Blockers of Platelet Aggregation

During platelet aggregation, fibrinogen forms a bridge between adjacent platelets by binding to the platelet-surface receptor, glycoprotein IIb-IIIa. A variety of agents that interfere with the platelet membrane and the glycoprotein IIb-IIIa receptor have been introduced into clinical practice during the past few years.

PLATELET MEMBRANE ALTERING AGENTS Ticlopidine and clopidogrel deform the region of the platelet membrane next to its fibrinogen receptor and render it ineffective. Both of these agents have little utility in the acute setting. Ticlopidine (250 mg twice daily) improves outcomes in unstable angina but has a 24- to 28-h delay in its onset of action and is associated with reversible neutropenia. Ticlopidine is currently approved for use in patients with cerebrovascular diseases for whom aspirin therapy fails or who are aspirin-intolerant or allergic. 16 Clopidogrel (75 mg per day), a similar agent, has been approved for secondary prevention of AMI and CVA and in established peripheral artery disease. Its side effects include gastrointestinal upset and possible interactions with other medications. 17

GLYCOPROTEIN IIB-IIIA RECEPTOR INHIBITORS Abciximab, eptifibatide, and tirofiban, glycoprotein IIb-IIIa receptor inhibitors, have been studied in AMI, unstable angina, and high-risk patients undergoing percutaneous angioplasty (PCTA).18 Benefit has been consistently found when these agents are used in combination with other antithrombotic (aspirin, ticlodipine, or heparin) and reperfusion (fibrinolytics or PCTA) therapy. 1 ,19 Patients receiving glycoprotein IIb-IIIa inhibitors are more likely to have bleeding complications (particularly if heparin is also used and usually related to catheterization or coronary artery bypass surgery) but have no increased risk of intracranial hemorrhage. However, there is no clear evidence that glycoprotein IIb-IIIa inhibitors need to be started in the emergency department, as opposed to waiting until the patient reaches the catheterization laboratory or coronary care unit. 20

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