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PubMed1984

Intraarterial streptokinase infusion for acute popliteal and tibial artery occlusion.

Eight consecutive patients with acute thrombotic or embolic occlusion of the popliteal or tibial artery were treated with low-dose intraarterial streptokinase followed by arterial reconstructive surgery where appropriate. Three patients had acute thrombosis of a popliteal aneurysm with limb-threatening ischemia. All three were relieved of their acute ischemia by streptokinase infusion accompanied by lysis of clots in the popliteal artery outflow tract. Each patient then underwent elective popliteal aneurysm bypass. Four patients had acute embolic popliteal or tibial artery occlusion. Each was relieved of ischemic symptoms. One required surgery to remove residual clot. One patient with thrombosis of the tibioperoneal trunk did not have a decrease in symptoms with streptokinase infusion, but did experience sufficient outflow tract thrombolysis to permit construction of a tibial bypass with resultant restoration of normal circulation. Low-dose intraarterial streptokinase may be the treatment of choice for selected patients who present with thrombosis of a popliteal aneurysm with tibial vessel involvement or with embolic popliteal or tibial artery occlusion.

Acute Disease↗

PubMed1985

Modification of acyl-plasmin-streptokinase complex with polyethylene glycol. Reduction of sensitivity to neutralizing antibody.

Acyl-plasmin-streptokinase complex has advantages as a 'site' directed fibrinolytic agent with the active site protected from the plasma protease inhibitors. But, in clinical use, the fibrinolytic potential of this acyl-enzyme complex is modified or abolished by the presence of streptokinase antibodies in the patients. Therefore, better therapeutic agents are required. In this work, chemical modification of the acyl-plasmin-streptokinase complex with polyethylene glycol was found to result in marked resistance to neutralization with streptokinase antibodies.

Antibodies↗

PubMed1990

Angiographic patency study of anistreplase versus streptokinase in acute myocardial infarction.

128 patients with acute myocardial infarction of duration 6 h or less were randomised in double-blind fashion to receive 30 U anistreplase over 5 min or 1.5 MU streptokinase over 1 h, both intravenously. Angiographic patency was assessed 90 min and 24 h from the start of therapy. 55% of patients who received anistreplase and 53% of patients who received streptokinase had patent infarct-related arteries (TIMI grade 2-3) at 90 min (95% CI 42-68% and 40-66%, respectively). At 24 h 81% and 87.5% of arteries were patent respectively (95% CI, 71-91% and 83.5-91.5%). Time to therapy had no significant effect on patency rates. There was one early reocclusion within 24 h in each treatment group and clinical evidence of reocclusion was recorded between 24 h and hospital discharge in a further 5 patients (streptokinase 3, anistreplase 2). With these regimens, therefore, anistreplase and streptokinase gave the same patency rates.

Adult↗

PubMed1983

Species specificity of streptokinase.

Streptokinase, a bacterial protein, forms a complex with human plasminogen which results in a conformational change in the plasminogen molecule and the exposure of an active center. The plasminogen-streptokinase complex is an activator of plasminogen and is rapidly converted to a plasmin-streptokinase complex which, in the human, is also an activator of plasminogen. Species differences have been found in the reaction of streptokinase with plasminogen varying from no active complex formation at one extreme to the rapid formation of an active activator complex at the other, with resultant differences in rates of complex formation and the yield of plasmin. Explanation of these species differences at a molecular level are discussed as well as the possible application of complex formation in a variety of biological systems as a mechanism to produce variation in enzyme activities in proportion to the concentration of substrate available.

Animals↗

PubMed1989

Effect of streptokinase on left ventricular modeling and function after myocardial infarction: the GISSI (Gruppo Italiano per lo Studio della Streptochinasi nell'Infarto Miocardico) Trial.

It has been shown that streptokinase administration at the time of acute myocardial infarction reduces mortality significantly, and that this reduction in mortality should be related to salvage of jeopardized myocardium and preservation of left ventricular function. To better define the relation between thrombolytic therapy and left ventricular modeling and function after acute myocardial infarction, 331 consecutive patients enrolled in the Gruppo Italiano per lo Studio della Streptochinasi nell'Infarto Miocardico trial were studied by two-dimensional echocardiography just before discharge from the hospital. A 6 month follow-up examination was also available in 232 of these patients. Ventricular volumes were computed from an apical four chamber view, according to a previously published algorithm. An infarct size index was also semiquantitatively assessed, according to the number of akinetic and dyskinetic segments in an 11 segment left ventricular model. At predischarge examination, the 161 patients assigned to streptokinase treatment showed smaller ventricular volumes (end-diastolic volume 119.3 +/- 49.7 versus 134.5 +/- 57.8 ml [p = 0.011]; end-systolic volume 65.4 +/- 36.4 versus 74.9 +/- 45.7 ml [p = 0.036]) and smaller regional wall motion index (2.2 +/- 1.9 versus 2.7 +/- 1.9 segments; p = 0.019) compared with values in the 170 patients assigned to standard care; there was no difference in ejection fraction (46.6 +/- 14.1 versus 45.9 +/- 14.9%; p = 0.64). For both groups of patients, there was a significant relation between end-systolic volume and regional wall motion index (p less than 0.001); for large and similar extents of infarct size, ventricular volume was smaller in patients assigned to thrombolytic treatment than in patients assigned to standard care. At 6 months' follow-up, the differences in volume and regional dysfunction detected at the early examination persisted: 110.8 +/- 47.6 versus 127.9 +/- 53.8 ml for end-diastolic volume (p = 0.001), 56.3 +/- 33.6 versus 69.4 +/- 42.1 ml for end-systolic volume (p = 0.001) and 1.8 +/- 1.8 versus 2.3 +/- 1.8 segments for regional wall motion index (p = 0.001). Again, for comparable extents of infarct size, end-systolic volume was smaller in patients who received streptokinase (n = 110) than in those assigned to conventional treatment (n = 122). It is concluded that streptokinase improves left ventricular modeling and function in patients with myocardial infarction, reducing the extent of regional wall motion abnormalities and lessening postinfarction ventricular dilation. The beneficial effects persist up to 6 months.

Aged↗

PubMed1994

Early angiography cannot predict postthrombolytic coronary reocclusion: observations from the GUSTO angiographic study. Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries.

OBJECTIVES: The purpose of this study was to determine whether early qualitative or quantitative angiographic features can predict reocclusion after initially successful coronary thrombolysis. BACKGROUND: Although both the benefits of early reperfusion and the consequences of subsequent reocclusion after thrombolysis for acute myocardial infarction have been well described, efforts to describe angiographic markers of lesions at high risk for reocclusion have produced conflicting results. The Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO) angiographic trial provides the opportunity to examine these relations in the largest single, prospective patient cohort studied to date. METHODS: We studied 559 patients undergoing follow-up angiography at 90 min and 5 to 7 days after thrombolysis in the GUSTO trial. Patients received one of four thrombolytic regimens: 1) streptokinase with intravenous heparin; 2) streptokinase with subcutaneous heparin; 3) accelerated-dose recombinant tissue-type plasminogen activator (rt-PA) with intravenous heparin; or 4) a combination of streptokinase and conventionally dosed rt-PA with intravenous heparin. Qualitative variables examined at 90-min angiography included Thrombolysis in Myocardial Infarction (TIMI) flow grade, visible thrombus and lesion morphology. Quantitative variables included percent diameter stenosis, percent area stenosis, minimal lumen diameter and lesion length. The study contained a power > 0.85 to detect clinically important differences in percent diameter stenosis, percent area stenosis and minimal lumen diameter between the groups with subsequent reocclusion and sustained patency at the p = 0.05 level. RESULTS: At follow-up, 33 patients (5.9%) had reocclusion. The reocclusion rate for patients with early TIMI grade 2 flow was 6.3% versus 5.6% for TIMI grade 3 flow (p = NS). When the group with reocclusion was compared with the group with continued patency, there were no differences in presence of early visible thrombus, complex lesion morphology, percent diameter stenosis, percent area stenosis, minimal lumen diameter or lesion length. CONCLUSIONS: Our findings demonstrate that neither qualitative nor quantitative angiographic variables at 90 min after initiation of thrombolytic therapy can be used to predict subsequent coronary reocclusion.

Aged↗

PubMed1995

Lessons we have learned from the GUSTO trial. Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Arteries.

Thrombolytic therapy remains a mainstay for the treatment of patients with acute myocardial infarction. This therapy has been the subject of intense investigation and multiple studies as well as substantial controversy. Controversial issues include, among others, the specific drug, need for heparin, the relation between time to treatment and outcome and risk/benefit considerations. The Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO) trial of 41,021 patients addressed many of these issues. The results of the main trial were conclusive--treatment with accelerated tissue-type plasminogen activator (t-PA) resulted in a decreased mortality rate with a 15% reduction (95% confidence interval 5.9 to 21.3) compared with the two streptokinase monotherapy strategies (p = 0.001). Virtually all subgroup analyses, including age, nonanterior infarction location, patients undergoing bypass graft surgery and hypertensive patients, showed remarkable consistency with improved outcome with accelerated t-PA. This reduction in all-cause mortality with accelerated t-PA was associated with a small (absolute 0.2%) but significant increase in hemorrhagic stroke (p = 0.03). A combined end point of death or disabling stroke, or both, was still decreased in the accelerated t-PA group compared with the streptokinase group (p = 0.006). The angiographic substudy evaluated the mechanism of improved outcome and documented that reperfusion therapy works by restoring Thrombolysis in Myocardial Infarction (TIMI) grade 3 flow early, improving left ventricular function and improving mortality. The most favorable outcome seen with t-PA was related to the finding that it resulted in improved TIMI grade 3 flow compared with that for streptokinase.

Age Factors↗

PubMed2005

Streptokinase increases the sensitivity of colon cancer cells to chemotherapy by gemcitabine and cis-platine in vitro.

The aim was to determine the effect of fybrinolytic therapy by streptokinase on chemotherapy and radiation response in human colon cancer cells. The cells were treated with different concentrations of gemcitabine, cis-platine and streptokinase, at a single use or in combinations. Radiation was tested at a dose 0.5, 5 and 15 Gy in three different schedules. The chemotherapy showed higher cytotoxic effect in combination with streptokinase. On the other hand, the combination of chemotherapy with streptokinase and radiotherapy provide no improvement in sensitivity of cancer cells to treatment. The data suggest that fybrinolytic therapy could influence the effect of chemotherapy.

Antineoplastic Agents↗

PubMed1996

Changes in interstitial collagen metabolism during acute myocardial infarction treated with streptokinase or tissue plasminogen activator.

Collagen plays a specific role in the maintenance of vascular integrity and in the thrombosis and scar formation processes. Therefore we found it interesting to study the changes in interstitial collagen metabolism during acute myocardial infarction treated with thrombolytic agents. Changes in collagen synthesis were evaluated by obtaining assays of the serum concentrations of the carboxyterminal propeptide of type I procollagen. Except fibrin plasmin is capable of degrading extracellular matrix components including collagen, and this capability was evaluated by monitoring the serum concentrations of the aminoterminal propeptide of type III procollagen. Twenty-four patients with suspected acute myocardial infarction and indications for thrombolytic therapy were randomized to receive either streptokinase (n = 11) or tissue plasminogen activator (n = 13). The patient groups were identical in their clinical characteristics. Serum levels of the aminoterminal propeptide of type III collagen increased rapidly on infusion of the thrombolytic agents, with the maximal mean increases of 44% and 16% in the streptokinase and TPA-treated groups, respectively. Levels of the carboxyterminal propeptide of type I collagen did not change during the thrombolytic therapy. A transient decrease occurred in the type I propeptide concentration at postinfarction day 2, and this decrease was followed by a secondary increase at days 4 to 6 in both patient groups studied. We conclude that thrombolytic agents stimulate the breakdown of interstitial collagen and that the collagen-degrading activity of TPA is lower than that of streptokinase. This factor may contribute to the relatively higher rethrombosis rate seen after TPA, because exposed collagen in the affected vascular wall stimulates thrombosis formation. On the other hand, increased collagen degradation followed by inhibition of collagen synthesis in the infarcted myocardium might increase the risk for cardiac rupture, especially after streptokinase treatment.

Antithrombins↗

PubMed1999

Efegatran sulfate as an adjunct to streptokinase versus heparin as an adjunct to tissue plasminogen activator in patients with acute myocardial infarction. ESCALAT Investigators.

BACKGROUND: Previous clinical studies have shown that direct antithrombins can accelerate clot lysis after treatment with streptokinase in acute myocardial infarction (MI). Efegatran is a new direct antithrombin, which in experimental animals has been shown to enhance thrombolysis, reduce rate of reocclusion, and limit infarct size. This study was designed to compare the efficacy of efegatran plus streptokinase versus heparin plus accelerated tissue plasminogen activator (TPA) in coronary reperfusion in acute MI. METHODS AND RESULTS: In this randomized, dose-finding study (n = 245), we initially explored 4 doses of efegatran sulfate in combination with streptokinase (1.5 million U) given intravenously within 12 hours of symptom onset. The optimal dosage group of 0.5 mg/kg per hour was expanded and compared with heparin plus accelerated TPA. The primary end point was complete patency (Thrombolysis In Myocardial Infarction [TIMI] grade 3) at 90 minutes after thrombolytic therapy, assessed in a core angiographic laboratory. Infarct-related vessel patency (TIMI grade 2 or 3) and complete patency (TIMI grade 3) were 73% and 40% in the efegatran/streptokinase group versus 79% and 53% in the heparin/TPA group (P = not significant). In-hospital mortality rate was 5% for the efegatran/streptokinase group versus 0% for the heparin/TPA group (P = not significant). Major bleeding occurred in 23% of patients in the efegatran/streptokinase group versus 11% in the heparin/TPA group (P = not significant). No intracranial hemorrhage occurred. CONCLUSIONS: The combination of efegatran plus streptokinase is not superior to the current therapy of heparin and accelerated TPA in achieving early patency. In addition, there is no indication that this experimental treatment can achieve better clinical outcome.

Antithrombins↗

PubMed2002

An independently derived and validated predictive model for selecting patients with myocardial infarction who are likely to benefit from tissue plasminogen activator compared with streptokinase.

BACKGROUND: In the Global Utilization of Streptokinase and tPA for Occluded coronary arteries (GUSTO) trial, patients with myocardial infarction who were treated with tissue plasminogen activator (tPA) had a 6.3% 30-day mortality, compared with a mortality of 7.3% among those treated with streptokinase, despite a greater risk of intracranial hemorrhage with tPA. However, in part because of its higher cost, tPA has not been adopted universally. METHODS: Using an independently developed model, we predicted the benefits of tPA therapy in the 24,146 patients in the GUSTO trial and compared these predictions with the actual benefits of tPA, after classifying patients by their risks of mortality and intracranial hemorrhage. We also performed a "patient-specific" cost-effectiveness analysis among different strata of expected benefit of tPA. RESULTS: Our model predicted that among patients with myocardial infarction, 61% of the benefit of tPA use in reducing mortality accrued to only 25% of patients; treating half of patients could capture 85% of the benefit. Including the risk of intracranial hemorrhage, our model predicted that treating half the GUSTO patients with tPA and the others with streptokinase would yield similar outcomes as treating all patients with tPA, because the additional risk of intracranial hemorrhage exceeded the expected benefit in some patients. When patients were stratified into quartiles of risk, the observed outcomes in the GUSTO patients corresponded well with these predicted results. The estimated cost-effectiveness of tPA was sensitive to patient characteristics. CONCLUSION: For selected patients, use of tPA yields substantially better outcomes than streptokinase, and use of the less expensive agent is difficult to justify. For many patients, however, tPA is unlikely to provide any additional benefit and, in some patients, it may even cause net harm.

Adult↗

PubMed1984

Myocardial infarction management with peripheral streptokinase.

The early management of myocardial infarction (MI) is undergoing a new evolution. Aggressive treatment and new invasive modalities have brought improved prognosis to these patients. Intracoronary administration of fibrinolytic agents is rapidly gaining wide acceptance. We report a pilot protocol for administration of peripheral intravenous (IV) versus direct intracoronary fibrinolytic agents in acute MI. Thirty patients with acute evolving MI were assigned consecutively to receive fibrinolytic therapy; 15 patients received intracoronary streptokinase and 15 received peripheral IV streptokinase at a dosage of 1.5 million units over a 30-minute period. Evaluation by clinical symptoms, ECG changes, and hemodynamic studies by angiography and radionuclide ventriculography indicated comparable and beneficial results for both groups. Patients assigned to the IV therapy were able to receive streptokinase therapy 1.5 hours earlier than those receiving intracoronary therapy, and they had a higher incidence of reperfusion. We conclude that IV streptokinase therapy may be preferable to intracoronary therapy in view of a higher reperfusion frequency, fewer complications, and greater ease of administration. With both treatment modalities, comparable improvement in left ventricular function was noted. Institutions that do not have invasive techniques available may well be the first to benefit from this method of myocardial salvage, and we encourage cooperation between emergency and cardiology departments.

Adult↗

PubMed1985

Effective use of streptokinase for peritoneal catheter failure.

The fibrinolytic enzyme streptokinase (streptase) was infused into the peritoneal catheter in 19 episodes of catheter failure in 16 patients. Intraabdominal bleeding prior to infusion was seen in seven of these episodes. Fibrin strands and clots were present in four additional successful cases. Streptokinase successfully relieved the obstruction in 13 episodes in 11 patients. The procedure failed in two cases of omental ingrowth and in another with catheter malposition. Streptokinase infusion also failed in two patients with Pseudomonas aeruginosa and one patient with Staphylococcus epidermidis peritonitis. Intraperitoneal streptokinase infusion is simple and free of side effects. Its use should be considered in peritoneal catheter failure, particularly in cases where bleeding or fibrin accumulation may play a role.

Adult↗

PubMed1983

Systemic versus intracoronary streptokinase infusion in the treatment of acute myocardial infarction.

Clinically encouraging results can be obtained with an intravenous high dose short-time infusion of streptokinase in patients with evolving myocardial infarction. The feasibility and efficacy of the intracoronary and the systemic approach of streptokinase therapy in acute myocardial infarction are discussed in this report and include topics such as infarct artery recanalization success rate, coronary thrombus lysis time, benefit for patients with subtotal coronary occlusion, reocclusion rate, the necessity of additional surgical interventions, salvage of ischemic myocardium and side effects. The value of high dose intravenous short-time streptokinase infusion needs to be assessed with properly designed clinical trials against the background afforded by the results observed with direct intracoronary streptokinase infusion.

Cardiac Catheterization↗

PubMed1987

Activation of the fibrinolytic system during intracoronary streptokinase administration.

Serial biochemical studies were performed in 12 patients treated with intracoronary streptokinase infusion for acute myocardial infarction, in order to study the method of activation of the fibrinolytic system during local administration of a relatively low dose of this drug and to determine correlations between systemic effects and reperfusion. Plasma samples were obtained before and every 15 minutes during the infusion of streptokinase and after completion of the therapy. Streptokinase dosage in this study was 211,000 +/- 88,000 IU (+/- SD). The average time from the onset of symptoms to the start of infusion was 2 hours 50 minutes (range 1 hour 10 minutes to 3 hours 30 minutes). Reperfusion occurred in six patients and temporary recanalization in three; in three patients no recanalization was achieved. Fibrinolytic assays of pretreatment plasma samples revealed elevated levels of plasminogen activators, presumably caused by the release of tissue-type plasminogen activator after a condition of stress. Plasminogen concentrations decreased from 94 +/- 17% to 44 +/- 30%. Alpha 2-antiplasmin fell from 84 +/- 27% to 12 +/- 19%; in seven patients no plasmin inhibitor activity was measurable at the completion of the infusion. Free plasmin occurred in samples only when this inhibitor had disappeared. This resulted in a lytic state leading to degradation of fibrinogen, the levels of which fell from 2.9 +/- 0.7% to 1.5 +/- 1.1%. Fibrinogen degradation products, measured in plasma with monoclonal antibodies, increased exponentially during streptokinase infusion in at least four patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary Vessels↗

PubMed1998

Comparative efficacy of a two-hour regimen of streptokinase versus alteplase in acute massive pulmonary embolism: immediate clinical and hemodynamic outcome and one-year follow-up.

OBJECTIVES: This study sought to compare the efficacy of 2-h regimens of alteplase and streptokinase in acute massive pulmonary embolism. The primary end point was immediate hemodynamic improvement, and secondary end points included early clinical efficacy and safety, as well as 1-year clinical outcome. BACKGROUND: Several thrombolytic regimens have been compared for the past 10 years in randomized studies, showing that 2-h infusion regimens of alteplase or urokinase lead to faster hemodynamic improvement than former 12- to 24-h administration protocols in acute massive pulmonary embolism. Many trials have focused on immediate hemodynamic and angiographic outcomes, but none has addressed long-term follow-up after thrombolysis. METHODS: Sixty-six patients with acute massive pulmonary embolism (Miller score > 17 and mean pulmonary artery pressure >20 mm Hg) were randomly assigned to receive either a 100-mg 2-h infusion of alteplase (n = 23) or 1.5 million IU of streptokinase over 2 h (n = 43). In both groups, heparin infusion was started at the end of thrombolytic infusion and adapted thereafter. Total pulmonary resistance was monitored over a 12-h period. Pulmonary vascular obstruction was assessed 36 to 48 h after thrombolytic therapy. One-year follow-up information included death, cause of death, recurrent pulmonary embolism, chronic thromboembolic pulmonary hypertension, stroke and bleeding. RESULTS: Both groups had similar baseline angiographic and hemodynamic characteristics of severity, with maintained cardiac output in 64 (97%) of 66 patients. The results (mean +/- SD) demonstrated that despite a faster total pulmonary resistance improvement observed at 1 h in the alteplase group compared with the streptokinase group (33+/-16% vs. 19 16%, p = 0.006), a similar hemodynamic efficacy was obtained at 2 h when both thrombolytic regimens were completed (38+/-18% vs. 31+/-19%). There was no significant difference in either pulmonary vascular obstruction at 36 to 48 h or bleeding complication rates. One-year event-free survival was similar in both groups, as most events were related to concomitant diseases. CONCLUSIONS: These results suggest that a 2-h regimen of streptokinase can be routinely used in patients with massive pulmonary embolism and maintained cardiac output without obviously compromising efficacy or safety.

Acute Disease↗

PubMed1999

Survival 12 years after randomization to streptokinase: the influence of thrombolysis in myocardial infarction flow at three to four weeks.

OBJECTIVES: The purpose of this study was to determine whether the mortality benefit of intravenous streptokinase administered within 4 h of the onset of acute myocardial infarction is maintained at 12 years, and whether Thrombolysis in Myocardial Infarction (TIMI) flow grades independently influence late survival. BACKGROUND: Treatment with reperfusion therapies and achievement of TIMI 3 flow are associated with increased short- and medium-term survival after infarction. Whether infarct artery flow independently influences survival more than five years after infarction is unknown. METHODS: The late survival of patients randomized to receive either streptokinase (1,500,000 IU over 30 to 60 min) or a matching placebo within 4 h of symptom onset in 1984-1986 was determined. Angiography was performed in surviving patients at three to four weeks, and TIMI flow grades were assessed blind to randomization and outcomes. The late vital status was determined in 99% of patients. RESULTS: Patients randomized to receive streptokinase (n = 107) had improved survival compared with those randomized to placebo (n = 112) at five years (84% vs. 70%; p = 0.023) and 12 years (66% vs. 51%; p = 0.022). At five years 94% of patients with TIMI grade 3 flow, 81% of those with TIMI grade 2 flow and 72% of those with TIMI grade 0-1 flow survived (p = 0.005). At 12 years 72% of patients with TIMI 3, 67% of those with TIMI 2 and 54% of those with TIMI 0-1 flow survived (p = 0.023). Multivariate analysis identified the ejection fraction (p = 0.014), exercise duration (p = 0.013) and TIMI 3 flow (p = 0.04 compared with TIMI 0-2 flow) as important factors for five-year survival. At 12 years multivariate predictors of late survival were the ejection fraction (p = 0.006), exercise duration (p = 0.003) and myocardial score (p = 0.013). The end-systolic volume index was similar to the ejection fraction as a predictor of survival at five and 12 years. CONCLUSIONS: The survival benefits of streptokinase persist for 12 years after infarction. TIMI flow at three to four weeks is an independent predictor of five-year survival.

Actuarial Analysis↗

PubMed1999

Recombinant hirudin (lepirudin) for the improvement of thrombolysis with streptokinase in patients with acute myocardial infarction: results of the HIT-4 trial.

OBJECTIVES: The purpose of this study was to compare recombinant hirudin and heparin as adjuncts to streptokinase thrombolysis in patients with acute myocardial infarction (AMI). BACKGROUND: Experimental studies and previous small clinical trials suggest that specific thrombin inhibition improves early patency rates and clinical outcome in patients treated with streptokinase. METHODS: In a randomized double-blind, multicenter trial, 1,208 patients with AMI < or =6 h were treated with aspirin and streptokinase and randomized to receive recombinant hirudin (lepirudin, i.v. bolus of 0.2 mg/kg, followed by subcutaneous (s.c.) injections of 0.5 mg/kg b.i.d. for 5 to 7 days) or heparin (i.v. placebo bolus, followed by s.c. injections of 12,500 IU b.i.d. for 5 to 7 days). A total of 447 patients were included in the angiographic substudy in which the primary end point, 90-min Thrombolysis in Myocardial Infarction (TIMI) flow grade 3 of the infarct-related artery, was evaluated, while the other two-thirds served as "safety group" in which only clinical end points were evaluated. As an additional efficacy parameter the ST-segment resolution at 90 and 180 min was measured in all patients. RESULTS: TIMI flow grade 3 was observed in 40.7% in the lepirudin and in 33.5% in the heparin group (p = 0.16), respectively. In the entire study population the proportion of patients with complete ST resolution at 90 min (28% vs. 22%, p = 0.05) and at 180 min (52% vs. 48%, p = 0.18) after start of therapy tended to be higher in the lepirudin group. There was no significant difference in the incidence of hemorrhagic stroke (0.2% vs. 0.3%) or total stroke (1.2% vs. 1.5%), reinfarction rate (4.6% vs. 5.1%) and total mortality rate (6.8% vs. 6.4%) at 30 days, as well as the combined end point of death, nonfatal stroke, nonfatal reinfarction, rescue-percutaneous transluminal coronary angioplasty and refractory angina (22.7 vs. 24.3%) were not statistically different between the two groups. CONCLUSIONS: Lepirudin as adjunct to thrombolysis with streptokinase did not significantly improve restoration of blood flow in the infarct vessel as assessed by angiography, but was associated with an accelerated ST resolution. There was no increase in the risk of major bleedings with lepirudin compared to heparin.

Adult↗