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Review
, 141 (2 Suppl), e89S-e119S

Antiplatelet Drugs: Antithrombotic Therapy and Prevention of Thrombosis, 9th Ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines

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Review

Antiplatelet Drugs: Antithrombotic Therapy and Prevention of Thrombosis, 9th Ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines

John W Eikelboom et al. Chest.

Abstract

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.

Figures

Figure 1.
Figure 1.
Arachidonic acid metabolism and mechanism of action of aspirin. Arachidonic acid, a 20-carbon fatty acid containing four double bonds, is liberated from the sn2 position in membrane phospholipids by several forms of phospholipase, which are activated by diverse stimuli. Arachidonic acid is converted by cytosolic prostaglandin H synthases, which have both COX and HOX activity, to the unstable intermediate prostaglandin H2. The synthases are colloquially termed “cyclooxygenases” and exist in two forms, COX-1 and COX-2. Low-dose aspirin selectively inhibits COX-1, and high-dose aspirin inhibits both COX-1 and COX-2. Prostaglandin H2 is converted by tissue-specific isomerases to multiple prostanoids. These bioactive lipids activate specific cell membrane receptors of the superfamily of G-protein-coupled receptors. COX = cyclooxygenase; DP = prostaglandin D2 receptor; EP = prostaglandin E2 receptor; FP = prostaglandin F receptor; HOX = hydroperoxidase; IP = prostacyclin receptor; TP = thromboxane receptor.
Figure 2.
Figure 2.
Maximal capacity of human platelets to synthesize TXB2, rate of TXB2 production in healthy subjects, and relationship between the inhibition of platelet cyclooxygenase activity and TXB2 biosynthesis in vivo. Left, The level of TXB2 production stimulated by endogenous thrombin during whole-blood clotting at 37°C., Center, The metabolic fate of TXA2 in vivo and the calculated rate of its production in healthy subjects on the basis of TXB2 infusions and measurement of its major urinary metabolite. Right, The nonlinear relationship between inhibition of serum TXB2 measured ex vivo and the reduction in the excretion of thromboxane metabolite measured in vivo. TXA2 = thromboxane A2; TXB2 = thromboxane B2.
Figure 3.
Figure 3.
The absolute risk of vascular complications is the major determinant of the absolute benefi t of antiplatelet prophylaxis. Data are plotted from placebo-controlled aspirin trials in different clinical settings. For each category of patients, the abscissa denotes the absolute risk of experiencing a major vascular event as recorded in the placebo arm of the trials. The absolute benefi t of antiplatelet treatment is reported on the ordinate as the number of subjects in whom an important vascular event (nonfatal MI, nonfatal stroke, or vascular death) is actually prevented by treating 1,000 subjects with aspirin for 1 year. MI 5 myocardial infarction.

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