ST Elevation Myocardial Infarction Thienopyridine Therapy
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Thienopyridines
Mechanism of Benefit Currently there are two agents in this class, Ticlopidine and clopidogrel. Prasugrel is currently an investigational drug in this class. These agents inhibit the ADP-receptor and thereby reduce platelet activation.
Clinical Trial Data
While the combination of clopidogrel with fibrinolytic agents is not part of the current ACC / AHA guidelines, clinical trial data from the CLARITY study did demonstrate imporved patency associated with their combination, with no increase in the risk of intracranial hemmorhage. The combination of clopidogrel combined with aspirin has been associated with a reduced risk of stent thrombosis following coronary stent implantation (576-580). Among patients with aspirin sensitivity where aspirin is contraindicated, clopidogrel may reduce the risk of reocclusion (581). The ACC / AHA guidelines do not recommend routine administration of clopidogrel as pretreatment "in patients who have not yet undergone diagnostic cardiac catheterization and in whom CABG surgery would be performed within 5 to 7 days if warranted (431)."
Dosing
Data from the non-ST elevation MI population does demonstrate that a 600 mg oral dose achieves sustained inhibition more rapidly than a 300 mg dose. A 600 mg dose does not, however, achieve a higher level of inhibition. The FDA package insert loading dose is 300 mg, but in clinical practice both 300 and 600 mg doses are used.
Side Effects
Ticlopidine administration has been associated with neutropenia and thrombotic thrombocytopenia (TTP). It is as a result of these potential side effects that clopidogrel is often prescribed instead. Clopidogrel may also be preferred because of the lack of need for laboratory monitoring, and once-daily dosing. It should be noted, however, that approximately one third to one quarter of patients may be resistant to clopidogrel, which is a pro-drug. For those patients who develop stent thrombosis while on clopidogrel, ticlopidine may be an optimal substitution because it is not a pro-drug and is not metabolized by the same pathway as clopidogrel.
Guidelines (DO NOT EDIT)
- Class I
1. In patients who have undergone diagnostic cardiac catheterization and for whom PCI is planned, clopidogrel should be started and continued for at least 1 month after bare metal stent implantation, for several months after drug-eluting stent implantation (3 months for sirolimus, 6 months for paclitaxel), and up to 12 months in patients who are not at high risk for bleeding. (Level of Evidence: B)
2. In patients taking clopidogrel in whom CABG is planned, the drug should be withheld for at least 5 days, and preferably for 7 days, unless the urgency for revascularization outweighs the risks of excess bleeding. (Level of Evidence: B)
- Class IIa
Clopidogrel is probably indicated in patients receiving fibrinolytic therapy who are unable to take aspirin because of hypersensitivity or major gastrointestinal intolerance. (Level of Evidence: C)
References
Acknowledgement and Attribution Regarding Sources of Content
Some of the initial content on this page may be incorporated in part from copyleft sources in the public domain including wikis such as Wikipedia and AskDrWiki. Drug information for patients came from the The National Library of Medicine. Infectious disease information may have come from the Centers for Disease Control (CDC). Differential Diagnoses are drawn from clinicians as well as an amalgamation of 3 sources: 1.The Disease Database; 2. Kahan, Scott, Smith, Ellen G. In A Page: Signs and Symptoms. Malden, Massachusetts: Blackwell Publishing, 2004:3; 3. Sailer, Christian, Wasner, Susanne. Differential Diagnosis Pocket. Hermosa Beach, CA: Borm Bruckmeir Publishing LLC, 2002:7 .
