Streptokinase Group Research Articles

Effect of Intravenous Streptokinase as Compared with That of Tissue Plasminogen Activator on Left Ventricular Function after First Myocardial Infarction

In a double-blind trial comparing two thrombolytic agents as treatment for acute myocardial infarction, we randomized 270 consecutive patients an average (+/- SD) of 2.5 +/- 0.6 hours after the onset of chest pain from a first myocardial infarction--135 to receive intravenous streptokinase (1.5 million units over 30 minutes) and 135 to receive intravenous recombinant tissue plasminogen activator (rt-PA) (100 mg over three hours). The primary end point was left ventricular function as assessed by cineangiography performed three weeks after infarction. The effects of the two agents on left ventricular function were similar. The ejection fraction was identical (58 +/- 12 percent) in both groups. The end-systolic volume was 61 +/- 29 ml in the streptokinase group and 66 +/- 31 ml in the rt-PA group (P not significant). Patency rates at three weeks for the infarct-related artery were also similar (75 percent in the streptokinase group and 76 percent in the rt-PA group). Reinfarction rates at 30 days were the same (5 percent) in both groups. One patient had a fatal intracerebral hemorrhage 13 hours after receiving rt-PA, and another had a fatal cerebellar hemorrhage 21 hours after receiving rt-PA for reinfarction nine days after treatment with streptokinase. An intention-to-treat analysis revealed that mortality at 30 days was 3.7 percent in the rt-PA group as compared with 7.4 percent in the streptokinase group (P greater than 0.2). Follow-up for a mean of 9.0 months revealed no significant difference in survival; we observed 12 deaths (8.9 percent) in the streptokinase group and 8 deaths (5.9 percent) in the rt-PA group (P = 0.34). We conclude that rt-PA and streptokinase, in the doses given, have similar effects on left ventricular function after a first myocardial infarction. Because of the small number of deaths, it is not possible to determine whether their effects on mortality are similar.

Plasminogen activator italian multicenter study (PAIMS): Comparison of intravenous recombinant single-chain human tissue-type plasminogen activator (rt-pa) with intravenous streptokinase in acute myocardial infarction

A single chain preparation of recombinant tissue-type plasminogen activator (rt-PA) was compared with intravenous streptokinase to determine coronary thrombolytic efficacy in patients with acute myocardial infarction <3 h old. Eighty-six patients were randomly selected to receive the intravenous cumulative dose of 100 mg rt-PA and 85 patients to receive 1.5 million units streptokinase. At 240 min after initiation of the thrombolytic therapy noninvasive signs of sustained reperfusion occurred in 79% of patients in both groups (p = NS). Patency of the infarct-related vessel at follow-up angiography was observed in 81% of patients in the rt-PA group and 74% of patients in the streptokinase group (p = NS). At hospital discharge, compared with admission, echocardiographically determined left ventricular ejection fraction increased from 52 ± 11 % to 56 ± 10% (p < 0.01) in the rt-PA group; changes in the streptokinase group (50 ± 9% to 51 ± 11%) were not significant.A nadir value of <1 g/liter fibrinogen plasma level occurred in 6 patients (7%) receiving rt-PA versus 74 patients (87%) receiving streptokinase (p < 0.0001). Plasma levels of fibrin(ogen) degradation products were more than doubled in the streptokinase group (p < 0.01). One patient in the streptokinase group developed a fatal intracranial hemorrhage; five others showed a decline in hemoglobin ⩾5 g/dl. Other clinical events in the streptokinase-treated group included allergic reactions (four patients) and intrahospital reinfarction (two patients). None of these events occurred in the rt-PA group. This rt-PA preparation achieves a high rate of stable coronary reperfusion, comparable with that of intravenous streptokinase and is associated with fewer complications and a significant sparing of the hemostatic system.

Nuclear magnetic resonance and radionuclide angiographic assessment of acute myocardial infarction in a randomized trial of intravenous streptokinase

Sixty-six patients presenting with their first evolving transmural acute myocardial infarction (AMI) were randomized to receive either streptokinase (n = 41) or placebo therapies (n = 25) within 6 hours of the onset of chest pain. These patients then underwent supine rest, exercise and after-nitroglycerin radionuclide angiography 3 weeks after AMI. Nuclear magnetic resonance (NMR) imaging was performed at 3 weeks as a more direct estimate of AMI size. Although peak creatine kinase values were comparably elevated between groups (2,367 ± 1,486 IU/liter for streptokinase vs 2,637 ± 1,305 IU/liter for placebo), there was a significant reduction in NMR-measured AMI size in the streptokinase group (3 ± 2% of left ventricular volume vs 10 ± 4% in the placebo group, p < 0.05). This occurred despite comparable resting (54 ± 11 vs 47 ± 10% and exercise (53 ± 12 vs 49 ± 11%) global ejection fractions. However, following nitroglycerin, there was an improvement in global ejection fraction in the streptokinase-treated group that was not observed with placebo (61 ± 13 vs 48 ± 10%, p < 0.05). A similar pattern was also observed with regional functional analysis. Thus, streptokinase therapy leads to a significant reduction in NMR-measured AMI size and to a greater degree of reversible left ventricular dysfunction.

Effects of thrombolytic therapy in unstable angina: Clinical and angiographic results

The incidence of intracoronary thrombus and the effects of thrombolytic therapy were studied in 41 patients with unstable angina. All patients underwent coronary angiography 2 to 69 h (mean 19) after their last attack of chest pain. Immediately after angiography, 21 patients received intracoronary streptokinase (250,000 IU in 45 min) and were retrospectively analyzed. Twenty patients received intravenous recombinant tissue-type plasminogen activator (rt-PA) (100 mg in 3 h) and were involved in a prospective study.Eleven of the 21 patients from the streptokinase group and 11 of the 20 patients from the rt-PA group showed a decrease in the severity of the coronary stenosis on repeat angiography 1 day later. A decrease in coronary obstruction was primarily observed in 10 of 13 patient; with a complete stenosis and in 6 of 9 patients with a subtotal stenosis and markedly diminished coronary flow. Improvement in coronary anatomy was not determined by the clinical characteristics of the patients. Twenty-eight of the 41 patients had angiographic evidence of intracoronary thrombus formation before and 16 had such evidence after thrombolytic treatment. Nine patients developed a small increase in serum cardiac enzymes before or during treatment. Ischemic symptoms and the incidence of surgical or angioplastic intervention were not different in patients with or without a reduction in coronary artery stenosis after fibrinolytic therapy.These observations suggest a high incidence of coronary thrombosis in patients with unstable angina. The data do not permit assessment of the clinical therapeutic efficacy of thrombolylic therapy. Better risk stratification and placebo-controlled prospective studies are required to obtain information on the risk/benefit ratio of such therapy in unstable angina.

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.

The Safety of Combined Thrombolysis and â-Adrenergic Blockade in Patients with Acute Myocardial Infarction: A Randomized Study

To assess the safety of combined intervention in acute myocardial infarction, a pilot study of thrombolysis and beta-adrenergic blockade was performed. Twenty-five subjects were randomized to therapy with intravenous (IV) metoprolol and IV streptokinase (group 1) or to IV metoprolol (group 2) alone. Two-dimensional echocardiography was performed before intervention and five days later. The mean time from onset of symptoms to intervention was 1.92 hours. No major adverse reactions related to the intervention were observed in either group. Significant improvement from baseline was observed with combined therapy on both the biplane mean ejection fraction (p less than .02) and a calculated wall motion index of regional wall motion abnormalities (p less than .002). The presumed reperfusion rate was significantly higher in group 1 (p less than .03). Intravenous metoprolol and IV streptokinase in combination was found to be safe in the acute phase of acute myocardial infarction when administered to appropriate patients without contra-indications and deserves further study.

Thrombolysis in myocardial infarction (TIMI) trial—Phase I: Hemorrhagic manifestations and changes in plasma fibrinogen and the fibrinolytic system in patients treated with recombinant tissue plasminogen activator and streptokinase

Two hundred ninety patients with acute myocardial infarction were treated according to random assignment with an intravenous infusion of either 80 mg of recombinant tissue plasminogen activator (rt-PA) over 3 h or 1.5 million units of Streptokinase over 1 h. Patients received an intravenous bolus of heparin (5,000 U [USP]) before pretreatment coronary angiography and a continuous infusion (1,000 U/h) starting 3 h later. The frequency of major and minor hemorrhagic events (33% rt-PA, 31% Streptokinase) and associated transfusions (22% rt-PA, 20% streptokinase) were comparable in both groups. More than 70% of bleeding episodes in each group occurred at catheterization or vascular puncture sites.Precipitable fibrinogen levels, measured in plasma samples collected in the presence of a protease inhibitor (aprotinin), declined in rt-PA and streptokinase groups by averages of 26 and 57% at 3 h and by 33 and 58% at 5 h, respectively (rt-PA versus streptokinase, p < 0.001). At 5 h the plasma plasminogen declined by 57% (rt-PA) and 82% (streptokinase) (p < 0.001); plasma fibrin(ogen) degradation products were higher in streptokinase-treated patients (244 ± 12 μg/ml, mean ± SE) than in rt-PA-treated patients (97 ± 9 μg/ml, p < 0.001). At 27 h, plasma fibrinogen and plasminogen levels were lower and fibrin(ogen) degradation products higher than pretreatment levels in both groups. The frequency of hemorrhagic events was higher in patients with greater changes in plasma factors at 5 h; within treatment groups the levels of fibrin(ogen) degradation products correlated with bleeding complications (p < 0.005).Thus, in the doses administered, rt-PA induces systemic fibrinogenolysis that is substantially less intense than that induced by streptokinase. The high frequency of bleeding encountered is retated to the protocol used, including vigorous anticoagulation, arterial punctures and thrombolytic therapy. These findings emphasize the need for avoidance of invasive procedures and for meticulous care in the selection and management of patients subjected to thrombolytic therapy.

Systemic effects of thrombolytic drugs in acute myocardial infarction: Comparison of intravenous APSAC (BRL 26921) and intracoronary streptokinase

The systemic effects of intravenous anisoylated plasminogen-streptokinase activator complex (APSAC; BRL 26921; 30 U) and Intracoronary streptokinase (250 000 U) were compared in 70 patients with acute myocardial infarction. In 5 patients no signs of a systemic lytic state were observed. In all other patients, significant consumption of coagulation and fibrinolytic factors occurred: fibrinogen levels decreased by 85% in the APSAC group and 78% in the streptokinase-treated patients. For plasminogen the decreases were 68% and 64% and for α 2-antiplasmin activity > 95% and 87% (APSAC and streptokinase, respectively). Fibrin(ogen) degradation products were generated to mean levels of 739 mg/L and 355 mg/L, respectively. Although there was a trend for the lytic state to be more profound in the APSAC-treated patients, no difference with the streptokinase group was observed with regard to bleeding complications or therapeutic efficacy, which was 64% and 68% respectively for APSAC and streptokinase. The total fibrinolytic activity, measured as euglobulin clot lysis time, sustained longer in the APSAC group, which might be the reason for the low reocclusion rate (4.5%)) in comparison with the SK group (13%).

LONG-TERM EFFECTS OF INTRAVENOUS THROMBOLYSIS IN ACUTE MYOCARDIAL INFARCTION: FINAL REPORT OF THE GISSI STUDY

Long-term follow-up of 98·3% of the 11 712 patients recruited in the GISSI trial of intravenous streptokinase (SK) in acute myocardial infarction has shown persistence of the beneficial effect observed during the hospital phase. At 12 months a significant difference in mortality was seen in the whole population (17·2% in SK group versus 19·0% in controls, p = 0·008, relative risk 0·90), and in the 0-3 and 3-6 h groups (relative risks 0·89 and 0·87, respectively). For most of the other strata according to which the trial population has been analysed, the magnitude and the direction of the effects were also substantially the same as those recorded in the hospital phase. SK thrombolysis should be considered among the recommended treatments of the acute phase, at least up to 6 h from onset of myocardial infarction.

Effects of early high-dose streptokinase intravenously on left ventricular function in acute myocardial infarction

One hundred seven patients who recently had acute myocardial infarction were randomly assigned either to standard heparin therapy or to intravenous streptokinase within 5 hours after the onset of symptoms in 7 hospitals without catheterization facilities. In the third week, the patients were referred to a university hospital, where the patency rate of the infarctrelated artery was studied by selective coronary arteriography and left ventricular function by radionuclide angiography. Fifty-five patients received heparin and 52 streptokinase within a mean period of 190 minutes after the onset of symptoms. Seven patients in the heparin group and 4 in the streptokinase group died in hospital. The patency rate of the infarct-related artery was identical in both groups (69% in the heparin group vs 68% in the streptokinase group). Left ventricular ejection fraction was not statistically different (0.44 ± 0.13 in the heparin group vs 0.45 ± 0.12 in the streptokinase group). Left ventricular ejection fraction was significantly higher in patients with a patent infarct-related artery than in patients with an obstructed infarct-related artery (0.49 ± 0.12 vs 0.41 ± 0.15, p < 0.01). In patients with inferior wall infarction, left ventricular ejection fraction was identical (0.50 ± 0.10 in the heparin group vs 0.52 ± 0.09, in the streptokinase group). In patients with anterior wall infarction, left ventricular ejection fraction was significantly higher in the streptokinase group than in heparin group (0.40 ± 0.10 vs 0.33 ± 0.09, p < 0.05). Analysis of regional wall motion revealed that improvement occurred in the lateral wall of the left ventricle. After a mean follow-up of 23 months, 3 patients in the heparin group and 1 patient in the streptokinase group died, yielding the mortality rate at the end of the follow-up period to 18.1 % in the heparin group on 9.6% in the streptokinase group. Thus, early intravenous administration of streptokinase may lead to significant preservation of left ventricular function in patients with anterior wall infarction. One may question the suitability and utility of intravenous thrombolysis in inferior wall infarction.

Factors affecting outcome of coronary reperfusion with intracoronary streptokinase in acute myocardial infarction

Aggressive interventionai therapy in acute myocardial infarction (AN) is expensive, time-consuming and not without significant risk. To determine which patients are most likely to benefit from such therapy, the effects of patient age, reperfusion success, admission left ventricular (LV) function, infarct location, admission clinical class, time from onset of pain to reperfusion and admission electrocardiographic findings on the outcome of coronary reperfusion in AMI were assessed in 292 prospectively studied, sequential patients from August 1980 to January 1984. Two hundred ten patients received intracoronary streptokinase (SK) therapy on admission and 82 patients, who either refused the protocol or met exclusion criteria, served as control subjests. Patients older than 65 years showed little improvement in 1-year mortality risk and no significant improvement in LV function during hospitalization after treatment with intracoronary SK. The remaining patients, 178 treated with SK and 48 control, were well matched and served as the basis for further comparisons. In. this subgroup of patients, reperfusion success was associated with improved survival and LV function (mortality rate 3%, vs 17% in control subjects; increase in ejection fraction [EF] 18% vs 4%). Patients with an EF of less than 45% on admission showed a 21 ± 30% increase in EF, compared with an increase in control subjects of 8 ± 19%, and a lower 1-year mortality rate than controls (6% vs 21%, p = 0.01). Patients with anterior AN had a significant increase in EF in the SK group (22 ± 31 %) and lower mortality compared with control subjects (5% vs 25%, p = 0.003). Patients admitted in Killip class I or II showed improvement after thrombolytic therapy in both LV function (14 ± 27% vs 4 ± 18%, p = 0.01) and mortality (3% vs 11%, p = 0.005). There was no correlation between duration of chest pain before reperfusion and change in LV function or 1-year mortality rate, although few patients were successfully reperfused less than 3 hours after onset of pain. Patients with inferior AN, an LVEF of more than 45% or who were older than 65 years showed no significant improvement in LV function or mortality after SK therapy. 0 waves occurring early in the course of AMI were not associated with increased mortality or poor ventricular function.

Analysis of reported randomized trials of streptokinase therapy for acute myocardial infarction in the 1980s

Trials of intracoronary (IC) and intravenous (IV) streptokinase (SK) therapy for myocardial infarction have shown variable effects on mortality and left ventricular (LV) function. A pooled analysis of 10 randomized trials involving a total of 14,355 patients was performed to look for overall trends in the change in mortality within 6 weeks (group A) and after 6 weeks (group B) of follow-up, and the change in LV function. All 10 trials, 7 with IC and 3 with IV SK, were randomized after 1980. There was a significant reduction in mortality risk in patients in group A treated with IV SK (pooled odds ratio = 0.81, 95% confidence interval = 0.73 to 0.90, p <0.001). In contrast, no significant differences in mortality were detected in patients in group B treated with IV SK or In patients in either group treated with IC SK. Two IV SK trials that prospectively stratified patient population according to duration of symptoms showed a greater reduction in mortality with administration of SK therapy within 3 hours of onset of symptoms. Analysis of LV function was performed before, within 96 hours after and 1 to 4 weeks after SK therapy. Only 2 of 7 IC SK trials showed significantly greater improvement in global LV ejection fraction in SK group compared with a control group, both showing improvement in LV function between early and late after treatment. Thus, IV SK therapy significantly reduces short-term risk of death after acute myocardial infarction; 2 trials show a greater reduction in mortality risk with earlier institution of IV SK therapy.

Reperfusion with streptokinase of an occluded right coronary artery: Effects on early and late right and left ventricular ejection fraction

The effect of coronary artery recanalization on early and late right and left ventricular function was studied in patients with an acute inferior wall myocardial infarction caused by an occlusion of the right coronary artery. Fifty-four out of 138 patients, with chest pain lasting less than 4 hours, with ST elevations diagnostic for acute myocardial infarction not responding to medical treatment, and without contraindication for thrombolytic therapy, had an occluded right coronary artery. In 26 of these 54 patients, the occlusion was located proximal to the first right ventricular branch. Fourteen of them were treated conventionally (group A) and 12 with intracoronary streptokinase (group B). In 28 patients, the occlusion was distal to the first right ventricular branch. Fifteen were treated conventionally (group C) and 13 with intracoronary streptokinase (group D). In all patients, coronary angiograms were made 2 to 3 weeks after acute myocardial infarction. A nuclear angiogram was made the second day after admission and 3 months later to determine right and left ventricular ejection fraction. Values of radionuclide left and right ventricular ejection fraction (RVEF) between acute study (< 48 hours after acute myocardial infarction [AMI] and late study (3 months after AMI) showed no significant improvement in the four groups of patients studied. Group A patients (patients with total occlusion of the right coronary artery treated conventionally) had a significantly lower RVEF acutely and at late study as compared to the other three groups. We conclude that patients with a proximally occluded right coronary artery treated with intracoronary streptokinase had a significantly better RVEF acutely and at 3 months follow-up compared to a conventionally treated group. There was no difference in the left ventricular ejection fraction between the groups.

A prospective placebo-controlled double-blind multicenter trial of intravenous streptokinase in acute myocardial infarction (ISAM): Long-term mortality and morbidity

Long-term mortality and morbidity of 1,741 patients with acute myocardial infarction, treated with intravenous streptokinase (1.5 million IU/h) or placebo, was assessed in a double-blind placebo-controlled trial (ISAM). At the 7 month follow-up, 94 (10.9%) of the 859 patients in the streptokinase group and 98 (11.1%) of the 882 patients in the placebo group had died; at an average follow-up of 21 months, 14.4% of the streptokinase group and 16.1% of the placebo group had died. The differences were not statistically significant. Long-term mortality was slightly higher in patients with anterior myocardial infarction and streptokinase treatment (20.1 versus 18.4%) and lower in patients with inferior myocardial infarction (10.2 versus 14.2%). Patients with previous myocardial infarction had a higher long-term mortality rate with streptokinase (34.9 versus 21.5% with placebo, p = 0.03). At 7 months, there were significantly more cases of reinfarction in the streptokinase group (7.2 versus 4.5%, p = 0.02). It is concluded that despite a significant limitation of infarct size by intravenous streptokinase, long-term mortality is only slightly reduced and reinfarction is significantly more frequent. Both findings suggest the need for complementary therapy such as revascularization procedures after thrombolysis.

Effects of early intracoronary streptokinase on infarct size estimated from cumulative enzyme release and on enzyme release rate: A randomized trial of 533 patients with acute myocardial infarction

The effects of early intracoronary streptokinase (SK) on enzymatic infarct size and rate of enzyme release were studied in a randomized multicenter trial. A total of 533 patients with acute myocardial infarction (AMI) were allocated to either the SK treatment group (n = 269) or the conventional (control) treatment group (n = 264). Enzymatic infarct size was represented by the cumulative quantity of α-hydroxybutyrate dehydrogenase (HBDH) released by the heart per liter of plasma in the first 72 hours. Rate of enzyme release was represented by the ratio of HBDH quantities released in 24 hours and 72 hours. On an “intention to treat” basis, the SK group had a smaller (by 30%; p = 0.0001) median enzymatic infarct size and a higher (by 35%; p = 0.0001) median rate of enzyme release than the control group. Limitation of infarct size was less apparent in patients treated with intracoronary SK only (25%) than in patients treated with intravenous plus intracoronary SK (34%). Compared to the control group, the enzyme release rate in patients treated with intracoronary SK only was slightly less (34%) than that in patients treated with intravenous plus intracoronary SK (38%). Patients with a patent infarct-related coronary artery at acute angiography had a median infarct size which was 55% ( p = 0.0001) smaller than the median infarct size of the control group, and the median rate of enzyme release was 38% ( p = 0.001) higher than the median release rate of the control group. Patients with successful recanalization during intracoronary SK infusion had a median infarct size which was 31% ( p = 0.002) smaller than the median infarct size of the control group and a median rate of enzyme release which was 42% ( p = 0.0001) higher than the median release rate of the control group. Patients with persistent coronary occlusion in spite of thrombolytic therapy had a median infarct size which was 11% (NS) higher than the median infarct size of the control group, although the median rate of enzyme release was still 23% ( p = 0.02) higher than the median release rate of the control group. It is concluded that thrombolysis in the early phase of AMI limits infarct size and that intracoronary SK treatment ltself accelerates the process of enzyme release from infarcted myocardium, independent of the angiographic result.

Prevention of subsequent exercise-induced periinfarct ischemia by emergency coronary angioplasty in acute myocardial infarction: Comparison with intracoronary streptokinase

To compare the efficacy of emergency percutaneous transluminal coronary angioplasty and intracoronary streptokinase in preventing exercise-induced periinfarct ischemia, 28 patients presenting within 12 hours of the onset of symptoms of acute myocardial infarction were prospectively randomized. Of these, 14 patients were treated with emergency angioplasty and 14 patients received intracoronary streptokinase. Recatheterization and submaximal exercise thallium-201 single photon emission computed tomography were performed before hospital discharge. Periinfarct ischemia was defined as a reversible thallium defect adjacent to a fixed defect assessed qualitatively. Successful reperfusion was achieved in 86% of patients treated with emergency angioplasty and 86% of patients treated with intracoronary streptokinase (p = NS). Residual stenosis of the infarct-related coronary artery shown at predischarge angiography was 43.8 +/- 31.4% for the angioplasty group and 75.0 +/- 15.6% for the streptokinase group (p less than 0.05). Of the angioplasty group, 9% developed exercise-induced periinfarct ischemia compared with 60% of the streptokinase group (p less than 0.05). Thus, patients with acute myocardial infarction treated with emergency angioplasty had significantly less severe residual coronary stenosis and exercise-induced periinfarct ischemia than did those treated with intracoronary streptokinase. These results suggest further application of coronary angioplasty in the management of acute myocardial infarction.

Treatment of Pulmonary Embolism with Full-dose Heparin, Streptokinase or Embolectomy - Results and Indications

The results of treatment of pulmonary embolism with heparin (n = 34), streptokinase (n = 28) or embolectomy (n = 25) are presented. The treatment groups represented different degrees of embolization with acute embolic scores (possible maximum: 20, mean +/- SD): 5 +/- 4, 9 +/- 3 and 13 +/- 3, respectively (p less than 0.0001). The post-treatment embolic score (mean +/- SD) for patients with acute massive central emboli (score greater than or equal to 9) was: 6 +/- 4 (n = 7) and 3 +/- 2 (n = 15) in the streptokinase and embolectomy groups, respectively, (p less than 0.01). The hospital mortality was 6% (n = 2), 21% (n = 6) and 20% (n = 5) in the heparin, streptokinase and embolectomy groups, respectively (p less than 0.05). The 5-year cumulative survival (+/- SE) was 68% +/- 10, 64% +/- 10 and 80% +/- 8, respectively (p: NS). The relative survival (hospital and late deaths, observed/expected) stratified according to acute embolic score showed the best results in the embolectomy group. Systolic pulmonary artery pressure greater than 60 mmHg was found in cases with a duration of symptoms greater than 7 days and/or with greater than or equal to 25 anamnestic recurrent embolic episodes before diagnosis, indicative of a gradual increase in pulmonary artery pressure and of partly organized non-lyseable emboli. Embolectomy carried a low risk of complications (8% with cerebral reduction). Streptokinase treatment was associated with serious complications (18% with cerebral reduction/fatal hemorrhage). Pulmonary embolectomy should be recommended in all cases with emboli in the main branches of the pulmonary artery.(ABSTRACT TRUNCATED AT 250 WORDS)

Randomized double-blind trial of intravenous streptokinase for acute myocardial infarction

To determine the efficacy of intravenously administered streptokinase (SK) on infarct artery patency, global left ventricular (LV) function and clinical course in transmural acute myocardial infarction (AMI), 38 patients were studied using a randomized, double-blind, placebo-controlled scheme. Nineteen patients received 1.0 million units of SK followed by 72 hours of heparin infusion and 19 received placebo followed by heparin infusion, all within 5 hours (mean 3.3 hours) after AMI onset. Patients ineligible for inclusion in the randomized trial were followed as a second, “historical control” group. Compared with placebo, SK caused a higher frequency of enzymatic evidence of reperfusion (6% vs 79%, p < 0.001) and of patent infarct-related arteries at predischarge coronary arteriography (64% vs 88%, difference not significant). (Patients in the control group had a relatively low frequency of spontaneous thrombolysis—28%.) In the SK group LV ejection fraction increased from early (average 7.3 hours after AMI) to late (predischarge) study (from 40% early to 47% late, p < 0.05); in the placebo group LV ejection fraction did not change significantly (from 41% to 42%). Predischarge exercise radionuclide ventriculography showed mild and similar degrees of inducible ischemia in both groups. After a mean of 12.8 months of follow-up, 1 SK patient and 4 placebo patients had died (difference not significant). In conclusion, intravenous SK is efficacious for thrombolysis in patients with AMI. It improves global LV function without augmenting exercise-inducible ischemia.

A randomized controlled trial of intravenous streptokinase in evolving acute myocardial infarction

To determine the efficacy of intravenous streptokinase in acute myocardial infarction, 52 patients were randomized to intravenous streptokinase or control groups. Time from onset of infarction to randomization was similar in the streptokinase group and control group, 4.9 ± 2.1 hours vs 5.4 ± 2.4 hours, respectively. The 28 streptokinase patients received an intravenous infusion of 700,000 units of streptokinase followed by full-dose anticoagulation. The 24 control patients received normal saline solution followed by full-dose anticoagulation. Of 28 streptokinase patients, 12 (43%) had noninvasive evidence of reperfusion by early peaking of serum creatine kinase (peak creatine kinase less than 16 hours after onset of infarction) vs 3 of 24 control patients (13%), p < 0.02. Two streptokinase patients (7%) had reperfusion arrhythmias during streptokinase infusion. One streptokinase patient (4%) and two control patients (8%) died during hospitalization. At angiography (16 ± 5 days after infarction) 22 of 26 streptokinase patients (85%) had a patent infarct-related coronary artery compared to 8 of 20 control patients (40%), p < 0.01. Comparison of radionuclide left ventricular ejection fraction assessed acutely (28 ± 10 hours after infarction) with left ventricular ejection fraction at hospital discharge (15 ± 3 days after infarction) showed no significant improvement in either the streptokinase or control group, 0% and +1%, respectively. At follow-up 13 ± 7 months after infarction, total mortality rate was similar in the streptokinase group and control group, 17.8% (5 of 28 streptokinase patients) and 20.8% (5 of 24 control patients), respectively. These results indicate that the incidence of a patent infarct-related coronary artery 2 to 3 weeks after acute myocardial inf arction was significantly greater in patients who received intravenous streptokinase compared to control patients.

Effects of early reperfusion in acute myocardial infarction on arrhythmias induced by programmed stimulation: A prospective, randomized study

This study compares inducibility of ventricular tachyarrhythmias by programmed electrical stimulation of the heart in patients with myocardial infarction with and without reperfusion after streptokinase therapy. Sixty-two consecutive patients admitted with an acute myocardial infarction were randomized to either combined intravenous and intracoronary streptokinase (streptokinase group) or to standard coronary care unit treatment (control group). Thirty-six of the 62 patients (21 patients from the streptokinase and 15 from the control group) with a first myocardial infarction were studied by programmed ventricular stimulation after a mean of 26 +/- 14 days. No patient had a history of antiarrhythmic drug use or documentation of a ventricular arrhythmia before the initial admission. A sustained ventricular arrhythmia was induced in 10 (48%) of the 21 patients randomized to streptokinase therapy and in all 15 (100%) control patients (p less than 0.001). Sustained monomorphic ventricular tachycardia was induced in 6 (29%) and 10 (67%) patients, respectively (p less than 0.05). To terminate an induced arrhythmia, direct current countershock was required in 33% of patients in the streptokinase group and 73% of patients in the control group (p less than 0.02). Seventeen of the 21 patients treated with streptokinase and no control patient had evidence of early reperfusion 200 +/- 70 minutes after the onset of pain. In comparison with patients without early reperfusion, patients in the reperfused group had a lower maximal serum creatine kinase value (p less than 0.01), a shorter time to peak creatine kinase value (p less than 0.001) and a higher angiographic left ventricular ejection fraction (62 versus 45%, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)