Combined intravenous thrombolysis

Keris V, Rudnicka S, Vorona V, Enina G, Tilgale B, Fricbergs J. Combined intraarterial/ intravenous thrombolysis for acute ischemic stroke. Am JNeuroradiol 2001 22 352-358. 

Comparisons between the different intra-arterial thrombolysis trials and between intraarterial thrombolysis and intravenous thrombolysis is hampered by differences in methodology and type of thrombolytic therapy. In addition, within the intra-arterial thrombolysis trials, thrombolytic deUvery has varied between regional into a parent vessel of the thrombosed vessel, local into the affected artery and into the thrombus itself, or combinations of these methods. In addition, the infusion process has been variable, ranging from continuous to pulsed infusion. Some studies have allowed physical clot dispersion using the tip of the microcatheter while this was prohibited in others, for instance in the PROACT trials. 

The GUSTO trial demonstrated that treatment of patients within 6 hours after onset of symptoms with the combination of a clot-selective thrombolytic agent [recombinant tissue type plasminogen activator (t-PA)] plus conjunctive treatment with aspirin and intravenous unfractionated heparin resulted in 30-day mortality of 6.3% (6). An angiographic substudy demonstrated that patency of the infarct-related artery was not the sole determinant of outcome. Restoration of normal coronary flow after thrombolysis was found to be critical in lowering mortality (7). Thus, angiographic analysis demonstrated that both induction of culprit artery patency and the extent of restoration of flow were determinants of outcome. 

Three influential studies explore thrombolysis followed by obligatory coronary intervention compared with thrombolysis alone. These results diminished enthusiasm for a combined approach. A primary objective of one component of the TIMI II trial (TTMI Ha) was to determine whether early invasive management after acute STEMI would improve outcome (12). Patients eligible for enrollment in TTMI n were those with symptoms of less than 4 hours in duration and electrocardiographic manifestations of acute STEMI. All patients were treated with intravenous recombinant t-PA. In addition to t-PA, patients were treated with contemporary conjunctive and adjunctive therapy that included aspirin, unfractionated heparin, and intravenous hdocaine for a minimum of 24 hours. Within 1 hour after onset of infusion of t-PA, patients were given a bolus of 5000 units of unfractionated heparin in addition to a continuous infusion of 10(X) units per dose to induce a 1.5- to 2-fold... 

---