The role of thrombin inhibition during percutaneous coronary intervention.
Acute coronary syndromes encompass a spectrum of conditions, including myocardial infarction and unstable angina. These syndromes are related to the formation and disruption of atherosclerotic plaque. Rupture of plaque leads to thrombin generation, fibrin deposition, and platelet aggregation, ultimately resulting in restriction of blood flow and ischemia of cardiac tissue. Percutaneous coronary intervention (PCI), including angioplasty and coronary stent placement, has been developed to open occluded arteries. The frequency with which these procedures are performed speaks to their largely successful outcomes. However, the mechanical manipulations of PCI result in additional plaque rupture and damage to the vessel wall, exposing subendothelial components to blood and resulting in the initiation of the clotting cascade and in platelet activation. Left unchecked, these intertwined processes lead to formation of arterial thrombi at the site of endothelial damage, and potentially to abrupt vessel closure or embolization of thrombi into the distal microcirculation. Thrombin plays a central role in thrombus formation and platelet activation, and its inhibition significantly reduces thrombus-related sequelae. Current antithrombotic strategies during PCI are based on the traditional indirect thrombin inhibitor heparin. Heparin has several limitations in efficacy and safety, due in part to its indirect mechanism of action. Bivalirudin, a direct thrombin inhibitor, offers significant improvement over heparin in the clinical outcomes and risks associated with PCI.
Wittkowsky
Ann K
AK
Department of Pharmacy, University of Washington Medical Center, Seattle 98195, USA. akwitt@u.washington.edu
D015906:Angioplasty, Balloon, Coronary / Q000009:adverse effects*; D001120:Arginine / Q000031:analogs & derivatives; D002986:Clinical Trials as Topic; D003327:Coronary Disease / Q000628:therapy*; D003328:Coronary Thrombosis / Q000209:etiology / Q000517:prevention & control; D005343:Fibrinolytic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000077425:Fondaparinux; D006493:Heparin / Q000494:pharmacology / Q000627:therapeutic use; D006629:Hirudins / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D010446:Peptide Fragments / Q000494:pharmacology / Q000627:therapeutic use; D010875:Pipecolic Acids / Q000494:pharmacology / Q000627:therapeutic use; D011134:Polysaccharides / Q000494:pharmacology / Q000627:therapeutic use; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use; D013449:Sulfonamides; D013917:Thrombin / Q000037:antagonists & inhibitors*
D005343:Fibrinolytic Agents; D006629:Hirudins; D010446:Peptide Fragments; D010875:Pipecolic Acids; D011134:Polysaccharides; D011994:Recombinant Proteins; D013449:Sulfonamides; D006493:Heparin; D001120:Arginine; D013917:Thrombin; C031942:argatroban; D000077425:Fondaparinux; C074619:bivalirudin; C083544:lepirudin