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

OBJECTIVES We sought to review the emerging dat and the clinical rationale for combining glycoprotein (GP) IIb/III inhibitors with thrombolytic therapy for acute myocardial infarction (AMI). BACKGROUND Although thrombolytic therapy has been 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/III inhibitors in acute coronary syndromes was reviewed. RESULTS 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/III inhibitors offer the potential for more effective platelet inhibition and improved clinical efficacy. The benefits of GPIIb/III inhibition in reducing death, MI or urgent revascularization in the setting of percutaneous coronary intervention are well established. Emerging experimental and clinical dat now suggest that combining GPIIb/III inhibition with reduced-dose thrombolytic therapy may improve early IR 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/III receptor inhibitors with reduced-dose fibrinolytic agents in acute MI, with the goal of overcoming “thrombolytic resistance.”