Thrombus aspiration during percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI) is said to reduce PCI-induced distal occlusion.1-3 In an attempt to enhance its effectiveness, thrombus aspiration is often coupled with glycoprotein IIb/IIIa (GpIIb/IIIa) inhibitors, though conflicting results on this strategy have been reported so far.4-5 Indeed, GP IIb/IIIa antagonists inhibits the final common pathway that leads to platelet aggregation and leucocyte plugging which are the main components of fresh thrombi,6 but are unable to modify the morphologic characteristics of older thrombi (i.e., lytic changes and organization), which are found in nearly ¿50% of STEMI patients.7,8 Fibrinolytic agents, conversely, can weaken the structure of older thrombi and therefore have the potential to facilitate manual aspiration.9 Accordingly, we designed the DISSOLUTION (Delivery of thrombolytIcs before thrombectomy in patientS with ST-elevatiOn myocardiaL infarction Undergoing primary percuTaneous coronary interventION) trial, a prospective, randomized, single-blind trial in order to evaluate the hypothesis that intrathrombus delivery of thrombolysis prior to manual thrombectomy can enhance the efficacy of thrombus aspiration in primary PCI.
The results of this study will show whether intrathrombus delivery of thrombolysis can be an alternative strategy in order to achieve an effective thrombus aspiration during primary PCI. The pathophysiologic background of this strategy lies on the histologic demonstration that thrombotic material at the site of a coronary artery occlusion is often characterized by lytic and organized areas rather than only by layered patterns of fibrin and intact platelets, erythrocytes, and granulocytes. These observations make questionable the utility of GP IIb/IIIa antagonists, whose primary mechanism of action is inhibition of the final common pathway that leads to platelet aggregation and leucocyte plugging. Conversely, one should consider that the increase in microvascular resistance typically associated with primary PCI is caused by autochthonous fibrin, vessel wall components, circulating blood cells, and fibrinogen, which might respond to a fibrinolytic agent but not to GP IIb/IIIa inhibitors. Accordingly, a recent study has shown that low-dose intracoronary streptokinase administration immediately after primary PCI significantly improves myocardial perfusion. Also, anectodical cases of successful aspiration of large thrombi after adjunctive pulse infusion of thrombolysis after initial failed thrombectomy have been reported.
The results of our study will extend previous experiences and clarify whether the intrathrombus delivery of thrombolytic agents has the advantage of treating intraluminal clot of a thrombus-containing stenosis. Pioneering studies demonstrated in the `90s the efficacy of urokinase therapy administered by local drug-delivery catheters with conventional urokinase-infusion techniques in dissolving intraluminal clot and intramurally depositing drug at the site of arterial injury. Local delivery of urokinase by catheter-based techniques resulted in more complete lysis of intraluminal thrombus as compared with conventional urokinase infusion techniques. Mechanical deformation of thrombus, possibly due to an increase in the surface area available for thrombolysis and the physical disruption of clot, may be an important component of the mechanism of site-specific thrombolysis. Local delivery techniques also deposit significant amounts of urokinase at balloon angioplasty sites, creating an intramural reservoir of drug that may result in prolonged local thrombolysis. These earlier results indicate that the possibility exists that the higher concentration of the thrombolytic agent at the thrombus site may weaken the structure of thrombotic material making the mechanical removal of thrombus more effective and therefore reducing distal embolization.