies to innovate with confidence, maximize opportunities and, ultimately, drive healthcare forward.
We do this via breakthroughs in insights, technology, analytics and human intelligence that bring the advances in data science together with the possibilities of human science. l Fibrinolytic vs.
PCI therapy Grant Proposal Francesca Tierney UWF, College of Letters and Sciences, Biology Department, SAHLS Health Science Research Seminar, HSC James Hunt 11/16/ Executive Summary Fibrinolytic therapy has been a significant means of establishing reperfusion in patients whom have had a myocardial infarction or.
OneOC E. 4th Street, Suite Santa Ana, CA Formerly Volunteer Center Orange County attheheels.com CDBG Grant Proposal Sample Family Service . The University of Otago provides a research-led learning environment that is second-to-none, with a richly-deserved reputation for excellence.
Fibrinolytic Vs. PCI Therapy Grant Proposal. Filed Under: Essays. The proposed research will be a randomized controlled clinical trial study that will explore the roles of Fibrinolytic therapy vs. PCI in patients whom have received one of the two-reperfusion therapies, and examine the effects of each and symptoms caused.
The Essay on. Percutaneous coronary intervention in patients receiving enoxaparin or unfractionated heparin after fibrinolytic therapy for ST-segment elevation myocardial infarction in the ExTRACT-TIMI 25 trial.
J Am Coll Cardiol. ;49(23)