Acute coronary syndromes: Pathophysiology and therapeutic aspects

This article discusses recent developments in the field of acute coronary s yndromes including pathophysiological mechanisms as well as therapeutic str ategies. A plaque disruption is caused by different stimuli in a plaque pro ne to rupture, i.e. a plaque with a lipid-rich core and high local concentr ation of inflammatory cells (T-cells, monocytes/macrophages, mast cells). T hese cells are capable of producing matrix degradation products and can red uce stability of a plaque. Thrombus formation, based on platelet activation and aggregation as well as fibrin formation, is the main consequence of pl aque disruption. Depending on the degree of thrombus formation occlusion is followed clinically by unstable angina (subtotal occlusion) or by acute my ocardial infarction (total occlusion). Accompanying vasoconstriction may fu rther aggravate the situation. Principles of therapy are thrombus dissoluti on as well as prevention of new thrombus formation: main goals of thromboly tic therapy in acute myocardial infarction are a prompt (less than 3 hours) , complete, and sustained (prevention of early thrombotic reocclusion) repe rfusion. Within the last years the "gold" standard of thrombolytic therapy has been the "front loaded" rt-PA (alteplase) regimen (bolus + 90 min. infusion). Bi ochemically engineered mutants of t-PA e.g. r-PA (reteplase); n-PA (lanotep lase) and TNK-PA can be infused as double or single bolus and have been sho wn in recent studies to be at least as effective as rtPA (GUSTO-1, InTIME-2 , ASTENT-2). New therapeutic options in unstable angina and non-Q-wave MI a re low-molecular weight heparins (antithrombins) and glycoprotein IIb/IIIa- blockers (platelet inhibitors). It is at the moment point of discussion and goal of ongoing trials whether one of the differ ent agents within these n ew classes of antithrombotic drugs is superior to another in certain indica tions.