Overcoming thrombolytic resistance - Rationale and initial clinical experience combining thrombolytic therapy and glycoprotein IIb/IIIa receptor inhibition for acute myocardial infarction

OBJECTIVES: 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 tic 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." (C) 1999 by the American College of Cardiology.