Chapter 21 Marini Acute Coronary Syndromes

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SECTION II • Medical and Surgical Crises

Ticagrelor is a relatively reversible agent, whereas the effects of both clopidogrel and prasugrel linger for days. Although potency is an advantage of pra- sugrel, it comes at the cost of higher incidence of bleeding complications. Although their ultimate place is as yet undetermined, these newer agents reduce the incidence of stent thrombosis and have been trial-determined to reduce the likelihood of recurrent ischemic events. They may be a good option for those who present with stent thrombosis with clopidogrel, in those with multiple drug-elut- ing stents, and in those at less risk of bleeding (like the younger patient population). Glycoprotein 2b/3a Receptor Inhibitors Gp2b/3a receptor inhibitor agents are the most powerful intravenous form of antiplatelet agents available. The Gp2b/3a receptor binds to fibrino- gen, which actually forms the molecular link that bridges adjacent platelets in the process of plate- let aggregation. By binding to the Gp2b/3a recep- tors, these agents inhibit binding of fibrinogen to this receptor and thus inhibit platelet aggregation. Although the use of these agents in ACS manage- ment had surged in prior years, their use presently is more restricted, as precatheterization treatment with dual antiplatelet therapies has become more common and bivalirudin now displaces heparin as an antithrombotic in the catheterization labora- tory. There are two broad classes of these agents: (1) large-molecule agents like abciximab (ReoPro) and (2) small-molecule agents (peptide-like eptifi- batide [Integrilin] and non–peptide-like tirofiban [Aggrastat]). Because abciximab molecules bind irreversibly to the Gp2b/3a receptor and produce permanent noncompetitive platelet inhibition, the clinical effects of the medication can last for 7 to 10 days. Severe uncontrolled bleeding associated with abciximab should be addressed by stopping the medication and transfusing platelets. The small- molecule agents bind reversibly to the Gp2b/3a receptor to produce competitive platelet inhibition. The antiplatelet effects usually reverse within 4 to 6 hours of stopping the medication. Platelet trans- fusions should not be given for bleeding provoked by small-molecule Gp2b/3a receptor antagonists, as transfusion inhibits new platelet formation. The risk of major bleeding with Gp2b/3a recep- tor antagonists is 2.5% to 4.0%. Most of the bleed- ing experienced from these agents is from vascular

access sites after PCI. Severe thrombocytopenia with counts less than 50,000/mm 3 occurs in 0.5% to 1.5% of patients who receive abciximab. Because thrombocytopenia can develop within hours of initiating an abciximab infusion, it is prudent to check platelet counts within 4 hours of starting the infusion and again at the end of the infusion. Severe thrombocytopenia is rare with small-mol- ecule agents (tirofiban and eptifibatide). There is also a small chance (0.5% to 1.0%) of develop- ing serious pulmonary hemorrhage with abciximab therapy. This potentially fatal condition is rarely if ever encountered with the small molecular weight Gp2b/3a receptor antagonists. Catheterization lab- oratory practices currently favor the use of bivali- rudin (a direct thrombin inhibitor [DTI]) over the customary heparin plus GP2b/3a inhibitor strategy during the procedure and immediate postprocedure phases. Although of equivalent efficacy to the lat- ter combination, bivalirudin has been demonstrated in large clinical trials to be associated with lower bleeding risk. High cost may be a factor that limits its use in some environments. Adequate doses of intravenous heparin given urgently along with oral aspirin reduce mortality and morbidity in patients with ACS by immedi- ately interrupting the process of clotting on the coronary endothelium. The combination of hepa- rin and aspirin is superior to aspirin alone in pre- venting the early complications of UA. Superiority of the combination probably results from the dif- ferent mechanisms of the two treatments: heparin inhibits soluble clotting factors and thrombin- mediated platelet aggregation, whereas aspirin inhibits COX-mediated platelet aggregation. Even though the addition of heparin to aspirin raises the bleeding incidence slightly, the risk–benefit ratio almost always favors combination therapy. The goal of heparin therapy is to rapidly achieve and maintain a partial thromboplastin time (PTT) of 1.5 to 2.0 times the patient’s baseline or labo- ratory control value. This goal is best achieved using an intravenous bolus (60 units/kg, with a maximum dose of 4,000 units), followed by a con- tinuous intravenous heparin infusion at a rate of 12 units/kg/h (maximum 1,000 units/h). The hep- arin infusion should be continued until coronary Antithrombotic Therapy Unfractionated Heparin