Streptokinase In Acute Myocardial Infarction Research Articles

Humoral and cellular immune responses up to 7.5 years after administration of streptokinase for acute myocardial infarction.

Administration of streptokinase results in an immunological response which may lead to increased risk of anaphylactic reaction or reduced thrombolytic efficacy on repeat administration. For these reasons current recommendations suggest that streptokinase should not be given up to 1 year after first administration. We sought to define the profile of both the circulating antibody and T-cell response to streptokinase in patients who had received streptokinase up to 7.5 years previously following acute myocardial infarction. Neutralizing anti-streptokinase antibody and total anti-streptokinase IgG were measured in 219 patients who had suffered acute myocardial infarction between 12 and 90 months previously and had received streptokinase. T-cell response to streptokinase was assessed by in-vitro proliferation of peripheral blood mononuclear cells (n=234). Data on all parameters were available in 184 patients. Controls (n=22) had suffered acute myocardial infarction between 73 and 84 months previously but had not received thrombolytic therapy. Compared to controls, anti-streptokinase antibodies were elevated at all time periods from 12 to 90 months after streptokinase treatment. Total anti-streptokinase titres showed the expected correlation with neutralizing anti-streptokinase antibodies (P<0.0001). Peripheral blood mononuclear cells showed a vigorous in-vitro proliferative response to streptokinase 6 days after treatment (P=0.05 vs pre-treatment), but this was not detectable at 6 weeks or subsequently. There is as yet no evidence of a time limit beyond which administration of streptokinase on a second occasion can be regarded as safe and likely to be effective. Measurement of neutralizing anti-streptokinase or total anti-streptokinase IgG titre appear to provide equivalent information regarding the antibody status of a population. Further studies are required regarding the apparent lack of peripheral blood mononuclear cells responsiveness in patients previously exposed to streptokinase.

Thrombolysis with saruplase versus streptokinase in acute myocardial infarction: Five-year results of the PRIMI Trial

Background Short-term safety and efficacy of thrombolysis with saruplase in acute myocardial infarction have been shown in several trials. To assess long-term outcome of patients treated with saruplase or streptokinase for myocardial infarction, a 5-year follow-up of patients included in the Pro-Urokinase in Myocardial Infarction Trial was performed. Methods and Results Follow-up data are available from 8 centers on 255 (92.4%) of 276 included patients. The 5-year mortality rate was comparable with 20.8% of patients in the saruplase group and 16.9% in the streptokinase group (odds ratio 1.29, 95% confidence interval 0.69 to 2.42). In both groups, a considerable number of fatal cardiovascular events occurred more than 1 year after study inclusion. Rates of percutaneous transluminal coronary angioplasty and coronary artery bypass grafting were comparable in both groups. Reinfarction within 5 years occurred in 19.0% of patients in the saruplase group and tended to be less frequent at 10.8% after streptokinase treatment (odds ratio 1.94, 95% confidence interval 0.98 to 3.84). In both groups, the majority of reinfarctions took place more than 3 months after study inclusion. The 5-year stroke rate was 3.6% and 7.2% in the saruplase and streptokinase groups, respectively (odds ratio 0.49, 95% confidence interval 0.16 to 1.47). Subjective symptoms of heart failure and angina pectoris were comparable in both groups. Conclusions Our data are consistent with a similar long-term outcome for patients treated with saruplase or streptokinase. Despite the low-risk profile of the patient cohort, there were considerable adverse event rates over a 5-year period. (Am Heart J 1999;138:518-24.)

Streptokinase antibodies inhibit reperfusion during thrombolytic therapy with streptokinase in acute myocardial infarction.

To evaluate the influence of pretreatment IgG against streptokinase on the outcome of streptokinase treatment in acute myocardial infarction. Coronary care unit. From 88 patients admitted to the coronary care unit due to chest pain, blood samples were taken for determination of the pre-existing titre of antibodies against streptokinase. The patients were treated and monitored according to standard protocols. Fifty of the patients received thrombolytic therapy with streptokinase due to acute myocardial infarction and were monitored with continuous dynamic vectorcardiography, making possible the continuous analysis of ST- and QRS-vector changes and determination of the event of reperfusion. None of these 50 patients had been given streptokinase therapy previously. According to the vectorcardiographic criteria 21(42%) patients had signs of early (within 2 h) reperfusion after streptokinase therapy. These patients had lower pre-existing antibody titres than patients without signs of reperfusion (mean values 0.20 and 0.45 arbitrary units, P = 0.01). None of the patients with a titre higher than 0.50 arbitrary units (nine patients) had signs of early reperfusion. Of the 41 patients with a titre lower than 0.50 arbitrary units 52.5% had signs of early reperfusion. The present investigation indicates that pre-existing streptokinase antibodies play an important role in reperfusion failure during thrombolytic therapy with streptokinase in acute myocardial infarction. Therefore, the determination of streptokinase antibodies may differentiate between those patients who may benefit from streptokinase treatment and those who should be treated with some other regime.

Usefulness of the presenting electrocardiogram in predicting successful reperfusion with Streptokinase in acute myocardial infarction

The presenting electrocardiogram may contain information indicating the probability of successful reperfusion. The relation between 3 parameters in the presenting electrocardiogram (pathologic Q waves, T-wave inversion, and the slope of ST elevation) and Thrombolysis in Myocardial Infarction trial (TIMI) grade 3 flow in the infarct-related artery was assessed angiographically 90 minutes after beginning streptokinase in 362 patients. TIMI grade 3 flow was more common in patients without Q waves (55%) than in those with Q waves (35%; p <0.001), and more common in patients without T-wave inversion (50%) than in those with T-wave inversion (30%; p <0.002). There was no relation between the slope of the ST segment or the magnitude of its deviation and the achievement of TIMI grade 3 flow. Only 20% of the 59 patients with both Q waves and T-wave inversion had TIMI grade 3 flow, compared with 50% of the remaining patients (p <0.0001). Among patients treated within 3 hours, TIMI grade 3 flow was seen in 68% of those without versus 44% of those with Q waves (p <0.01), and in 62% of those without versus 43% of those with T-wave inversion (p = 0.06). Among patients treated after 3 hours, TIMI grade 3 flow was seen in 38% of those without versus 30% of those with Q waves (p = NS), and in 38% of those without versus 23% of those with T-wave inversion (p <0.05). On multivariate analysis, the absence of Q waves, the time from the onset of chest pain to treatment, and age were independent predictors of TIMI grade 3 flow. Pathologic Q waves in the presenting electrocardiogram provide valuable information as to the probability of achieving successful reperfusion following administration of streptokinase, and may be helpful for triage of patients to alternative reperfusion strategies, including percutaneous revascularization.

Coronary Thrombolysis

The clinical description of acute myocardial infarction (AMI) by Herrick 1 Herrick JB. Clinical features of sudden obstruction of the coronary arteries. JAMA. 1912; 59: 2015-2020 Crossref Google Scholar in 1912 embodied the concept that acute coronary thrombosis was responsible, and this view was widely adopted. The first trial of IV administration of thrombolytic therapy was published in 1959 2 Fletcher AP Sherry S Alkjaersig N et al. The maintenance of a sustained thrombolytic state in man: II. Clinical observations on patients with myocardial infarction and other thromboembolic disorders. J Clin Invest. 1959; 38: 11-19 Google Scholar and the first of intracoronary use was published in I960. 3 Boucek HJ Murphy WP. Segmental perfusion of the coronary arteries with fibrinolysin in man following a myocardial infarction. Am J Cardiol. 1960; 5: 525-533 Abstract Full Text PDF Google Scholar Over the next 25 years, 24 randomized studies of IV thrombolytic therapy were conducted, primarily in Europe, 4 Yusuf S Collins R Peto R et al. Intravenous and intracoronary fibrinolytic therapy in acute myocardial infarction: overview of results on mortality, reinfarction and side effects from 33 randomized controlled trials. Eur Heart J. 1985; 6: 556-585 PubMed Google Scholar the results varying from statistically significant benefit to no suggestion of benefit, and thrombolytic therapy was rarely used. In the late 1970s, there was a reawakening of interest in thrombolytic therapy for AMI, initially directed at intracoronary administration. 5 Chazov EL Mateeva LS Mazaer AV et al. Intracoronary administration of fibrinolysis in acute myocardial infarction. Ter Arkh. 1976; 48: 8-19 PubMed Google Scholar ,6 Rentrop KP Blanke H Karsch KR et al. Selective intracoronary thrombolysis in acute myocardial infarction and unstable angina pectoris. Circulation. 1981; 63: 307 Crossref PubMed Google Scholar The reality that most hospitals do not have cardiac catheterization laboratories and the recognition of the economic and logistic impediments to emergency cardiac catheterization, even in referral hospitals, stimulated a reevaluation of IV thrombolytic therapy. 7 Schroeder R Biamino G Leitner E-R et al. Intravenous short-term infusion of streptokinase in acute myocardial infarction. Circulation. 1983; 67: 536-548 Crossref PubMed Google Scholar ,8 Lo YSA. Intravenous versus intracoronary streptokinase in acute myocardial infarction. Clin Cardiol. 1985; 8: 609-619 Crossref PubMed Google Scholar

P18 Enoxaparin and accelerated streptokinase in acute myocardial infarction (CLEXAS study)

P18 Enoxaparin and accelerated streptokinase in acute myocardial infarction (CLEXAS study)

P19 The romanian multicentric study for accelerated streptokinase in acute myocardial infarction (ROMAS 1 study)

P19 The romanian multicentric study for accelerated streptokinase in acute myocardial infarction (ROMAS 1 study)

Estimation of enzymatic infarct size: Direct comparison of the marker enzymes creatine kinase and α-hydroxybutyrate dehydrogenase

Background Estimation of infarct size with serum-time activity curves of creatine kinase (CK) (or CKMB) or α-hydroxy- butyrate dehydrogenase (HBDH) is widely used in clinical trials. However, an independent variable such as left ventricular function has not been directly compared with CK and HBDH infarct size measurements in the same group of patients. Methods and Results Infarct size was calculated by the CK area under the curve (AUC) and by the cumulative release of HBDH in 90 patients with acute myocardial infarction undergoing early thrombolysis. Infarct size estimates by CK AUC and HBDH release were closely correlated ( r = 0.88, p < 0.0001). HBDH release was significantly better ( p < 0.001) correlated to angiographically assessed ejection fraction 8 days after infarction ( r = 0.74) than to CK AUC ( r = 0.60), as was maximum HBDH ( r = 0.71) compared with CK maximum ( r = 0.59). In contrast to CK, maximum levels of HBDH only slightly overestimate myocardial damage in patients with early reperfusion. Data reanalyzed from the former placebo-controlled Intravenous Streptokinase in Acute Myocardial Infarction (ISAM) study revealed significant differences in favor of streptokinase for CK and CKMB AUC and for HBDH maximum, but no difference for CK and CKMB maximums. Conclusions For comparative clinical trials HBDH appears to be the preferable marker enzyme for estimates of infarct size and measure of reperfusion effectiveness. In clinical practice one routine measure of HBDH serum activity on the second day after infarction may be a useful approximate value of infarct size. (Am Heart J 1998;135:1-9.)

Activation of the contact phase of the coagulation, of the kinin system and of the complement cascade by streptokinase in acute myocardial infarction

Summary Thrombolytic therapy in acute myocardial infarction is a widely-accepted and life-saving therapy. However, it is hampered by a considerable recocclusion rate. Furthermore, hypotensive reactions are frequently observed, especially if the non clot-specific thrombolytic agent streptokinase is used. Streptokinase increases the pre-existing elevation of thrombin generation in these patients and also activates the factor XII-contact phase system. Increase of the plasma kallikrein activity and an enhanced bradykinin generation, probably caused by the plasminemia, were described. These changes after streptokinase infusion are paralleled by an activation of the complement cascade. Activation of the coagulation cascade and of the kallikrein-kinin system by streptokinase might be one of the reasons for coronary reocclusions after initially successful thrombolytic therapy in patients with acute myocardial infarction. Side-effects of bradykinin generation as hypotensive reactions were also observed after streptokinase infusion. These side-effects might become more important in the future with increasing use of ACE-inhibiting drugs in patients with coronary heart disease.

Significance of initial ST segment changes for thrombolytic treatment in first inferior myocardial infarction.

OBJECTIVE: To evaluate the benefit to risk ratio of thrombolytic treatment in patients with small inferior acute myocardial infarction (AMI). Controlled studies relating the benefit from thrombolysis with initial electrocardiographic...

Pericardial effusion after streptokinase for acute myocardial infarction: an echocardiographic 1-year follow-up study.

Since the reported incidence of pericardial effusion following thrombolysis is highly variable, we have evaluated 80 consecutive patients with first acute myocardial infarction treated with streptokinase. Two-dimensional echocardiographic studies were performed on days 1, 2, 3, and 7, at 3 and 6 weeks, and 3, 6, and 12 months following acute myocardial infarction. Throughout the study, pericardial effusion was found in 7 of 80 (8.75%) patients, being small in 5 patients, moderate in 1, and large in 1 patient. No clinical, angiographic, or echocardiographic variable was associated with pericardial effusion formation. The incidence of pericardial effusion found in our study is almost three times lower than in other echocardiographic studies on pericardial effusion in thrombolysed patients. Whether this differences results from the beneficial effects of streptokinase is not clear.

Tissue-plasminogen activator reduced mortality rates compared with streptokinase for acute myocardial infarction

Tissue-plasminogen activator reduced mortality rates compared with streptokinase for acute myocardial infarction

Randomized, double blind comparison of reteplase double bolus administration with streptokinase in acute myocardial infarction (inject): Trial to investigate equivalence: International Joint Efficacy Comparison of Thrombolytics The Lancet, Vol. 346, pp. 329–335

Randomized, double blind comparison of reteplase double bolus administration with streptokinase in acute myocardial infarction (inject): Trial to investigate equivalence: International Joint Efficacy Comparison of Thrombolytics The Lancet, Vol. 346, pp. 329–335

Anti-streptokinase antibodies and streptokinase resistance in an Aboriginal population in northern Australia.

Thrombolytic treatment with streptokinase in acute myocardial infarction has proven to be safe and effective in Caucasian populations with relatively low levels of anti-streptokinase IgG and streptokinase resistance. Higher levels of antibodies, as seen in previous recipients of streptokinase therapy, cause more adverse reactions and may result in lower efficacy. To examine the levels of anti-streptokinase IgG and streptokinase resistance in a population subjected to endemic streptococcal infections. Thirty Aboriginal adults from a remote community in Northern Australia with endemic streptococcal infections and 15 non-Aboriginal adults from an urban community without endemic infections participated in this study. Aboriginal adults exhibited levels of anti-streptokinase IgG and streptokinase resistance that, respectively, were almost 20 and 15 times greater than the values of non-Aboriginal adults. At least 23% of Aboriginal adults had sufficiently high levels of streptokinase resistance to neutralise a standard 1.5 million unit dose of streptokinase. Aboriginal adults from a remote community had dramatically elevated levels of anti-streptokinase IgG and in vitro streptokinase resistance. Prospective studies are needed to assess the clinical relevance of streptokinase resistance in populations from areas with endemic streptococcal infection.

Costs and survival were higher for acute MI treated with t-PA compared with streptokinase

Source Citation Mark DB, Hlatky MA, Califf RM, et al. Cost effectiveness of thrombolytic therapy with tissue plasminogen activator as compared with streptokinase for acute myocardial infarction. N ...

Randomised, double-blind comparison of reteplase double-bolus administration with streptokinase in acute myocardial infarction (INJECT): trial to investigate equivalence: International Joint Efficacy Comparison of Thrombolytics

Summary Streptokinase and alteplase are established therapies in acute myocardial infarction. Reteplase is a new thrombolytic agent that can be given as a double bolus. This trial was designed to determine whether the effect of reteplase on survival was at least equivalent (within 1% of fatality rate) to that of a standard streptokinase regimen. Patients from 208 centres in nine countries (n=6010) with symptoms and electrocardiographic criteria consistent with acute myocardial infarction were randomised to receive double-blind either streptokinase 1·5 MU intravenously over 60 min or reteplase two boluses of 10 MU given 30 min apart. Treatment could be started up to 12 h from onset of symptoms. All patients received intravenous heparin for at least 24 h. The primary endpoint was 35-day outcome. There were 270 deaths (9·02%) in the reteplase and 285 deaths (9·53%) in the streptokinase group, a non-significant difference (95% Cl -1·98% to 0·96%). Among patients who received treatment (98·8%) there were 263 deaths (8·90%) in the reteplase compared with 279 deaths (9·43%) in the streptokinase group (a difference of -0·53%). Because the upper limit of the 90% Cl for this difference is 0·71%, this result shows that reteplase is at least as effective as streptokinase. In-hospital stroke rates were 1·23% for reteplase and 1·00% for streptokinase. Bleeding events were similar in the two treatment groups (0·7% reteplase, 1·0% streptokinase). The incidence of recurrent myocardial infarction was similar, but there were significantly fewer cases of atrial fibrillation, asystole, cardiac shock, heart failure, and hypotension in the reteplase group. We conclude that reteplase is an effective drug in the treatment of acute myocardial infarction. It is clinically safe, its administration is simple, and it will be a useful addition to the range of thrombolytic agents available.

Cost Effectiveness of Thrombolytic Therapy with Tissue Plasminogen Activator as Compared with Streptokinase for Acute Myocardial Infarction

Cost Effectiveness of Thrombolytic Therapy with Tissue Plasminogen Activator as Compared with Streptokinase for Acute Myocardial Infarction

725-4 Late Survival Following Early Coronary Intervention After Fibrinolytic Therapy with Streptokinase in Acute Myocardial Infarction (Results of a randomized trial: SIAM-I)

324 pts with acute myocardial infarction were treated with intravenous Streptokinase (&lt;4 hrs after onset of symptoms, 1.500.000 U/1 hr) in 13 acute care hospitals and were centrally randomized by phone call to the university hospital in two groups during fibrinolysis. (invasive strategy) CA with PTCA/CABS 14 to 48 hours after start of treatment and predischarge control CA. (control group) no CA within the first 21 days, unless there is evidence for ischemia and predischarge control CA. In Gr-A 14/158 (=9%) pts, in Gr-B 10/166 (=6%) pts died before hospital discharge (n.s.). In a follow-up period of at least 24 months (Median 35 months) 13/144(=9%) pts of Gr-A and 14/156 (=9%) pts of Gr-B died (n.s.). All other patients (n = 273; Gr-A: 131, Gr-B: 142) were followed for a median time of 76 months (30–89 months, 1723 patient years). In Gr-A 20/131 (= 15%) pts and in Gr-B 7/142 (=5%) pts died during this period (p &lt; 0.008). Cumulative number of deaths in Gr-A and Gr-BTimeGr-AGr-Bp-value&lt;14 hrs3 (=2%)3 (=2%)n.s.14–48 hrs9 (=6%)8 (=5%)n.s.in-hospital14 (=9%)10 (=6%)n.s.3-year-FU27 (=17%)24 (=14%)n.s.6-year-FU47 (=30%)31 (=19%)&lt;0.03 This data exclude even a long-term superiority of an invasive approach to patients with fibrinolytic treated acute myocardial infarction. A detailed stratification to identify patients who will benefit from coronary intervention is needed.

Human Anti-Streptokinase Antibodies Induce Platelet Aggregation in an Fc Receptor (CD32) Dependent Manner

Exposure to streptokinase (SK) elicits anti-SK antibodies (Abs), which inhibit fibrinolysis and induce platelet aggregation. The mechanism of the latter is not fully understood, although it seems to involve platelet binding by a plasminogen streptokinase and anti-SK ternary complex. Anti-SK Abs were purified by affinity chromatography from serum of patients having received SK for acute myocardial infarction (AMI), and were shown to be of the IgG type. Their effects were studied with (i) human platelets in citrated plasma in the presence of SK or acetylated plasminogen-SK activator complex (APSAC), and (ii) in washed platelets, resuspended in Tyrode buffer after lowering the ionic strength, in the presence of APSAC (which provides both SK and plasminogen). An antibody concentration-response curve was obtained, showing a plateau in the presence of 0.1 mg/ml IgG. By increasing the concentration of APSAC, we obtained a unimodal response curve, the optimal concentration of APSAC being 0.05 U/ml. Aggregation was suppressed by chelating calcium with EDTA, blocking fibrinogen binding by the synthetic peptide Arg-Gly-Asp-Ser (RGDS), and raising intraplatelet cAMP with Iloprost (a prostacyclin analogue). Aggregation required the interaction of the anti-SK Ab Fc domain with the platelet Fc-gamma receptor type II, also known as CD32, since: (i) it was blocked by the monoclonal antibody IV-3 directed against CD32, (ii) it did not occur with F(ab)'2 fragments, which block the response to the intact IgG. The clinical relevance of these platelet-activating anti-SK antibodies remains to be determined.(ABSTRACT TRUNCATED AT 250 WORDS)

“Rescue” thrombolysis with intracoronary tissue plasminogen activator for failed intravenous thrombolysis with streptokinase for acute myocardial infarction

Rescue thrombolysis appears to be safe and may be an alternative to angioplasty when normal epicardial blood flow is not achieved after administration of thrombolytic therapy in patients with acute myocardial infarction. Further trials are required to evaluate this approach.