Objectives. Our aim was to design and evaluate a new and easily administered recombinant tissue-type plasminogen activator (rt-PA) regimen for thrombolysis in acute myocardial infarction (AMI) based on established pharmacokinetic data that improve the reperfusion success rate.
Background. Rapid restoration of Thrombolysis in Myocardial Infarction (TIMI) grade 3 flow is a primary predictor of mortality after thrombolysis in AMI. However, TIMI grade 3 patency rates 90 min into thrombolysis of only 50% to 60% indicate an obvious need for improved thrombolytic regimens.
Methods. Pharmacokinetic simulations were performed to design a new rt-PA regimen. We aimed for a plateau tissue-type plasminogen activator (t-PA) plasma level similar to that of the first plateau of the Neuhaus regimen. These aims were achieved with a 20-mg rt-PA intravenous (i.v.) bolus followed by an 80-mg i.v. infusion over 60 min (regimen A). This regimen was tested in a consecutive comparative trial in 80 patients versus 2.25 106 IU of streptokinase/60 min (B), and 70 mg (C) or 100 mg (D) of rt-PA over 90 min. Subsequently, a confirmation trial of regimen A in 254 consecutive patients was performed with angiographic assessment by independent investigators of patency at 90 min.
Results. The comparative phase of the trial yielded, respectively, TIMI grade 3 and total patency (TIMI grades 2 and 3) of 80% and 85% (regimen A), 35% and 50% (B), 50% and 55% (C) and 60% and 70% (D). In the confirmation phase of the trial, regimen A yielded 81.1% TIMI grade 3 and 87.0% total patency. At follow-up angiography 7 (4.1%) of 169 vessels had reoccluded. In-hospital mortality rate was 1.2%. Nadir levels of fibrinogen, plasminogen and alpha2-antiplasmin were 3.6 ± 0.8 mg/ml, 60 ± 21% and 42 ± 16%, respectively (mean ± SD). Fifty-seven patients (22.4%) suffered from bleeding; 3.5% needed blood transfusions.
Conclusions. The 60-min alteplase thrombolysis in AMI protocol achieved a TIMI grade 3 patency rate of 81.1% at 90 min with no indication of an increased bleeding hazard; it was associated with a 1.2% overall mortality rate. These results are substantially better than those reported from all currently utilized regimens. Head to head comparison with established thrombolytic regimens in a large-scale randomized trial is warranted. 相似文献
Inability to access occluded grafts is a major limitation to successful thrombolysis and may even preclude it. This paper addresses the problem and offers a new technique of direct puncture of prosthetic grafts through which thrombolysis and angioplasty can be performed. These techniques resulted in accelerated thrombolysis in all 15 patients studied with no failures due to inability to attain graft access. 相似文献
Quantitative angiography was performed in 68 out of 123 patientstreated with intravenous rt-PA for acute myocardial infarction.At 90 min angiography, the median minimal cross-sectional areawas 1.11 mm2 and the median percentage area stenosis was 80%.A percentage area stenosis greater than 70% was seen in 78%of the patients. Patients with a patent infarct related artery at the first angiogramwere randomized to receive subsequent infusions either of rt-PA+ heparin or placebo + heparin. There was a persistent trendof improvement in minimal lumen diameter and percentage diameterstenosis of the residual stenosis in the infarct related arteryin both treatment groups when re-examined 624 hours laterand at the time of hospital discharge. A reduction in plaquearea, the area between the detected and the referencecontours of the infarct related segment, was more frequentlyseen in patients receiving a second infusion of rt-PA than inpatients with no prolonged thrombolytic therapy (83% versus57%, P<0.025, chi square). 相似文献