An interim report of the efficacy and safety of anisoylated plasminogen streptokinase activator complex (APSAC)

Abstract

Anisoylated plasminogen streptokinase activator complex (APSAC) is a thrombolytic agent which can be administered to patients with acute myocardial infarction by intravenous injection rather than prolonged infusion, and which has sustained fibrinolytic activity, inducing thrombolysis with a low risk of early rethrombosis. In clinical trials, APSAC 30U intravenously produced angiographically confirmed reperfusion in 86/156 patients (55%) and coronary patency (in the absence of pretreatment angiography) in 131/161 patients (81%) up to 90 minutes after treatment. These figures compared with a reperfusion rate of 65% (71/110 patients) for intracoronary streptokinase, and a patency rate of 53% (27/51 patients) with intravenous streptokinase. Reperfusion occurred at a mean of about 45 minutes after either APSAC or streptokinase, and APSAC was more effective when administered within 4 hours, than between 4 and 6 hours, after the onset of symptoms of infarction. Reocclusion occurred in 4% (3/80) of infarct-related arteries assessed angiographically 1 to 3 days after APSAC, compared with 10% (7/74) after streptokinase. Preliminary analysis of mortality data from studies involving APSAC suggests a trend towards improved survival with APSAC in comparison with conventional therapy. Among 1855 patients treated with APSAC, and observed for periods of 1 month to 1 year, there have been 115 deaths (6.2%). This compares with a mortality of 12.3% among patients receiving non-thrombolytic therapy (n = 708). The results of large controlled mortality studies are awaited before evaluation of the precise extent of improvement with APSAC can be made. APSAC has been associated with relatively few serious side effects. Analysis of case records for 834 patients who received APSAC 30U intravenously revealed at least 1 suspected side effect in 44%, compared with in 33% of placebo-treated patients (n = 138). Cardiovascular (e.g. arrhythmias and reduction in blood pressure) and haemorrhagic events (mostly associated with puncture sites) were reported most frequently. Cerebrovascular accidents occurred in 15/1598 patients (0.9%) treated with APSAC, of which 10 cases could possibly have been related to treatment. Allergic-type reactions (e.g. anaphylaxis, bronchoconstriction, skin rashes) occurred in 61/1152 patients (5%) after APSAC and may have resulted from previous exposure to streptococcal infection. APSAC induces systemic fibrinogenolysis and a 'lytic' state characterised by reductions in fibrinogen, plasminogen, Factors II, V and VIII and alpha 2-antiplasmin, and an increase in fibrin degradation products, which return to normal over a period of 2 days.(ABSTRACT TRUNCATED AT 400 WORDS)