Increased thrombin activity correlates with increased ischemic event rate after percutaneous transluminal coronary angioplasty: Lack of efficacy of locally delivered urokinase

BACKGROUND: Angiographic thrombus is associated with increased coronary occlusion and restenosis rates after angioplasty. Administration of intracoronary urokinase decreases the incidence of thrombus but is associated with an increased periprocedural event rate, including stroke and myocardial infarction. An alternative approach is to deliver the agent directly into the arterial wall, thereby reducing the thrombotic substrate in the absence of a systemic effect of the delivered agent. OBJECTIVE: This randomized, double-blind, prospective study correlated intracardiac fibrinopeptide A levels with the ischemic events after angioplasty and evaluated whether locally administered urokinase could reduce the event rate. METHODS: Fifty-four patients with acute coronary syndromes were randomly assigned to local delivery of urokinase or saline. Levels of fibrinopeptide A, a marker of thrombin activity, were obtained before and after administration of heparin, after 2 balloon inflations, and at the end of the procedure in 43 patients and were correlated with ischemic events within the 6-month follow-up period (death, myocardial infarction, or recurrent ischemia). RESULTS: Multivariant analysis revealed that an elevated fibrinopeptide A level before angioplasty significantly correlated with an increased likelihood of an adverse event over the 6-month clinical follow-up. A postangioplasty reduction in the fibrinopeptide A level was noted in control patients (P <.001), but not after local urokinase administration, and the final fibrinopeptide A level was higher in the urokinase group (P =.02). Urokinase had no effect on the procedural results. On follow-up more patients receiving urokinase (13 of 27) had ischemic events than did control patients (6 of 25, P =.04). Most events were recurrent ischemia caused by restenosis. CONCLUSIONS: Heparin-resistant thrombin activity, as evidenced by an increased fibrinopeptide A level correlates with ischemic events on long-term follow-up. Local delivery of urokinase increased the event rate.