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

Abstract

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 less than 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 less than 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 less than 0.01). By the end of a 3 week follow-up period, seven APSAC-treated patients and six heparin-treated 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.

Comparative Tolerability Profiles of Thrombolytic Agents

“…Inotropic therapy is occasionally required as well. The thrombolytic Bassand et al (1989Bassand et al ( , 1991; GISSI-1 (1986);Goldhaber et al (1988); Graor & Olin (1989); ISIS-2 (1988); Rao at al. (1988); Wilcox at al.…”

Review: The revised role of ACE-inhibition after myocardial infarction in the thrombolytic/primary PCI era

“…32 Both early and late reperfusion of the infarctrelated coronary artery have been shown to reduce the extent of LV dilatation. [3][4][5][6][7][8][33][34][35][36][37] The results of almost 14,000 mainly thrombolysed patients included in the echocardiographic substudy of Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico (GISSI-3) showed no relevant change in LV size after a median of 10 days following MI (Figure 1). Interestingly, even patients predicted to be at high risk of long-term LV dilatation showed only limited progression of LV dilatation after 10 days.…”

“…by administration of thrombolytic therapy or direct percutaneous coronary intervention [PCI]) proved effective in preventing or minimising LV dilatation and reducing cardiac morbidity and mortality by limiting the infarct size. [3][4][5][6][7][8] Secondly, angiotensin-converting enzyme (ACE) inhibitors attenuated LV dilatation and reduced cardiac morbidity and mortality, especially in patients with LV dysfunction and/or without thrombolytic therapy. [9][10][11][12] However, after early reperfusion, the extent of residual LV dilatation is often limited, and additional reduction of LV dilatation by ACE inhibitor (ACE-I) treatment may be negligible.…”

Coronary Thrombolysis in Women

“…A number of studies has been per formed evaluating the effect(s) of thrombo lytic therapy on left ventricular preservation in AMI (table 4). Despite a poorer prognosis in women following AMI which may result from poorer overall left ventricular function, gender analyses have not been performed in the large series [31, [46][47][48][49], Of interest and concern, the recently published TIMI-I an cillary study, which assessed quantitative re gional ventricular function after thrombo lytic therapy [50], reported a significantly greater percentage of women in whom a pre discharge radionuclide ventriculogram was not performed. It is clear that future studies must be designed and analyzed to detect potential gender differences in left ventricu lar function following thrombolytic therapy in AMI.…”