[Antithrombin therapy in acute coronary syndromes].
Intracoronary thrombosis is fundamental in the pathogenesis of acute coronary syndromes, although the causes of thrombosis are still unclear. As thrombin generation is crucial for thrombus formation, the inhibition of thrombin is a primary aim to prevent the evolution of an initial repair process into a pathological thrombus. Thrombin inhibition can be achieved by several drugs. Heparin is the principal antithrombin drug currently used in acute syndromes; it acts mainly by binding to antithrombin III and increasing its inhibitory effect on thrombin and other coagulation factors. The heparin-antithrombin III complex, however, does not inhibit thrombus-bound thrombin; moreover, iv heparin requires frequent laboratory monitoring and dose adjustments. Despite these limitations, continuous infusion of i.v. heparin has been found to be effective in unstable angina and in myocardial infarction, especially when treated with accelerated rt-PA. New antithrombin drugs that selectively and directly inhibit thrombin are hirudin, its synthetic derivate hirulog, and argatroban. These drugs have several theoretical advantages over heparin: greater stability of the aPTT--with the need for less laboratory monitoring--and greater efficacy--associated mainly with its capacity to inhibit clot-bound thrombin. Clinical pilot studies seem to indicate a greater antithrombotic efficacy compared with heparin, but a greater number of hemorrhagic events in patients with acute myocardial infarction receiving thrombolysis. In conclusion, the use of heparin is certainly indicated in patients with unstable angina and persistent ischemia and in acute myocardial infarction treated with accelerated rt-PA. The use of new antithrombin drugs, although promising, requires further clinical evaluation.
Maseri
A
A
Istituto di Cardiologia, Università Cattolica del Sacro Cuore, Roma.
Andreotti
F
F
Biasucci
L M
LM
Rebuzzi
A G
AG
D000208:Acute Disease; D000789:Angina, Unstable / Q000209:etiology / Q000517:prevention & control; D003328:Coronary Thrombosis / Q000150:complications / Q000188:drug therapy*; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D006493:Heparin / Q000627:therapeutic use; D006801:Humans; D009203:Myocardial Infarction / Q000209:etiology / Q000517:prevention & control; D013577:Syndrome; D013917:Thrombin / Q000037:antagonists & inhibitors; D015912:Thrombolytic Therapy; D014812:Vitamin K / Q000037:antagonists & inhibitors
D005343:Fibrinolytic Agents; D014812:Vitamin K; D006493:Heparin; D013917:Thrombin
Terapia antitrombinica nelle sindromi coronariche acute.