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Volume 141, Issue 2, Supplement, February 2012, Pages e89S-e119S
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Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physician Evidence-Based Clinical Practice Guidelines Online Only Articles
Antiplatelet Drugs: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines

https://doi.org/10.1378/chest.11-2293Get rights and content

The article describes the mechanisms of action, pharmacokinetics, and pharmacodynamics of aspirin, dipyridamole, cilostazol, the thienopyridines, and the glycoprotein IIb/IIIa antagonists. The relationships among dose, efficacy, and safety are discussed along with a mechanistic overview of results of randomized clinical trials. The article does not provide specific management recommendations but highlights important practical aspects of antiplatelet therapy, including optimal dosing, the variable balance between benefits and risks when antiplatelet therapies are used alone or in combination with other antiplatelet drugs in different clinical settings, and the implications of persistently high platelet reactivity despite such treatment.

Section snippets

Aspirin

Aspirin is the most widely studied antiplatelet drug. On the basis of > 100 randomized trials in high-risk patients, aspirin reduces vascular death by ∼15% and nonfatal vascular events by ∼30%.9, 10

Mechanism of Action

Dipyridamole is a pyrimidopyrimidine derivative with vasodilator and antiplatelet properties. The mechanism of action of dipyridamole as an antiplatelet agent is controversial.148 Both inhibition of cyclic nucleotide phosphodiesterase (the enzyme that degrades cyclic adenosine monophosphate [AMP] to 5-AMP, resulting in the intraplatelet accumulation of cyclic AMP, an inhibitor of platelet aggregation) and blockade of the uptake of adenosine (which binds to A2 receptors, stimulates platelet

Mechanism of Action

Cilostazol is a 2-oxoquinolone derivative that is reported to have vasodilatory and antiplatelet properties as well as antiproliferative effects, reducing smooth muscle cell proliferation and neointimal hyperplasia after endothelial injury. Cilostazol is a common cause of GI side effects, and headache occurs in up to one-fourth of patients within the first 2 weeks of starting treatment. Cilostazol is contraindicated in patients with heart failure because of the potential to trigger ventricular

Thienopyridines

Ticlopidine, clopidogrel, and prasugrel represent three generations of oral thienopyridines that selectively inhibit ADP-induced platelet aggregation. The first-generation agent ticlopidine was limited by bone marrow toxicity and has largely been replaced by clopidogrel, which has become established as standard therapy across the spectrum of patients with ACS and in those undergoing percutaneous coronary intervention (PCI). However, clopidogrel also has limitations, including variable

Glycoprotein IIb/IIIa Antagonists

The pharmacologic characteristics of the three approved IV glycoprotein IIb/IIIa (GpIIb-IIIa) inhibitors abciximab, tirofiban, and eptifibatide are summarized in Table 7.

Conclusion

Antiplatelet therapies are effective for prevention of platelet-rich arterial thrombi that form under high-shear conditions. Antiplatelet therapies are also effective for the prevention of fibrin-rich thrombi that form under low-shear conditions, such as VTE and left atrial appendage thrombi that form in patients with atrial fibrillation, but for these indications, antiplatelet drugs are less effective than anticoagulants. The efficacy of antiplatelet drugs for thrombosis prevention is

Acknowledgments

Author contributions: As Topic Editor, Dr Eikelboom oversaw the development of this article, including any analysis and subsequent development of the information contained herein.

Dr Eikelboom: contributed as Topic Editor.

Dr Hirsh: contributed as a panelist.

Dr Spencer: contributed as a panelist.

Dr Baglin: contributed as a panelist.

Dr Weitz: contributed as a panelist.

Financial/nonfinancial disclosures: In summary, the authors have reported to CHEST the following conflicts of interest: Dr

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    Funding/Support: The Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines received support from the National Heart, Lung, and Blood Institute [R13 HL104758] and Bayer Schering Pharma AG. Support in the form of educational grants was also provided by Bristol-Myers Squibb; Pfizer, Inc; Canyon Pharmaceuticals; and sanofi-aventis US.

    Disclaimer: American College of Chest Physician guidelines are intended for general information only, are not medical advice, and do not replace professional medical care and physician advice, which always should be sought for any medical condition. The complete disclaimer for this guideline can be accessed at http://chestjournal.chestpubs.org/content/141/2_suppl/1S.

    Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (http://www.chestpubs.org/site/misc/reprints.xhtml).

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