An overview of the patency and stroke rates following thrombolysis with streptokinase, alteplase, and anistreplase used to treat an acute myocardial infarction

The results of an overview of early (90-240 min) and late (24 hours or more) patency and of stroke rates for each of the three commercially available thrombolytic agents, streptokinase, alteplase, and anistreplase are presented. Studies included in this analysis are all those published between 1985 and March 1992 and focus on the licensed dosage regimens of each agent. The rates of early and late patency for streptokinase were 64.7% and 80.8%; for alteplase, 66.6% and 73.7%; and for anistreplase, 72.1% and 84.5%. The rates of total and hemorrhagic stroke for streptokinase were 0.69% and 0.17%; for alteplase, 1.27% and 0.50%; and for anistreplase 0.91% and 0.38%. These results provided evidence that the rates of early and late patency appeared to be greatest for anistreplase and that the rates of stroke are within "acceptable" ranges for all three thrombolytic agents with streptokinase affording the lowest rate.     

Are the various thrombolytic agents equally effective in the treatment of acute transmural myocardial infarction?

While it is no longer possible to imagine the treatment of an acute transmural myocardial infarction without the use of thrombolytic agents, some discussion still exists as to the choice of the thrombolytic agent. Our study concerns a group of 160 patients with an acute transmural myocardial infarction, 60 of whom were treated with anistreplase, 52 with streptokinase and 48 with alteplase. Statistically, the administration of anistreplase was associated with a significantly higher frequency of ventricular arrhythmias in comparison to the other thrombolytic agents, whereas after subsequent coronary angiography, the anistreplase group revealed a significantly lower number of completely occluded coronary arteries. The data from this study demonstrate that anistreplase is a very valuable thrombolytic agent. It may even be more effective than streptokinase and alteplase in the treatment of acute myocardial infarction when the patency of the coronary arteries 1 month after the acute coronary event is considered the primary endpoint.     

Intracoronary infusion of streptokinase in patients with acute myocardial infarction: Effects of reperfusion on left ventricular performance

Cardiac catheterization and coronary angiography were performed on hospital admission in 32 consecutive patients with acute myocardial infarction. Twenty-six patients had total occlusion of an infarct-related coronary artery and six had severe proximal stenosis with poor distal flow. In 18 of the 26 patients with total occlusion, intracoronary infusion of Streptokinase resulted in reperfusion of the distal coronary artery. Seventeen of these 18 patients had severe coronary arterial stenosis at the site of the previous total occlusion. Hemodynamic indexes of left ventricular performance and ejection fraction determined by gated cardiac blood pool imaging did not change immediately after reperfusion (p [probability]= not significant [NS]). The mean (± standard deviation) left ventricular ejection fraction increased significantly (p = 0.007) from admission (44 ± 15 percent) to hospital discharge (55 ± 7 percent) in patients evidencing reperfusion of the occluded coronary artery. It did not change (p = NS) in this time span in the patients with severe stenosis alone, in those with total occlusion not demonstrating reperfusion after administration of streptokinase or in an additional 10 control patients with acute myocardial infarction not evaluated with coronary angiography. These data suggest that (1) coronary arterial thrombus is frequent in acute myocardial infarction and can be lysed by intracoronary streptokinase; (2) reperfusion with intracoronary streptokinase in acute myocardial infarction results in improved left ventricular performance between admission and hospital discharge.     

Angiographically assessed coronary arterial patency and reocclusion in patients with acute myocardial infarction treated with anistreplase: results of the anistreplase reocclusion multicenter study (ARMS).

In this open multicenter study, 156 patients with acute myocardial infarction received 30 U of anistreplase intravenously over 5 minutes within 4 hours of the onset of chest pain. The patency of the infarct-related vessel was determined by coronary angiography 90 minutes after anistreplase treatment, and also 24 hours after treatment, in patients with a patent infarct-related vessel at 90 minutes, to assess the reocclusion rate. The investigators categorized the infarct-related vessel as patent or occluded, and 2 independent cardiologists graded the infarct-related vessel according to the Thrombolysis in Myocardial Infarction (TIMI) perfusion criteria. At the 90-minute assessment, 106 of 145 evaluable patients (73%) had patent infarct-related vessels, and 39 of 145 (27%) had occluded infarct-related vessels. Of the 139 independently assessed patients, 98 (71%) had TIMI grades 2 or 3 and 41 (29%) had TIMI grades 0 or 1. At the 24-hour assessment, 98 of 102 patients (96%) had a patent infarct-related vessel, and reocclusion had occurred in 4 of 102 patients (4%). Of the 94 independently assessed patients 90 (96%) had TIMI grades 2 or 3, and 4 (4%) had TIMI grades 0 or 1. The reliability of noninvasive parameters as indicators of achieved patency of the infarct-related vessel was estimated by means of correlation with patency assessed by coronary angiography. A significant correlation of 0.62 was found. The patency rate of 71 to 73% after use of anistreplase in patients with acute myocardial infarction corresponds with findings in earlier studies. The low reocclusion rate of 4% after use of anistreplase probably reflects the prolonged action of anistreplase.     

Comparative safety of thrombolytic agents.

Three available thrombolytic agents, streptokinase, alteplase, and anistreplase, have been shown to have similar effects on preservation of left ventricular function and mortality reduction after acute myocardial infarction (AMI). The agents are, however, quite different with respect to their safety profiles. Clinical trials to date suggest that alteplase (tissue plasminogen activator) or anistreplase administration is associated with a high incidence of cerebral hemorrhage. In contrast, streptokinase is associated with a low rate of cerebral hemorrhage. Streptokinase and anistreplase are associated with a higher risk of allergic reaction when compared with alteplase. Hypotension is also more common with streptokinase and anistreplase, but occurs significantly with alteplase as well. Alteplase is associated with a lower reinfarction rate when compared with streptokinase and anistreplase. The Third International Study of Infarct Survival (ISIS-3), a direct comparison of 3 thrombolytic agents (streptokinase, anistreplase, and duteplase), may provide some insight regarding the safety of these agents. Because these agents have been shown to be equally effective, selection of an appropriate agent for an individual patient may depend more on assessment of the likelihood of an adverse event or other factors, such as cost or convenience of administration, rather than assessment of the probability of greater benefit with a particular agent.     

Invasive reperfusion study II. Multicentre European randomized trial of anistreplase vs streptokinase in acute myocardial infarction

IRS II (Invasive reperfusion study II) was a multicentre randomizedtrial comparing the efficacy of a 2–5-min 30 U anistreplaseintravenous injection with a 1 500 000 U 60-min streptokinase(SK) intravenous infusion in acute myocardial infarction. 116patients were randomized within 6 h of onset of symptoms. Earlycoronary patency was assessable in 107 patients by coronaryangiogram performed 102 min after thrombolytic treatment (range:30–297 min) in the anistreplase group and 93 min (range:22–330 min) in the SK group. The early coronary patencyrate was significantly higher in the anistreplase group thanin the SK group: respectively, 70% (38/54) and 51% (27/53),P<0.05. Fifty patients had assessable coronary angiogramsat 90 min and 24 h. The 24-h patency rate was 92.3% (24/26)in the anistreplase group vs 87.5% (21/24) in the SK group.No early reocclusion occurred in the anistreplase group vs 15.4%(2/13) in the SK group (NS). Fibrinogen fell to 13.2 ±19.8%on anistreplase vs 9.4 ±10.3% on SK (NS). Bleeding complicationsoccurred in 12% (7/58) of treated patients in the anistreplasegroup vs 20.7% (13/58) in the SK group (NS). Two cerebrovascularaccidents occurred after thrombolytic treatment with anistreplase(3.4%) vs one after SK (1.7%) (NS). Thus, anistreplase is moreeffective than intravenous SK and easier to administer.     

Pre-hospital thrombolytic therapy with either alteplase or streptokinase: Practical applications, complications and long-term results in 529 patients

OBJECTIVE: To assess the practical application, safety and long-term outcomeof pre-hospital thrombolytic intervention with either alteplaseor streptokinase in patients with extensive myocardial infarction. DESIGN: Prospective study. SUBJECTS: Patients with chest pain of more than 30 min duration, presentingwithin 6 h of symptom onset and with electrocardiographic evidenceof extensive evolving myocardial infarction. METHODS: Eligibility of patients was established by the general practitioneror the ambulance nurse using a standardized questionnaire with(contra-) indications for thrombolytic therapy. ComputerizedECG was recorded by ambulance nurses. In the presence of extensiveST segment elevation (sum ST deviation of at least 1·0m V), eligible patients received either 100 mg alteplase (n=246)or 50 mg alteplase in the ambulance followed by 0·75x 10⁶ IE streptokinase in hospital (n=90), or 1·5 x 10⁶IE streptokinase intravenously (n=193). MAIN OUTCOME MEASUREMENTS: Death and life-threatening complications (ventricular fibrillation,cardiac arrest) and side effects (hypotension, allergic reactions)during transportation to hospital and in the first 24 h followinghospitalization, and survival up to 5 years follow-up. RESULTS: From 1988–1993, 529 patients received thrombolytic treatmentinitiated pre-hospital. The time gained by pre-hospital administrationof thrombolysis amounted to 50 min. The rate of complicationsduring transportation and during the first 24 h after hospitalizationwas low. Hospital mortality was 2% and 1-year mortality 3%.Cumulative survival at 5 years was 92%. This was superior tothe 84% 5-year survival observed in a matched group of 239 patientswith similar baseline characteristics treated with alteplasein hospital. CONCLUSIONS: Pre-hospital administration of either alteplase or streptokinaseis feasible and safe and results in significant time gain. Thelong-term prognosis is excellent in spite of extensive evolvingmyocardial infarction upon admission.     

Use of left ventricular function as an end point of thrombolytic therapy.

In recent acute myocardial infarction, early reperfusion of the infarct-related artery by intracoronary or intravenous thrombolytic therapy induces a significant limitation of infarct size, provided reperfusion occurs within a time frame that myocardial salvage can still be expected. Limitation of infarct size reduces scar tissue formation, aneurysm formation, infarct zone expansion, left ventricular volume enlargement, and eventually results in higher left ventricular ejection fraction. Infarct size limitation and left ventricular function preservation occur with all thrombolytic agents currently in clinical use: streptokinase, alteplase and, more recently, anistreplase. When anistreplase is compared with conventional heparin therapy, a 31% reduction in infarct size is found (estimated from single photon emission computed tomography, or SPECT). This translates into a significant preservation of left ventricular ejection fraction as observed in anistreplase-treated patients compared with heparin-treated patients (0.53 +/- 0.13 vs 0.47 +/- 0.12, p less than 0.002). In comparative trials of 2 thrombolytic agents, anistreplase was demonstrated to be as efficient as alteplase on left ventricular ejection fraction preservation and infarct size limitation.     

Coronary artery reperfusion in acute myocardial infarction: Beneficial effects of intracoronary streptokinase on left ventricular salvage and performance

Coronary angiography was performed on hospital admission in 37 patients with acute myocardial infarction (AMI). Thirty patients had total occlusion of the infarct-related coronary artery and seven patients had severe proximal stenoses with poor distal flow. In 20 of 30 patients with total occlusion, intracoronary (IC) infusion of streptokinase (SK) resulted in reperfusion of the distal coronary artery. Left ventricular (LV) performance was assessed before coronary angiography and at discharge from the hospital by use of gated cardiac blood pool imaging techniques. In patients evidencing reperfusion of the infarct-related coronary artery, mean (± SD) left ventricular ejection fraction (LVEF) increased from admission through discharge (46% ± 15% to 55% ± 10%, p = 0.002). In contrast, LVEF did not change from admission through discharge in patients with severe proximal stenoses alone or in patients with total occlusion who did not demonstrate reperfusion following SK administration (47% ± 17% vs 49% ± 18%, p = ns). In an additional 14 control patients with AMI who were not evaluated with coronary angiography, LVEF did not change from admission through discharge (46% ± 12% vs 48% ± 14%, p = ns). Quantitative thallium-201 perfusion imaging demonstrated an increase (p < 0.05) in thallium uptake in the infarct segment following coronary artery reperfusion. In contrast, thallium uptake did not change (p = ns) in the infarct segment in patients not evidencing angiographic coronary artery reperfusion. These data support the following: (1) Coronary artery thrombus occurs frequently in AMI and can be lysed by IC SK, and (2) reperfusion with IC SK in patients with evolving myocardial infarction results in myocardial salvage and improved LV performance through hospital discharge.     

Angiographic findings and catheterization laboratory events in patients with primary coronary angioplasty or streptokinase therapy for acute myocardial infarction

Background: The purpose of this study was to evaluate catheterizationlaboratory events and angiographic findings in patients randomlyassigned to undergo primary coronary angioplasty or to receiveintravenous streptokinase for acute myocardial infarction. Methods: We analysed angiographic data in 301 patients withacute myocardial infarction, randomly assigned to undergo primarycoronary angioplasty without antecedent thrombolytic therapyor to receive intravenous streptokinase therapy. Follow-up coronaryangiography was preferably performed after 3 months. AII angiogramswere analysed with a quantitative coronary analysis system. Results: Of the 152 patients assigned to angioplasty treatment,140 underwent this procedure with a success rate of 97%. Theresidual diameter stenosis of the infarct-related vessel immediatelyafter angioplasty was 27 ± 15% and there were major eventsin 14% of the patients in the catheterization laboratory. Atfollow-up angiography after a mean interval of 92 days in theangioplasty assigned patients, a diameter stenosis of 35 ±22% was observed in this group. The restenosis rate was 28%and the reocclusion rate 5%. A Thrombolysis in Myocardial Infarction(TIMI) grade 2 flow immediately after angioplasty was predictivefor reocclusion at follow-up (P= 0.001). In the streptokinaseassigned patients (149) the infarct-related vessel was patentat follow-up angiography after a mean of 22 days in 66% of thepatients with a mean residual diameter stenosis of 77 ±20%. Conclusion: Primary coronary angioplasty is a highly effectiveand safe reperfusion modality for patients with acute myocardialinfarction. However, TIMI grade 2 flow through the infarct-relatedvessel immediately after angioplasty is a predictor of reocclusion.     

Pre-dosing antibody levels and efficacy of thrombolytic drugs containing streptokinase.

OBJECTIVE--To evaluate the influence of pretreatment streptokinase resistance titre and the concentration of IgG antibodies to streptokinase on the efficacy of thrombolytic drugs containing streptokinase in restoring coronary patency in acute myocardial infarction. DESIGN--Comparative observational study. SETTING--City general hospital. PATIENTS--One hundred and twenty four previously unexposed patients presenting within six hours of onset of acute myocardial infarction. INTERVENTIONS--Streptokinase, 1.5 MIU as intravenous infusion over 60 minutes (60 patients), or anistreplase, 30 units as intravenous injection over five minutes (64 patients). MAIN OUTCOME MEASURES--Pretreatment streptokinase resistance titre and concentration of IgG antibodies to streptokinase were measured in 96 and 124 patients respectively and coronary patency assessed angiographically at 90 minutes and 24 hours. RESULTS--Pretreatment streptokinase resistance titre and concentrations of IgG antibodies to streptokinase were low and skewed towards higher values. Those patients with coronary occlusion at 24 hours had a significantly higher median streptokinase resistance titre (100 v 50 streptokinase IU ml-1, P = 0.02). There were trends towards a higher streptokinase resistance titre in those patients with coronary occlusion at 90 minutes (50 v 20 streptokinase IU ml-1, P = 0.06) and higher concentrations of IgG antibodies to streptokinase in those with coronary occlusion at both 90 minutes and 24 hours (1.53 v 0.925, P = 0.03; 1.65 v 1.04 micrograms streptokinase binding ml-1, P = 0.06). Coronary patency rates were similar in the two treatment groups. CONCLUSIONS--In the range measured in previously unexposed patients the streptokinase resistance titre has a small, but significant, negative influence on the efficacy of streptokinase and anistreplase. This effect should be considered if retreatment with streptokinase or anistreplase is proposed.     

Residual coronary stenosis after thrombolysis with rt-PA or streptokinase: acute results and 3 weeks follow-up

Ninety-one patients with acute myocardial infarction were assignedto intravenous treatment with streptokinase or rt-PA as partof the randomized trial carried out by the European Study Groupfor Recombinant Tissue-Type Plasminogen Activator (rt-PA). Apatent coronary artery was found in 37 of 45 (82%) patientstreated with rt-PA and in 27 of 46 (59%) patients treated withstreptokinase 75–90 minutes after start of infusion. Patientswere subsequently anticoagulated with heparin or dicoumarolup to a repeat angiography 3 weeks after the infarction.Of the64 patients with successful reperfusion, 3 died and 3 sufferedreocclusion of the vessel. Quantitative analysis of the coronarystenosis both immediately after thrombolvsis and at 3 weeksfollow-up was possible in 33 cases. Residual stenosis (percentagenarrowing of diameter) decreased from 74± 14% to 56±17% P<0.05). No difference was observed between the groupsof patients treated with streptokinase (74±9% to 57±12%,N = 17) and with rt-PA (74±17% to 56±21%, N =16). Despite the significant regression, a coronary stenosisof more than 50% of the diameter persisted in 82% of the patientsthree weeks after the infarction.     

Residual coronary stenosis after thrombolysis with rt-PA or streptokinase: acute results and 3 weeks follow-up

Ninety-one patients with acute myocardial infarction were assignedto intravenous treatment with streptokinase or rt-PA as partof the randomized trial carried out by the European Study Groupfor Recombinant Tissue-Type Plasminogen Activator (rt-PA). Apatent coronary artery was found in 37 of 45 (82%) patientstreated with rt-PA and in 27 of 46 (59%) patients treated withstreptokinase 75–90 minutes after start of infusion. Patientswere subsequently anticoagulated with heparin or dicoumarolup to a repeat angiography 3 weeks after the infarction.Of the64 patients with successful reperfusion, 3 died and 3 sufferedreocclusion of the vessel. Quantitative analysis of the coronarystenosis both immediately after thrombolvsis and at 3 weeksfollow-up was possible in 33 cases. Residual stenosis (percentagenarrowing of diameter) decreased from 74± 14% to 56±17% P<0.05). No difference was observed between the groupsof patients treated with streptokinase (74±9% to 57±12%,N = 17) and with rt-PA (74±17% to 56±21%, N =16). Despite the significant regression, a coronary stenosisof more than 50% of the diameter persisted in 82% of the patientsthree weeks after the infarction.     

Overview of patency as an end point of thrombolytic therapy.

Underlying the use of thrombolytic therapy is the hypothesis that reestablishment and maintenance of coronary blood flow (coronary patency) are the primary mechanisms of therapeutic benefit in patients with acute myocardial infarction. Early achievement and maintenance of adequate coronary blood flow (patency) in the infarct-related artery are the primary goals of thrombolytic therapy. One third of patients may achieve spontaneous patency within a few days following acute myocardial infarction. When antithrombotic therapy (i.e., heparin) is administered, this rate increases to greater than 50%, but patency is achieved only gradually and mortality reductions comparable to thrombolytic therapy are not achieved. After administration of a thrombolytic agent, early (90-minute) patency rates are greater with alteplase or anistreplase than with streptokinase. However, patency rates for alteplase decline by 10-30% if intravenous heparin is not given concurrently. When patency is assessed greater than 24 hours following thrombolytic therapy, no significant difference exists among the agents. A single angiographic observation of the artery at 90 minutes, although useful, may be inadequate to distinguish among the beneficial clinical effects of different thrombolytic regimens. The overall reperfusion or patency profile is probably a better basis for assessing relative benefits. Intravenous thrombolytic regimens that are increasingly effective in rapidly achieving and maintaining coronary patency are now available and in further development.     

ESPRIT: a European study of the prevention of reocclusion after initial thrombolysis with duteplase in acute myocardial infarction

BACKGROUND: The goal of thrombolytic treatment in acute myocardial infarctionis reperfusion of the infarct-related coronary artery. Duteplaseis a double-chain recombinant tissue-type plasminogen activator.Its efficacy and safety were evaluated in patients with acutemyocardial infarction treated within 4 h of onset of chest painin this multicentre, open, non-controlled trial. METHODS AND RESULTS: A total of 273 patients were enrolled and treated with duteplase0·6 . MU. kg^–1 over 4 h, with concomitant oralaspirin and intravenous heparin. Coronary arteriography wasperformed at 60 min, 90 min and approximately 24 h after thestart of duteplase infusion to assess the perfusion grade (TIMIscoring) of the infarct-related coronary artery. Safety wasassessed by monitoring patients closely for bleeding and forall other adverse experiences during the 72-h study period.Reinfarction during the study period was also recorded, anddeaths at any time during the period in hospital were documented. TIMI: grade 2 or 3 patency of the infarct-related coronary arteryat 90 min was achieved in 70% of the patients and 7% of these‘patent’ infarct-related coronary arteries had reoccludedby 20 to 36 h. Clinical reinfarction during the 72-h study periodwas observed in 7%. Total in-hospital mortality was 8%. Seriousor life-threatening bleeding occurred in 4% of the patients.There was one haemorrhagic stroke, and this was fatal. CONCLUSIONS: Weight-adjusted duteplase infusion, together with oral aspirinand intravenous heparin, in acute myocardial infarction resultedin patency of the infarct-related coronary artery and a safetyprofile comparable to those reported for the other form of tissue-typeplasminogen activator, alteplase, However, there remains a problemwith reocclusion and reinfarction after initially successfulthrombolysis. (Eur Heart J 1996; 17: 1522–1531)     

Coronary recanalization rate after intravenous bolus of alteplase in acute myocardial infarction.

The demonstration in animals that recombinant tissue-type plasminogen activator produces prolonged thrombolysis after its clearance from the circulation has prompted a few pilot studies of bolus administration in patients. Alteplase (bolus dose of 70 mg) resulted in the highest recanalization rate in our previous pilot study comparing bolus doses of 50, 60 and 70 mg of alteplase in patients with acute myocardial infarction. The aim of the present trial was to assess the efficacy and safety of the same bolus dose in a larger number of patients. A further objective was to study the angiographic reocclusion rate at 12 to 24 hours in patients who had a recanalized infarct-related coronary artery at 90 minutes and were randomized at that time to a bolus dose or an infusion for 3 hours of 30 mg of alteplase. Sixty patients with acute myocardial infarction and angiographically documented total occlusion of the infarct-related coronary artery before thrombolysis were treated within 5 hours of onset of symptoms with an intravenous 70-mg bolus dose of alteplase (or 80 mg if body weight was greater than or equal to 90 kg). Each patient received 5,000 IU of heparin intraarterially and 100 mg of aspirin by mouth before administration of alteplase. Coronary angiography was repeated 60 and 90 minutes after alteplase administration. The recanalization rate of the infarct-related coronary artery was 55% (95% confidence interval, 43 to 66%) at 60 minutes and 48% (95% confidence interval, 37 to 60%) at 90 minutes. Pretreatment levels of lipoprotein (a) were not significantly related to recanalization.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pre-hospital thrombolytic therapy with either alteplase or streptokinase: Practical applications, complications and long-term results in 529 patients

OBJECTIVE: To assess the practical application, safety and long-term outcomeof pre-hospital thrombolytic intervention with either alteplaseor streptokinase in patients with extensive myocardial infarction. DESIGN: Prospective study. SUBJECTS: Patients with chest pain of more than 30 min duration, presentingwithin 6 h of symptom onset and with electrocardiographic evidenceof extensive evolving myocardial infarction. METHODS: Eligibility of patients was established by the general practitioneror the ambulance nurse using a standardized questionnaire with(contra-) indications for thrombolytic therapy. ComputerizedECG was recorded by ambulance nurses. In the presence of extensiveST segment elevation (sum ST deviation of at least 1.0 m V),eligible patients received either 100 mg alteplase (n=246) or50 mg alteplase in the ambulance followed by 0.75 x 10⁶ IE streptokinasein hospital (n=90), or 1.5 x 10⁶ IE streptokinase intravenously(n=193). MAIN OUTCOME MEASUREMENTS: Death and life-threatening complications (ventricular fibrillation,cardiac arrest) and side effects (hypotension, allergic reactions)during transportation to hospital and in the first 24 h followinghospitalization, and survival up to 5 years follow-up. RESULTS: From 1988–1993, 529 patients received thrombolytic treatmentinitiated pre-hospital. The time gained by pre-hospital administrationof thrombolysis amounted to 50 min. The rate of complicationsduring transportation and during the first 24 h after hospitalizationwas low. Hospital mortality was 2% and 1-year mortality 3%.Cumulative survival at 5 years was 92%. This was superior tothe 84% 5-year survival observed in a matched group of 239 patientswith similar baseline characteristics treated with alteplasein hospital. CONCLUSIONS: Pre-hospital administration of either alteplase or streptokinaseis feasible and safe and results in significant time gain. Thelong-term prognosis is excellent in spite of extensive evolvingmyocardial infarction upon admission.     

Monitoring of streptokinase resistance titre in acute myocardial infarction patients up to 30 months after giving streptokinase or anistreplase and related studies to measure specific antistreptokinase IgG

Objective—To examine the induction of antistreptokinase antibodies after giving streptokinase or anistreplase to patients with acute myocardial infarction.Design—Patients were randomly allocated to receive either 1·5 × 10⁶ IU, streptokinase or 30U anistreplase in a double blind study. Blood samples were collected immediately before treatment and subsequently at intervals up to 30 months; plasma samples were assayed for streptokinase resistance titre (functional assay) and streptokinase binding by IgG (microradioimmunoassay).Setting—Cardiology department in a general hospital.Patients—128 consecutive eligible patients. Samples were collected for up to one year according to a prospective design: a subsection of 47 patients was selected for intensive study over the first 14 days. After one year, all available patients (67) were sampled on one further occasion.Results—Antibody responses to streptokinase and anistreplase were similar. Streptokinase resistance titres exceeded pretreatment concentrations five days after dosing, and values peaked at 14 days. By 12 months after dosing, 92% of resistance titres (n = 84) had returned to within the pretreatment range. Antistreptokinase IgG concentrations also exceeded baseline concentrations within five days and peaked at 14 days. Half of the individual values had returned to within the pretreatment range by 12 months (n = 84) and 89% by 30 months (n = 18).Conclusion—Although we cannot be sure of the clinical significance, because of the increased likelihood of resistance due to antistreptokinase antibody, streptokinase and anistreplase may not be effective if administered more than five days after an earlier dose of streptokinase or anistreplase, particularly between five days and 12 months, and increased antistreptokinase antibody may increase the risk of allergic-type reactions.     

An angiographic study of intracoronary streptokinase versus intravenous tissue plasminogen activator after failed coronary thrombolysis with intravenous streptokinase

Objective The medical treatment of failed intravenous streptokinase in patients with acute transmural myocardial infarction using angiographic endpoints.Design Prospective open angiographic comparison of intracoronary streptokinase with intravenous tissue plasminogen activator. Setting: Single center study in a tertiary institution.Subjects Eighty-five patients with acute myocardial infarction within 4 hours after symptom onset. Treatment regimens: The subjects received 1.5 million U intravenous streptokinase. Coronary angiography within 48 hours (median 19 hours) showed infarct-related vessel patency in 65 patients (76%). In the catheterization laboratory the 20 patients (24%) with failed intravenous streptokinase received repeat thrombolysis immediately after angiography. The first 10 patients with failed intravenous streptokinase received intracoronary streptokinase at a dose of 4000 U/min in the occluded infarctrelated artery for a maximum of 1 hour. The subsequent 10 patients received high-dose front-loaded intravenous tissue plasminogen activator (100 mg in 1 hour).Results In none of the patients receiving repeat streptokinase was reperfusion obtained. In 6 of 10 (60%) of the patients receiving tissue plasminogen activator, reperfusion was seen within 60 minutes (p < 0.005 vs. intracoronary streptokinase). One patient (5%) died and two refused follow-up angiography. Seventeen (88%) patients underwent angiography 3 months later according to the protocol. Two patients showed a persistently reperfused infarct-related artery, three reoccluded, four spontaneously reperfused, and eight had a persistently occluded infarct-related artery. The left ventricular ejection fraction was slightly higher at 3 months, and there were no differences between the patients with open vessels (increase + 7.7 ± 5.8%) and those with persistently occluded vessels (increase +5.8 ± 6.8%)Conclusions Repeat thrombolysis after failed intravenous streptokinase can be achieved with front-loaded intravenous tissue plasminogen activator but not with intracoronary streptokinase. Although patient numbers are small and repeat thrombolysis was performed rather late, this study leads the way to affordable optimization of thrombolysis, which needs large-scale testing.     

Monitoring of streptokinase resistance titre in acute myocardial infarction patients up to 30 months after giving streptokinase or anistreplase and related studies to measure specific antistreptokinase IgG.

OBJECTIVE--To examine the induction of antistreptokinase antibodies after giving streptokinase or anistreplase to patients with acute myocardial infarction. DESIGN--Patients were randomly allocated to receive either 1.5 x 10(6) IU, streptokinase or 30U anistreplase in a double blind study. Blood samples were collected immediately before treatment and subsequently at intervals up to 30 months; plasma samples were assayed for streptokinase resistance titre (functional assay) and streptokinase binding by IgG (microradioimmunoassay). SETTING--Cardiology department in a general hospital. PATIENTS--128 consecutive eligible patients. Samples were collected for up to one year according to a prospective design: a subsection of 47 patients was selected for intensive study over the first 14 days. After one year, all available patients (67) were sampled on one further occasion. RESULTS--Antibody responses to streptokinase and anistreplase were similar. Streptokinase resistance titres exceeded pretreatment concentrations five days after dosing, and values peaked at 14 days. By 12 months after dosing, 92% of resistance titres (n = 84) had returned to within the pretreatment range. Antistreptokinase IgG concentrations also exceeded baseline concentrations within five days and peaked at 14 days. Half of the individual values had returned to within the pretreatment range by 12 months (n = 84) and 89% by 30 months (n = 18). CONCLUSION--Although we cannot be sure of the clinical significance, because of the increased likelihood of resistance due to antistreptokinase antibody, streptokinase and anistreplase may not be effective if administered more than five days after an earlier dose of streptokinase or anistreplase, particularly between five days and 12 months, and increased antistreptokinase antibody may increase the risk of allergic-type reactions.