Collaborative Angiographic Patency Trial Of Recombinant Staphylokinase (CAPTORS II).

AIMS: A fibrinolytic agent more effective than streptokinase available for bolus injection with reasonable cost-effectiveness is a desirable goal. Pilot studies with bolus pegulated staphylokinase (PEG-Sak) have revealed excellent Thrombolysis In Myocardial Infarction (TIMI) 3 60-minute flow. METHODS AND RESULTS: We evaluated patients with acute ST-elevation myocardial infarction within 6 hours of chest pain onset to determine a dose of PEG-Sak that had at least equal efficacy to recombinant tissue plasminogen activator (rt-PA) while maintaining an acceptable safety profile. After the initial study of 38 patients, of whom 27 received PEG-Sak, enrollment was temporarily halted because 3 patients receiving PEG-Sak had intracranial hemorrhage: 1 at a dose of 0.15 mg/kg and 2 at a dose of 0.05 mg/kg. Overall, 378 patients were studied across a PEG-Sak dose range from 0.01 mg/kg to 0.015 mg/kg, and 122 patients received accelerated rt-PA. At the lowest dose of PEG-Sak studied, 0.01 mg/kg, there was suggestive evidence of attenuation of efficacy; the point estimate for TIMI 3 flow was 24% (95% CI 9%-38%). At doses of 0.01875 to 0.0375 mg/kg (n = 314), TIMI 3 flow rates were 33% (95% CI 27%-38%), whereas the TIMI 3 flow was 41% (95% CI 20%-61%) at the highest PEG-Sak dose studied, 0.05 mg/kg (n = 23), which was similar to that found with rt-PA, 41% (95% CI 32%-50%). CONCLUSION: The efficacy of PEG-Sak, coupled with its ease of administration, provide further impetus for further study in acute myocardial infarction.

Randomized comparison of a novel anticoagulant, vasoflux, and heparin as adjunctive therapy to streptokinase for acute myocardial infarction: results of the VITAL study (Vasoflux International Trial for Acute Myocardial Infarction Lysis).

BACKGROUND: Vasoflux is a low-molecular-weight heparin derivative that inhibits factor IXa activation of factor X and catalyzes fibrin-bound thrombin inactivation by heparin cofactor II. We studied whether vasoflux improves the results of thrombolysis with streptokinase for acute myocardial infarction. METHODS AND RESULTS: We randomized 277 patients with acute myocardial infarction to standard intravenous unfractionated heparin (UFH) or intravenous vasoflux 1, 4, 8, or 16 mg/kg as a bolus followed by 1, 4, 8, or 16 mg/kg per hour infusion, on top of streptokinase and aspirin, until angiography at 90 minutes. Patency and corrected Thrombolysis in Myocardial Infarction (TIMI) frame count were studied at 60 and 90 minutes. Rates of TIMI grade 3 flow with vasoflux at any dose (35% to 42%) were not different from UFH (41%) at either time point, nor was the corrected TIMI frame count. However, there was an excess of bleeding in the patients randomized to vasoflux 8 or 16 mg/kg: 78% and 71%, compared with 53% for UFH (P =.004 and.043, respectively). Major bleeding was observed in 13% and 28% at these vasoflux doses compared with 8% with UFH (P =.558 and.01, respectively). CONCLUSION: At doses that increase the risk of bleeding, the addition of vasoflux to streptokinase and aspirin did not lead to improved patency rates compared with UFH. Targeting factor IXa and heparin cofactor II may not be a useful adjunct to thrombolysis.

Safety and efficacy of eptifibatide vs placebo in patients receiving thrombolytic therapy with streptokinase for acute myocardial infarction; a phase II dose escalation, randomized, double-blind study.

AIMS: Thrombolytic therapy restores coronary patency in patients with acute myocardial infarction, although normal perfusion (TIMI 3 flow) is not achieved in all patients. In an attempt to improve TIMI 3 flow, a combination of full-dose streptokinase, aspirin and escalating dosages of a platelet glycoprotein IIb/IIIa receptor blocker, eptifibatide, vs placebo were tested. METHODS AND RESULTS: A bolus of 180 microg. kg(-1)of eptifibatide was administered in each group, followed by a 72 h continuous infusion of 0.75 (44 patients), 1.33 (n=45) and 2.00 microg. kg(-1). min(-1)(n = 30); 62 patients received placebo. Normal perfusion (TIMI 3 flow) at 90 min was observed in 31% of placebo patients compared to 46, 42 and 45% in the ascending eptifibatide groups (44% for combined eptifibatide groups, P = 0.07). Patency (TIMI 2 and 3 flow combined) increased from 61% (placebo) to 78% for the combined eptifibatide groups (P = 0.02). Reocclusion was infrequent. No differences were observed in TIMI flow grades among eptifibatide groups. Major and minor bleeding was increased and occurred mainly at the arterial puncture site. CONCLUSION: A combination of full dose streptokinase with different eptifibatide regimens enhanced coronary perfusion, but bleeding risk was excessive. Additional trials are needed with different dosage regimens to determine the optimal combination of fibrinolytic agents and platelet glycoprotein IIb/IIIa receptor blockers.