Anisoylated Plasminogen Streptokinase Activator Complex Group Research Articles

A randomized factorial trial of reperfusion strategies and aspirin dosing in acute myocardial infarction

The focus of new research efforts to improve the morbidity and mortality associated with acute myocardial infarction (AMI) has turned to adjuvant agents that show promise of improving outcomes following coronary thrombolysis. We enrolled 162 patients with AMI in a randomized trial comparing front-loaded tissue-plasminogen activator (t-PA) plus weight-adjusted heparin with anisoylated plasminogen streptokinase activator complex (APSAC) without heparin as well as standard-dose (325 mg) and low-dose (81 mg) aspirin. The primary end point was an in-hospital morbidity profile; secondary end points were clinical and angiographic potency and hemorrhagic events. Selected sites performed an electrocardiographic substudy to determine the time to 50% ST-segment recovery and the time to steady state. Although the trial was terminated when the Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries-I trial showed that t-PA had a significant mortality advantage over streptokinase, important trends were evident. Patients given t-PA and heparin were better anticoagulated (p = 0.001), yet AP-SAC-treated patients had more bleeding complications. The primary end point favored t-PA (25.4% vs 31.3%), and the secondary end points were similar in both groups. In the electrocardiographic substudy, the t-PA group achieved both 50% ST-segment recovery and steady-state recovery sooner than the APSAC group. Patients taking low-dose aspirin had lower in-hospital mortality and less recurrent ischemia but more strokes than the standard-dose aspirin group. Thus, this trial demonstrated trends favoring front-loaded t-PA with weight-adjusted heparin over APSAC without heparin in the treatment of AMI. The use of low-dose aspirin did not appear to impose a loss of protection from adverse events, nor did standard-dose aspirin increase serious bleeding.

Increased survival after APSAC: 30-day and 12-month mortality data from the APSAC Intervention Mortality Study

Preliminary analysis of mortality data from the anisoylated plasminogen streptokinase activator complex (APSAC) Intervention Mortality Study (AIMS) showed a 47% reduction in 30-day mortality (with a 95% confidence interval of 21 to 65%) for patients treated with APSAC within 6 hours of onset of acute myocardial infarction. After follow-up of 1,004 patients for 30 days after randomization in the double-Mind, placebo-controlled, clinical trial, researchers found that 61 patients (12.2%) in the placebo group had died compared with 32 patients (6.4%) in the APSAC group (p = 0.0016). Incomplete follow-up of these patients for 1 year provided an estimated mortality of 19.4% in the placebo group and 10.8% in the APSAC group (log-rank test for survival to year p = 0.0006). Benefit was seen irrespective of age, site of infarction and time from onset of symptoms up to 6 hours.

Pharmacokinetics, thrombolytic efficacy and hemorrhagic risk of different streptokinase regimens in heparin-treated acute myocardial infarction

The systemic activator activity of 4 streptokinase (SK) regimens (250,000 IU intracoronary, group A; 500,000 IU, group B; 1.5 × 10 6 IU, group C; and 30 U anisoylated plasminogen streptokinase activator complex (APSAC) intravenously, group D) was tested with the fibrin plate technique. One hour after initiation of treatment, the activator activity was highest after APSAC (3.6 ± 0.9 U), slightly but not significantly less after SK 1.5 × 10 6 IU (3.0 ± 0.7), and significantly less after SK 500,000 IU (1.6 ± 0.5) and 250,000 IU (0.6 ± 0.5), p < 0.001. After SK, activator activity half-lives were 184 minutes (group B) and 169 minutes (group C), and after APSAC 188 minutes (group D). These were all in agreement with > 12 hour duration of changes in other markers of systemic fibrinolysis (euglobulin lysis time) and substrates depletion (fibrinogen, plasminogen, α 2 antiplasmin). In extended pilot clinical groups given identical thrombolytic regimens during full anticoagulation with heparin, angiographic coronary patency was found in 83% (35 of 42) after intracoronary SK (group 1), in 73 and 75%, respectively, after 500,000 IU (31 of 43) and 1.5 × 10 6 IU (30 of 40) (group 2 and 3, difference not significant) and 80% (8 of 10) after the 30-U bolus of APSAC (group 4). The overall hemorrhagic risk was 24%, equally distributed among the 4 regimens and mostly (91%) related to catheters. The incidence of bleeding unrelated to vessel puncture was 4%; no deaths occurred. It is concluded that APSAC is the most fibrinolytic regimen but its potential thrombolytic superiority over SK remains to be demonstrated. The amount of activator produced by 500,000 IU SK was less than after 1.5 × 10 6 IU, but yielded to the same thrombolytic efficacy. This indicates that an optimal amount is probably below 1 × 10 6 IU. Heparin before and during treatment with thrombolytics is feasible but its value should be assessed prospectively.

Multicenter trial of intravenous Anisoylated Plasminogen Streptokinase Activator Complex (APSAC) in acute myocardial infarction: Effects on infarct size and left, ventricular function

Two hundred thirty-one patients with a first acute myocardial infarction were randomly allocated within 5 h after the onset of symptoms either to treatment with anisoylated plasminogen streptokinase activator complex (APSAC), 30 U over 5 min, or to conventional heparin therapy, 5,000 IU in a bolus injection. Heparin was reintroduced in both groups 4 h after initial therapy at a dosage of 500 IU/kg per day. One hundred twelve patients received APSAC and 119 received heparin within a mean period of 188 ± 62 min after the onset of symptoms. Both groups were similar in age, location of the acute myocardial infarction, Killip functional class and time of randomization. Elective coronary arteriography was performed on an average of 4 ± 1.2 days after initial therapy.Follow-up radionuclide angiography and thallium-201 single photon emission computed tomography were performed before hospital discharge. Infarct size was estimated from single photon emission computed tomography and expressed as a percent of total myocardial volume. The patency rate of the infarct-related artery was 77 % in the APSAC group and 36% in the heparin group (p < 0.001). Left ventricular ejection fraction determined from contrast angiography was significantly higher in the APSAC group than in the heparin group. This was true for the entire study group (0.53 ± 0.13 versus 0.47 ± 0.12; p = 0.002) as well as for the subgroups of patients with anterior and inferior wall infarction (0.47 ± 0.13 versus 0.40 ± 0.11; p = 0.04 and 0.56 ± 0.10 versus 0.51 ± 0.11; p = 0.02, respectively). At 3 weeks, the difference remained significant for the anterior myocardial infarction subgroup. A significant 31% reduction in infarct size was found in the APSAC group (33% for the anterior infarction subgroup [p < 0.05] and 16% for the inferior infarction subgroup [p = NS]). A close inverse relation was found between the values of left ventricular ejection fraction and infarct size (r = −0.73, p < 0.01). By the end of a 3 week follow-up period, seven APSAC-treated patients and six heparintreated patients had died.In conclusion, the early infusion of APSAC in acute myocardial infarction produced a high early patency rate, significant limitation of infarct size and significant preservation of left ventricular systolic function, mainly in anterior wall infarction.

The German multicenter trial of anisoylated plasminogen streptokinase activator complex versus heparin for acute myocardial infarction

A multicenter randomized trial of anisoylated plasminogen streptokinase activator complex (APSAC) versus heparin in patients with acute myocardial infarction of < 4 hours' duration was undertaken in 19 hospitals. Of the 313 patients, 151 received heparin and 162 APSAC (30 U as intravenous injection). Within 28 days of hospital stay, 19 deaths (12.6%) occurred in the heparin group and 9 deaths (5.6%) in the APSAC group (p = 0.032). After 24 hours, patients in the APSAC group had a significantly lower incidence of cardiogenic shock (3.2 vs 9.5%, p = 0.031), asystole (3.8 vs 10.8%, p = 0.015) and need for resuscitation (5.1 vs 11.5%, p = 0.039). There was no difference in global and infarct-related ejection fraction between the 2 groups. Thus, APSAC favorably influences prognosis and clinical course in hospital.

Comparison of intravenous anisoylated plasminogen streptokinase activator complex and intracoronary streptokinase in acute myocardial infarction

Coronary angiography was used to compare the efficacy of anisoylated plasminogen streptokinase activator complex (APSAC) administered intravenously and streptokinase given by intracoronary infusion in inducing reperfusion in patients with a proven acute myocardial infarction. Forty-two patients received 30 U of APSAC intravenously over 5 minutes and 43 patients received 250,000 IU of streptokinase given via intracoronary infusion over 90 minutes, after occlusion of the infarct-related vessel was demonstrated by angiography. Reperfusion was achieved in 23 (64%) of 36 patients (mean time to reperfusion 46 minutes) treated with APSAC and 25 (67%) of 37 patients (mean time to reperfusion 45 minutes) treated with intracoronary streptokinase, who were angiographically evaluated 90 minutes after the start of treatment. Twenty-four hours after treatment, reocclusion had occurred in 1 (5%) of 22 patients in the APSAC group and in 3 (13%) of 23 patients in the streptokinase group. No major bleeding was observed in either treatment group despite a similar systemic lytic state that lasted for up to 48 hours. Two patients treated with APSAC died after severe left ventricular failure unrelated to therapy. The results indicate that APSAC given intravenously is as effective as streptokinase given intracoronary in producing thrombolysis in acute myocardial infarction. The major advantages of APSAC are its rapid and convenient administration by a single intravenous injection, the low rate of arterial reocclusion and good patient tolerance.

Anisoylated plasminogen streptokinase activator complex in acute myocardial infarction: A placebo-controlled arteriographic coronary recanalization study

Anisoylated plasminogen streptokinase activator complex (APSAC) is a new thrombolytic agent that is of interest because of its ease of administration as an intravenous bolus injection. This report describes the first double-blind, placebo-controlled evaluation of intravenous APSAC for coronary recanalization in acute myocardial infarction. Unequivocal documentation of recanalization was provided by coronary arteriography before and after the drug intervention. Forty patients with acute myocardial infarction underwent coronary arteriography 3.1 +/- 1.2 hours after the onset of symptoms. This demonstrated occlusion of the infarct-related coronary artery in 29 patients who were then randomized to treatment with intravenous APSAC, 30 mg (n = 16), and placebo (n = 13) 3.3 +/- 1.3 hours after the onset of symptoms. Repeat arteriography 90 minutes later demonstrated recanalization of the infarct-related coronary artery in nine patients who had received APSAC compared with only one patient who had received placebo (56 versus 8%, p less than 0.05). The 95% confidence limits for this 48% difference between the groups are 20 to 76%. Arteriography at 3 days showed persistent patency of all recanalized coronary arteries except one (APSAC group) and also showed late recanalization in another four patients, three of whom had received APSAC. In the patients who had a patent infarct-related coronary artery at the initial arteriographic study, patency was maintained throughout the study period regardless of whether the patient was randomized to APSAC (n = 4) or placebo (n = 7). Complications related to APSAC therapy were excessive bruising at the catheterization site in seven patients and minor sensitivity reactions in three.(ABSTRACT TRUNCATED AT 250 WORDS)

Treatment of acute myocardial infarction with anisoylated plasminogen streptokinase activator complex in a district hospital. Tolerance data.

Approximately 250 patients with probable myocardial infarction have been treated with anisoylated plasminogen streptokinase activator complex (APSAC) at the Royal Sussex County Hospital in Brighton. This report of tolerance and adverse effects in 200 of these patients, observed over 6 months, includes data from 149 patients treated in a controlled study reported by Ikram et ai. (1986). All patients received 30U of APSAC given intravenously over 4 or 5 minutes. Immediate allergic responses such as flushing, changes in pulse rate or blood pressure, or dyspnoea were all infrequent and mild. Eight to 12 days after treatment, vasculitic purpura occurred in 5 patients, but resolved spontaneously in 2 to 5 days. There were no serious disorders of renal function and no late sequelae. Bleeding is the most frequent complication of thrombolytic therapy. Seven patients had reductions in haemoglobin of 3g or more and 5 of them required transfusion. However, only 1 patient showed important haemodynamic effects. Two patients had showers of small peripheral emboli to the lower part of the body: 1 of these patients died. This may have been the result of partial thrombolysis of an aortic clot, but a similar syndrome was also seen in a patient who had not received a thrombolytic agent. Ventricular fibrillation was observed in 20/200 treated patients, which is the expected incidence in this unit for patients admitted within 4 hours of infarction. Only 5 cases of ventricular tachycardia required treatment. As no pretreatment angiography was performed, reocclusion rates could not be determined. However, non-fatal reinfarction occurred in only 3OJo of patients in the first 2 weeks and less than 7OJo by 6 months. During the 12-month follow-up of 149 patients included in the controlled study, 12 patients died in the control group compared with 7 in the APSAC group. This indicates that thrombolytic therapy with APSAC may reduce late mortality.

Analysis of Coagulation and Fibrinolysis after Intravenous Anisoylated Plasminogen Streptokinase Activator Complex or Heparin in Patients with Acute Myocardial Infarction

A multicentre randomised trial including 87 patients admitted for acute myocardial infarction compared the effects of a single intravenous bolus of an anisoylated plasminogen streptokinase activator complex (APSAC) 30 units with those of heparin treatment on haemostasis during the first 4 days after treatment. In the APSAC group, a rapid and significant reduction in fibrinogen, plasminogen and alpha 2-antiplasmin was observed, associated with an increase of fibrin(ogen) degradation products, reflecting a strong systemic lytic activity. None of these parameters were significantly modified by heparin, but the anticoagulant effect was apparent as assessed by the activated partial thromboplastin time. The systemic fibrinolysis induced after different regimens of streptokinase infusion demonstrated that an intravenous bolus of APSAC 30U was as potent as streptokinase 500,000 or 1,500,000IU administered intravenously over 45 minutes and definitely more fibrinolytic than intracoronary infusion of streptokinase 250,000IU. Despite the demonstrated fibrin specificity of the drug at a low dose, a high dose of APSAC (30U intravenously) induced an important systemic lytic state for at least 12 hours.

Safety and Tolerance Data from the Belgian Multicentre Study of Anisoylated Plasminogen Streptokinase Activator Complex versus Heparin in Acute Myocardial Infarction1

In the European Multicentre Study (EMS), the safety and efficacy of a single 30U intravenous injection of anisoylated plasminogen streptokinase activator complex (APSAC) was studied in patients with acute myocardial infarction. The present study discusses the Belgian data on safety and tolerance from the EMS study. 87 patients were randomised to treatment with APSAC or heparin. The reperfusion rate was 60.5% (APSAC) versus 20.5% (heparin control), and reocclusion occurred in 21% of the reperfused APSAC patients. Drug-related adverse events consisted of bleeding problems (7 events in patients on APSAC and 1 event in a patient on heparin and moderate allergic reactions (12 events in 9 patients on APSAC and 1 event in a heparin patient). There was 1 drug-related death in the APSAC group (hypovolaemic shock due to central vein puncture during lytic state) which could have been avoided. It is concluded that thrombolytic treatment of acute myocardial infarction with APSAC is effective and safe, as long as the standard precautions for thrombolytic treatment are respected. Bleeding and allergic-type events are infrequent, usually well tolerated and easily treated.