Multicenter reperfusion trial of intravenous anisoylated plasminogen streptokinase activator complex (APSAC) in acute myocardial infarction: controlled comparison with intracoronary streptokinase

The recent establishment of a firm therapeutic role for reperfusion in acute myocardial infarction has stimulated interest in the development of more ideal thrombolytic agents. Anisoylated plasminogen streptokinase activator complex (APSAC) is a new plasminogen activator possessing properties that are promising for intravenous thrombolytic application in acute myocardial infarction. To assess the reperfusion potential of intravenous APSAC, a multi-center, angiographically controlled reperfusion trial was performed. An approved thrombolytic regimen of intracoronary streptokinase served as a control. Consenting patients with clinical and electrocardiographic signs of acute myocardial infarction were studied angiographically and 240 qualifying patients with documented coronary occlusion (flow grade 0 or 1) were randomized to treatment in less than 6 h of symptom onset (mean 3.4 h, range 0.4 to 6.0) with either intravenous APSAC (30 U in 2 to 4 min) or intracoronary streptokinase (160,000 U over 60 min). Both groups also received heparin for greater than or equal to 24 h. Reperfusion was evaluated angiographically over 90 min and success was defined as advancement of grade 0 or 1 to grade 2 or 3 flow. Rates of reperfusion for the two treatment regimens were 51% (59 of 115) at 90 min after intravenous APSAC and 60% (67 of 111) after 60 min of intracoronary streptokinase (p less than or equal to 0.18). Reperfusion at any time within the 90 min was observed in 55 and 64%, respectively (p less than or equal to 0.16). Time to reperfusion occurred at 43 +/- 23 min after intravenous and 31 +/- 17 min after intracoronary therapy. The success of intravenous therapy was dependent on the time to treatment: 60% of APSAC patients treated within 4 h exhibited reperfusion compared with 33% of those treated after 4 h (p less than or equal to 0.01). Reperfusion rates were also dependent on initial flow grade (p less than or equal to 0.0001): 48% (81 of 168) for grade 0 (APSAC = 43%, streptokinase = 54%), but 78% for grade 1 (APSAC = 78%, streptokinase = 77%). APSAC given as a rapid injection was generally well tolerated, although the median change in blood pressure at 2 to 4 min was greater after APSAC than after streptokinase (-10 versus -5 mm Hg). Mean plasma fibrogen levels fell more at 90 min after the sixfold higher dose of APSAC than after streptokinase (to 32 versus 64% of control). Reported bleeding events were more frequent after APSAC but occurred primarily at the site of catheter insertion and no event was intracranial.(ABSTRACT TRUNCATED AT 400 WORDS)     

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.     

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 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.     

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 less than 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.     

Vasculitis complicating treatment with intravenous anisoylated plasminogen streptokinase activator complex in acute myocardial infarction

Vasculitis developed in six of 253 patients treated with intravenous anisoylated plasminogen streptokinase activator complex (APSAC) after acute myocardial infarction. All patients recovered spontaneously with no evidence of renal impairment and no long term sequelae. Although leucocytoclastic vasculitis and serum sickness have been reported after streptokinase treatment, such allergic reactions have not been described as a complication of other thrombolytic agents.     

Vasculitis complicating treatment with intravenous anisoylated plasminogen streptokinase activator complex in acute myocardial infarction.

Vasculitis developed in six of 253 patients treated with intravenous anisoylated plasminogen streptokinase activator complex (APSAC) after acute myocardial infarction. All patients recovered spontaneously with no evidence of renal impairment and no long term sequelae. Although leucocytoclastic vasculitis and serum sickness have been reported after streptokinase treatment, such allergic reactions have not been described as a complication of other thrombolytic agents.     

Effects of tissue-type plasminogen activator and anisoylated plasminogen streptokinase activator complex on mortality in acute myocardial infarction

An overview of eight randomized controlled trials of tissue-type plasminogen activator (Alteplase or Duteplase) and 10 of anisoylated plasminogen streptokinase activator complex (Anistreplase) showed that the odds of early death were reduced by 29% by tissue-type plasminogen activator and 46% by anisoylated plasminogen streptokinase activator complex, with overlapping 95% confidence intervals. Although the beneficial effects of both agents are consistent and are strengthened when all the trials are considered together, the available data do not permit comparisons of the relative efficacy of these two agents with each other or with streptokinase.     

A systemic non-lytic state and local thrombolytic failure of anistreplase (anisoylated plasminogen streptokinase activator complex, APSAC) in acute myocardial infarction

The relation between coronary thrombolysis and coagulation variables after administration of anistreplase (anisoylated plasminogen streptokinase activator complex, APSAC) was studied in patients with an acute myocardial infarction. Fifty eight consecutive patients with acute myocardial infarction were given 30 U of anistreplase intravenously within 4 hours of the onset of symptoms. A fall in the plasma concentration fibrinogen to less than 1.0 g/l 90 minutes after administration of anistreplase was considered to reflect a systemic lytic state. Coronary angiography was performed 48 hours after thrombolytic treatment. The overall patency rate was 74% (43/58). Patency rates were significantly different in patients with a systemic lytic (83% (43/52)) and a systemic non-lytic state (0% (0/6)). The absence of a systemic lytic state after anistreplase administration seemed to be highly predictive of the failure of coronary thrombolysis. Coagulation studies showed evidence of inhibition of anistreplase induced fibrinolytic activity which may explain the failure of thrombolytic treatment in patients with evidence of a systemic non-lytic state.     

A systemic non-lytic state and local thrombolytic failure of anistreplase (anisoylated plasminogen streptokinase activator complex, APSAC) in acute myocardial infarction.

The relation between coronary thrombolysis and coagulation variables after administration of anistreplase (anisoylated plasminogen streptokinase activator complex, APSAC) was studied in patients with an acute myocardial infarction. Fifty eight consecutive patients with acute myocardial infarction were given 30 U of anistreplase intravenously within 4 hours of the onset of symptoms. A fall in the plasma concentration fibrinogen to less than 1.0 g/l 90 minutes after administration of anistreplase was considered to reflect a systemic lytic state. Coronary angiography was performed 48 hours after thrombolytic treatment. The overall patency rate was 74% (43/58). Patency rates were significantly different in patients with a systemic lytic (83% (43/52)) and a systemic non-lytic state (0% (0/6)). The absence of a systemic lytic state after anistreplase administration seemed to be highly predictive of the failure of coronary thrombolysis. Coagulation studies showed evidence of inhibition of anistreplase induced fibrinolytic activity which may explain the failure of thrombolytic treatment in patients with evidence of a systemic non-lytic state.     

A european multicenter and randomized study of APSAC versus streptokinase in myocardial infarction

In a multicentre randomized open study conducted on two parallel groups the effectiveness of APSAC was compared with that of streptokinase (SK) in 116 cases of myocardial infarction treated during the first 2.75 hours. APSAC (30 IU) was administered by intravenous bolus injection over 2 to 5 minutes, and SK (1.5 million IU) by intravenous infusion over 60 minutes. The patency of the coronary artery responsible for myocardial infarction was evaluated by coronary arteriography performed 1.74 h on average after the beginning of treatment; it was 70 p. 100 in the APSAC group and 51 p. 100 in the SK group (p less than 0.05). The fall in plasma fibrinogen was similar in both groups (mean minimum level; 0.2 g/l). Haemorrhages occurred in 9/58 patients treated with APSAC (15.5 p. 100) and in 13/58 patients treated with SK (22.4 p. 100); these haemorrhages took place during the first 24 hours in 4 patients of the APSAC group and in 10 patients of the SK group. Five patients died: 2 in the APSAC group and 3 in the SK group. In a subgroup of 38 patients who underwent 3 control coronary arteriographies (at 90 min, 24 hours and 3 weeks), the patency rates were 63 p. 100, 82 p. 100 and 93 p. 100 respectively with APSAC and 44 p. 100, 86 p. 100 and 92 p. 100 respectively with SK (NS). No coronary reocclusion occurred in the APSAC group, as against 3 (1 early, 2 delayed) in the SK group. It is concluded that APSAC seems to be more effective than intravenous streptokinase; it is easier to administer (bolus injection) and does not carry a higher risk of haemorrhage.     

A randomized trial of intravenous heparin in conjunction with anistreplase (anisoylated plasminogen streptokinase activator complex) in acute myocardial infarction: The Duke University clinical cardiology study (DUCCS) 1

Objectives. We designed a randomized trial to evaluate the effects of heparin administration in conjunction with anistreplase (anisoyiated plasminogen streptekinase activator complex [APSAC]) on arterial patency and clinical end points.Background. The role of conjunctive intravenous heparin therapy with APSAC has not been tested despite the recommendations that intravenous heparin should be used.Methods. Four hours after APSAC administration, 250 patients with acute myocardial infarction were randomly assigned to receive 325 mg of either aspirin alone or aspirin and a continuous infusion of heparin (15 IU/kg body weight per h). Clinical ischemic events and bleeding complications were monitored On hospital day 5, coronary arteriography and left veetriculography were performed.Results. The primary end point of the trial (the combined outcome of death, reinfarction, recurrent ischemia and occlusion of the infarct-related artery) occurred in 42% of the heparin-treated group versus 43% of the group without heparin (p = 0.94). A patent infarct-related artery was present in 80% of the treated with heparin and in 73% of those treated without heparin (p = 0.26). Left ventricular function, as measured by ejection fraction, was well preserved in both groups (52% vs. 50.5%, respectively, p = 0.29). The overall bleeding rate was higher in patients with (32%) than without (17.2%) heparin (p = 0.006).Conclusions. Weight-adjusted intravenous heparin therapy after APSAC in acute myocardial infarction does not reduce the combined incidence of death, reinfarction, recurrent ischemia and ccclusion of the infarct-related artery. Furthermore, withholding intravenous heparin therapy is associated with a 46% reduction in bleeding complications. Our findings do not support the addition of intravenous heparin after APSAC therapy, as currently recommended, and suggest that a strategy of withholding heparin is simpler and safer and does not place the patient at increased risk for ischemic complications after myocardial infarction.     

Potential cost effectiveness of intravenous tissue plasminogen activator versus streptokinase for acute myocardial infarction.

OBJECTIVE: An economic evaluation of the potential incremental benefits of intravenous tissue plasminogen activator (tPA) versus streptokinase (SK) for treatment of acute myocardial infarction. DESIGN: Cost effectiveness analysis from a third-party payer perspective (Ontario Ministry of Health). ECONOMIC INPUTS: Fully allocated costs for cardiovascular procedures and hospitalization for myocardial infarction were obtained anonymously for four Ontario teaching hospitals and converted to 1988 Canadian dollars. Professional charges were taken from the provincial health insurance fee schedule and drug costs obtained from the manufacturers. CLINICAL INPUTS: The baseline analysis was for nonelderly patients with uncomplicated myocardial infarctions; sensitivity analyses allowed extrapolation to higher risk subgroups. Short and longer term mortality and short term invasive procedure rates were estimated using data from clinical trials. MAIN RESULTS: If tPA achieves a 1% short term mortality advantage over SK with no advantages for other survivors, cost per life-year gained can be comparable to other cardiovascular interventions at $58,600. In the absence of immediate survival advantages, but assuming greater left ventricular preservation, the constant annual hazard rate advantage must be about 0.5% per year for competitive cost effectiveness ratios. CONCLUSIONS: A full range of projections is presented to help guide the policy decisions that will arise in the wake of the Global Utilization of SK and tPA for Occluded Coronary Arteries (GUSTO) trial. The analysis also illustrates the general importance of considering longer term effects of in-hospital therapies for acute myocardial infarction.     

Prospective randomized trial of intravenous and intracoronary streptokinase in acute myocardial infarction

To evaluate the relative thrombolytic efficacy and complications of intracoronary vs high-dose, short-term intravenous streptokinase infusion in patients with acute myocardial infarction, we performed baseline coronary arteriography and then randomly allocated 51 patients with acute myocardial infarction to receive either intracoronary (n = 25) or intravenous (n = 26) streptokinase. Patients getting the drug by the intracoronary route received 240,000 IU of streptokinase into the infarct-related artery over 1 hr, whereas those getting the drug by the intravenous route received either 500,000 IU of streptokinase over 15 min (n = 10) or 1 million IU of streptokinase over 45 min (n = 16). Angiographically observed thrombolysis occurred in 76% (19/25) of the patients receiving intracoronary streptokinase, in 10% (1/10) of the patients receiving 500,000 IU of streptokinase intravenously, and in 44% (7/16) of the patients receiving 1 million IU of streptokinase intravenously. Among patients in whom thrombolysis was observed, mean elapsed time from onset of streptokinase infusion until lysis was 31 +/- 18 min in patients receiving intracoronary streptokinase and 38 +/- 20 min in those receiving intravenous streptokinase (p = NS). Among patients in whom intravenous streptokinase "failed," intracoronary streptokinase in combination with intracoronary guidewire manipulation recanalized only 7% (1/15). Fibrinogen levels within 6 hr after streptokinase were significantly lower in the patients receiving intravenous streptokinase (39 +/- 17 mg/dl) than the levels in those receiving intracoronary streptokinase (88 +/- 70 mg/dl) (p less than .05) but were similar 24 hr after streptokinase in the two groups. Bleeding requiring transfusion occurred in one patient in each group. Thus, in this prospective randomized trial of intracoronary vs intravenous streptokinase, hemorrhagic complications were few, although both regimens produced a systemic lytic state. Although the thrombolytic efficacy of intracoronary streptokinase was superior to that of high-dose, short-term intravenous streptokinase, the higher-dose intravenous regimen (1 million IU over 45 min) achieved thrombolysis in a significant minority (44%) of patients and might be useful therapy for patients not having access to emergency catheterization.     

Effects of early thrombolytic therapy (anistreplase versus streptokinase) on enzymatic and electrocardiographic infarct size in acute myocardial infarction. TEAM-2 Investigators

The effects of thrombolytic therapy on enzymatic and electrocardiographic indexes of myocardial infarction were examined in 370 patients who were enrolled within 4 hours of onset of symptoms and were randomized to blinded therapy with intravenous anistreplase (30 U/5 min, n = 188) or streptokinase (1.5 million IU/1 hour, n = 182). Creatine kinase and its MB isoenzyme were initially measured every 4 to 6 hours, and lactic dehydrogenase (LDH) and its cardiac isoenzyme (LDH-1) every 8 to 12 hours. Electrocardiograms were obtained before, and at 90 minutes and 8 hours after starting thrombolysis, and on discharge. Enzymatic and electrocardiographic measures of infarction were compared between drug treatment and patency groups. Early patency was associated with significant reductions in peak values for each of 4 cardiac enzymes (averaging 21 to 25%, p less than 0.01 to 0.001), even though later rescue procedures were often used in the nonpatient group; times to peaks were also reduced for 3 of the enzymes. Treatment with anistreplase was associated with enzymatic peaks that tended to be lower than with streptokinase (6 to 16%), approaching or reaching significance for LDH (p less than or equal to 0.07) and LDH-1 (p less than or equal to 0.04); times to peaks were similar. Early patency favorably affected electrocardiographic indexes. Summed ST-segment elevations resolved more rapidly (p less than or equal to 0.04), summed Q-wave amplitude was reduced by 32% (p less than or equal to 0.01), and total QRS infarct score on discharge was 22% less (p less than or equal to 0.006) in those achieving early patency. Small differences in electrocardiographic indexes between the 2 drug treatment groups were not significant. These results support use of early reperfusion to reduce infarct size in acute myocardial infarction with administration of streptokinase and anistreplase.     

An angiographic study of intracoronary streptokinase versus intravenous tissue plasminogen activator after failed coronary thrombolysis with intravenous streptokinase

Objective The medical treatment of failed intravenous streptokinase in patients with acute transmural myocardial infarction using angiographic endpoints.Design Prospective open angiographic comparison of intracoronary streptokinase with intravenous tissue plasminogen activator. Setting: Single center study in a tertiary institution.Subjects Eighty-five patients with acute myocardial infarction within 4 hours after symptom onset. Treatment regimens: The subjects received 1.5 million U intravenous streptokinase. Coronary angiography within 48 hours (median 19 hours) showed infarct-related vessel patency in 65 patients (76%). In the catheterization laboratory the 20 patients (24%) with failed intravenous streptokinase received repeat thrombolysis immediately after angiography. The first 10 patients with failed intravenous streptokinase received intracoronary streptokinase at a dose of 4000 U/min in the occluded infarctrelated artery for a maximum of 1 hour. The subsequent 10 patients received high-dose front-loaded intravenous tissue plasminogen activator (100 mg in 1 hour).Results In none of the patients receiving repeat streptokinase was reperfusion obtained. In 6 of 10 (60%) of the patients receiving tissue plasminogen activator, reperfusion was seen within 60 minutes (p < 0.005 vs. intracoronary streptokinase). One patient (5%) died and two refused follow-up angiography. Seventeen (88%) patients underwent angiography 3 months later according to the protocol. Two patients showed a persistently reperfused infarct-related artery, three reoccluded, four spontaneously reperfused, and eight had a persistently occluded infarct-related artery. The left ventricular ejection fraction was slightly higher at 3 months, and there were no differences between the patients with open vessels (increase + 7.7 ± 5.8%) and those with persistently occluded vessels (increase +5.8 ± 6.8%)Conclusions Repeat thrombolysis after failed intravenous streptokinase can be achieved with front-loaded intravenous tissue plasminogen activator but not with intracoronary streptokinase. Although patient numbers are small and repeat thrombolysis was performed rather late, this study leads the way to affordable optimization of thrombolysis, which needs large-scale testing.     

Randomized comparison of intravenous versus intracoronary streptokinase for myocardial infarction

The efficacy of intravenous (i.v.) thrombolytic therapy has not been firmly established in comparison with the intracoronary (i.c.) route of administration. In a randomized trial of 28 patients who underwent angiography before and during i.v. and i.c. administration of Streptokinase (STK), recanalization was achieved in 73% of patients who received the drug by the i.c. route, compared with 62% of patients who received the drug by the i.v. route (difference not significant). Reopening took 28 minutes for i.c. STK and 39 minutes for i.v. STK. Patients in whom recanalization was successful using either route of administration had shorter euglobulin lysis times and lower fibrinogen levels than did patients in whom it was not successful (p < 0.05). Bleeding complications were closely correlated with heparinization after thrombolysis rather than with STK itself. These results in a limited patient series suggest that early administration of i.v. STK in the emergency department may yield recanalization rates similar to those for the i.c. route and may benefit myocardial preservation by restoring flow much earlier.     

Comparative effects of APSAC and rt-PA on infarct size and left ventricular function in acute myocardial infarction. A multicenter randomized study

BACKGROUND. Recombinant tissue-type plasminogen activator (rt-PA or alteplase) and anisoylated plasminogen streptokinase activator complex (APSAC or anistreplase) have been demonstrated to limit infarct size significantly and to preserve left ventricular function when injected soon after acute myocardial infarction. However, as yet, the efficacy and safety of these two thrombolytic agents have not been directly compared in one trial; this was the aim of this study. METHODS AND RESULTS. One hundred eighty-three patients suffering from a first acute myocardial infarction were randomly allocated to either APSAC (30 units over 5 minutes) or single-chain rt-PA (100 mg over a 3-hour period) within 4 hours of the onset of symptoms. Global and regional left ventricular function were assessed from contrast angiography an average of 5.3 +/- 2.3 days after initial therapy. Radionuclide angiography and thallium-201 single-photon emission computerized tomography were performed before hospital discharge. Infarct size was assessed by single-photon emission computerized tomography and expressed in percentage of the total myocardial volume. Ninety patients received APSAC and 93 received rt-PA within a mean period of 172 +/- 52 minutes after the onset of symptoms. The two groups were similar in age, location of the acute myocardial infarction, Killip class, and time of randomization. The patency rate of the infarct-related artery was 72% in the APSAC group and 76% in the rt-PA group (NS). Initial and predischarge left ventricular ejection fraction as well as infarct size were similar in both therapeutic groups (0.50 +/- 0.14 versus 0.52 +/- 0.12 for initial and 0.48 +/- 0.10 versus 0.47 +/- 0.10 for predischarge ejection fraction, 11 +/- 7% versus 9 +/- 7% for infarct size, respectively, for APSAC- and rt-PA-treated patients). Bleeding complications requiring blood transfusion occurred in one APSAC patient and in two rt-PA patients. One patient in the rt-PA group died of a massive intracranial hemorrhage. At the end of the 3-week follow-up period, five APSAC patients (5.5%) and seven rt-PA patients (7.5%) had died. CONCLUSIONS. The early infusion of APSAC or rt-PA in acute myocardial infarction produced a similar patency rate, limitation of infarct size, and preservation of left ventricular systolic function with an equivalent rate of bleeding complications.     

Thrombolysis in acute myocardial infarction: effect of intravenous followed by intracoronary streptokinase application on estimates of infarct size

The effect of pretreatment with intravenous infusion of streptokinase (SK) (16,700 U/min for 90 minutes), started after diagnosis and followed by intracoronary application (2000 U/min) (protocol 1), was assessed retrospectively in 55 consecutive patients with acute transmural myocardial infarction (MI). Another 46 patients with acute MI treated previously by intracoronary thrombolysis served as control subjects (protocol 2). Reperfusion at first coronary injection was observed after pretreatment in 25 patients (45%), but in no control patient (p less than 0.001). Fifteen patients with successful pretreatment (group A), 20 patients with successful treatment according to protocol 2 (group B) and 9 patients with unsuccessful thrombolysis (group C) were restudied after 4 weeks. Data from patients with reinfarction, coronary bypass surgery or percutaneous transluminal coronary angioplasty before restudy were excluded. Thallium-201 scintigraphy was performed before and 24 hours after treatment, serum creatine kinase activity was measured every 8 hours for 3 days and regional ejection fraction (EF) of acute MI was determined before and 4 weeks after treatment. The scintigraphic, enzymatic and hemodynamic data before treatment indicated severe and comparable ischemia among the 3 groups. The thallium-201 perfusion defect decreased in group A (from 41 to 21%, p less than 0.01) and in group B (from 38 to 26%, p less than 0.01), but did not change in group C (from 37 to 31%, difference not significant). Peak serum creatine kinase levels normalized by the perfusion area of acute MI was 20, 33 and 58 U/liter unit in groups A, B and C. The mean values of groups A and C were significantly different (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)