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.