title: Overcoming thrombolytic resistance: rationale and initial clinical experience combining thrombolytic therapy and glycoprotein IIb/IIIa receptor inhibition for acute myocardial infarction.
abstract: OBJECTIVE
  We sought to review the emerging data and the clinical rationale for combining glycoprotein (GP) IIb/IIIa inhibitors with thrombolytic therapy for acute myocardial infarction (AMI).
  
  
  BACKGROUND
  Although thrombolytic therapy has been a major advance in the treatment of acute ST segment elevation MI, new single-bolus thrombolytic agents have been unable to break the "thrombolytic ceiling" in infarct-related artery (IRA) patency.
  
  
  METHODS
  Recent literature on GPIIb/IIIa inhibitors in acute coronary syndromes was reviewed.
  
  
  RESULTS
  A new approach toward improving current thrombolytic-antithrombotic regimens focuses on "targeted therapy" for each component of the occlusive coronary thrombus: fibrin, thrombin and platelets. For the fibrin component, front-loading and/or bolus dosing of plasminogen activators (PAs) has identified the currently available doses of tissue-type plasminogen activator (t-PA) and recombinant tissue-type plasminogen activator (r-PA). For the thrombin component, several recent trials have shown that lower doses of heparin improve the safety profile of the thrombolytic-antithrombotic regimen. For the platelet component, aspirin has been shown to be effective, but the GPIIb/IIIa inhibitors offer the potential for more effective platelet inhibition and improved clinical efficacy. The benefits of GPIIb/IIIa inhibition in reducing death, MI or urgent revascularization in the setting of percutaneous coronary intervention are well established. Emerging experimental and clinical data now suggest that combining GPIIb/IIIa inhibition with reduced-dose thrombolytic therapy may improve early IRA patency without increasing bleeding risk.
  
  
  CONCLUSIONS
  Given the strong clinical and physiologic rationale, clinical investigation in acute ST segment elevation MI is currently focused on combining the potent GPIIb/IIIa receptor inhibitors with reduced-dose fibrinolytic agents in acute MI, with the goal of overcoming "thrombolytic resistance."
authors.affiliation: Cardiovascular Division, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA. ccannon@rics.bwh.harvard.edu
authors.forename: C P
authors.initials: CP
authors.lastname: Cannon
mesh_terms: D000077284:Abciximab; D015906:Angioplasty, Balloon, Coronary; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000627:therapeutic use; D009203:Myocardial Infarction / Q000188:drug therapy*; D015539:Platelet Activation; D010973:Platelet Adhesiveness; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors*; D015607:Stents; D015912:Thrombolytic Therapy; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D007140:Immunoglobulin Fab Fragments; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D000077284:Abciximab