[Therapy of acute coronary syndrome. Aspirin, heparin, low-molecular-weight heparin, hirudin and GP-IIb/IIIa blockers].
Plaque rupture with consecutive formation of an intraluminal, platelet-rich thrombus is the central mechanism leading to critical reduction of coronary perfusion in the acute coronary syndrome. Current therapeutic strategies aim at the inhibition of activation of platelets and the coagulation cascade and the suppression of platelet aggregation and fibrin formation. The use of acetylsalicylic acid (ASA) is well established in the therapy of the acute coronary syndrome and its efficacy is documented in several large clinical studies. The results of a respective metaanalysis by the Antiplatelet Trialists' Collaboration are shown in Table 1. Further risk reduction has been achieved with the additional application of heparin during the early phase of treatment. Table 2 shows the results of the Montreal Heart Study of combined vs single drug treatment, and Figure 1 a metaanalysis by Oler et al. of combination therapy with heparin plus ASA compared to monotherapy with ASA. In the past, hirudin and analogues were not superior to heparin as adjunctive treatments to lysis in acute myocardial infarction, but bleeding complications were more frequent. In contrast, in the recently published OASIS-2 study, outcome in patients with unstable angina pectoris was significantly better with hirudin than with heparin. Several large studies have demonstrated at least equivalent efficacy of LMWHs compared to standard heparin. For the early phase of the acute coronary syndrome, the FRIC and ESSENCE studies have even demonstrated improved clinical outcome without increase in bleeding complications. However, in TIMI 11 and FRAXIS, long-term application of LMWH resulted in more bleeding complications and, in FRAXIS, in a trend to a worse clinical outcome. The use of GP-IIb/IIIa blockers, especially the chimeric antibody fragment abciximab, is well established in interventional cardiology. Figure 2 shows the mechanism of action of the GP-IIb/IIIa blockers on platelet aggregation. In addition, their use in conjunction with ASA and heparin in the acute coronary syndrome led to further significant reduction of cardiovascular events in several studies. For example, the reduction of events by abciximab in the CAPTURE-study is delineated in Table 3. The results obtained with several of the new competitive GP-IIb/IIIa receptor antagonists are shown in Table 4.
Gaede
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A
Klinik für Kardiologie, Allgemeines Krankenhaus Celle.
Terres
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W
D002986:Clinical Trials as Topic; D003328:Coronary Thrombosis / Q000097:blood / Q000188:drug therapy*; D005343:Fibrinolytic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D006493:Heparin / Q000009:adverse effects / Q000627:therapeutic use*; D006495:Heparin, Low-Molecular-Weight / Q000009:adverse effects / Q000627:therapeutic use*; D024764:Hirudin Therapy; D006629:Hirudins / Q000009:adverse effects; D006801:Humans; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors*; D016896:Treatment Outcome
D005343:Fibrinolytic Agents; D006495:Heparin, Low-Molecular-Weight; D006629:Hirudins; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D006493:Heparin