Treatment of acute myocardial infarction with anisoylated plasminogen streptokinase activator complex.

Abstract

A controlled trial in 149 patients admitted to a district hospital with probable myocardial infarction tested the effect of 30 units of anisoylated plasminogen streptokinase activator complex (APSAC) on indices of infarct size. Patients were grouped prospectively according to whether they entered the trial within two and a half hours (early entry) or between two and a half and four hours (late entry) after onset ofthe symptoms. Sixty seven of 73 patients in the control group showed increased plasma activity of myocardial creatine kinase isoenzyme that was diagnostic of infarction compared with only 60 of 76 who received APSAC. The difference was significant overall but occurred predominantly in the early entry group. The patients who received APSAC had more early ventricular arrhythmias, compatible with reperfusion, and showed greater preservation of R waves during admission to hospital. Unwanted effects were generally minor and more common in the actively managed group than the control group (26% v 3%). After nine to 12 months offollow up 12 patients in the control group had died compared with seven in the actively managed group.The ease of administration and the apparent efficacy of APSAC suggest that it is suitable for use in a district hospital for patients with suspected acute myocardial infarction. IntroductionThrombus obstructing an atherosclerotic artery is the commonest precipitating cause of acute transmural myocardial infarction.' 2 When intravenous streptokinase was introduced nearly 30 years ago it seemed a logical treatment to use early in an attack; the first paper on this was published in 1959.3 Although early results were promising,45 subsequent studies, including Australian and British multicentre trials,"7 did not show any evidence of benefit from this treatment, and it was not used much outside mainland Europe.The intracoronary administration of streptokinase was associated with cineangiographic evidence of reperfusion, and this led to a resurgence of interest.-" Relatively few patients, however, can be admitted to hospitals that have facilities for immediate coronary angiography. Moreover, a recent review of published data on the influence of thrombolytic treatment on mortality does not support the belief that intracoronary administration is superior to intravenous administration.'2 Efficacy and safety may be enhanced by fibrin specific agents that become concentrated at the site of a recent thrombus, thus improving the ratio of local effect to systemic effect. These agents include tissue plasminogen activator," 14 prourokinase," and anisoylated plasminogen streptokinase activator complex (APSAC or BRL 26921).'

Early thrombolytic treatment in acute myocardial infarction: reappraisal of the golden hour

“…These trials were reported between 1983 and 1993 and indexed in the MEDLINE information system. 24 There are 22 such trials 12,13,[25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44] The indication for fibrinolytic therapy in two of the trials may not have been appropriate: the USIM trial included a high proportion (32%) of patients with unstable angina, and the ISIS-3 uncertain indication group consisted of patients without or with only minor ST elevation; 43,44 these patient subgroups are unlikely to benefit from fibrinolysis. [45][46][47] The USIM and ISIS-3 trials included 4250 patients who were treated within 3 h of symptom onset and may therefore seriously bias benefit estimations for early treatment of those with confirmed infarction.…”

Acylated Plasminogen‐Streptokinase Activator Complex: A New Approach to Thrombolytic Therapy

“…Significant ventricular arrhythmias occurred in 15 of 16 patients treated with anistreplase versus 13 of 18 controls in one They also occurred sooner after treatment: 142 versus 422 minutes.38 In another study, arrhythmias in the first 6 hours after treatment were more common with anistreplase than with placebo.30 Early ventricular tachycardia was significantly more frequent in anistreplase-treated patients than in controls (63% vs 37%; p < 0.05). 39 This was also confirmed using heparin-treated patients as a control group, again demonstrating a significant difference (48% vs 29%; p 0.002).= The earlier occurrence of arrhythmias with anistreplase may in fact signal earlier resolution of myocardial infarction.…”

“…The studies determined that anistreplase demonstrates a patency rate equivalent to that of intracoronary SK (51 % vs 60%). 16 In comparison to placebo or in open studies, anistreplase demonstrated earlier resolution of electrocardiographic (ECG) abnormalities, earlier peak enzyme release, and earlier occurrence of arrhythmia^.^^, 38,39 Two studies assessed the use of anistreplase before hospitalization; that is, patients were evaluated at home and received the drug from a mobile intervention team. Of 13 patients, 10 were considered treatment successes as assessed by noninvasive values of pain relief, and return to normal of ECG and reperfusion arrhythmia^.^^ Sixteen of 21 evaluable patients had clinical or ECG evidence of reperfusion within 2 hours of treatment.4' Patency was confirmed by angiography in 14 of the 16.…”

Development of Anisoylated Plasminogen-Streptokinase Activator Complex from the Acyl Enzyme Concept

“…When data are pooled 29 from studies for patients who had patent coronary arteries 90 minutes after dosing and who were inves tigated further by angiography 1 to 3 days later, reocclusion was found to have occurred in 4% in those patients receiving APSAC by comparison with 10% for SK. Other types of clinical trial have begun to ex amine the response to APSAC in a district hospital setting 36 and when administered before admission of patients to the hospital, in a mobile care unit. 37 For both types of trials the results are encouraging and provide support to the initiation of widespread use of APSAC.…”