Are the various thrombolytic agents equally effective in the treatment of acute transmural myocardial infarction?

While it is no longer possible to imagine the treatment of an acute transmural myocardial infarction without the use of thrombolytic agents, some discussion still exists as to the choice of the thrombolytic agent. Our study concerns a group of 160 patients with an acute transmural myocardial infarction, 60 of whom were treated with anistreplase, 52 with streptokinase and 48 with alteplase. Statistically, the administration of anistreplase was associated with a significantly higher frequency of ventricular arrhythmias in comparison to the other thrombolytic agents, whereas after subsequent coronary angiography, the anistreplase group revealed a significantly lower number of completely occluded coronary arteries. The data from this study demonstrate that anistreplase is a very valuable thrombolytic agent. It may even be more effective than streptokinase and alteplase in the treatment of acute myocardial infarction when the patency of the coronary arteries 1 month after the acute coronary event is considered the primary endpoint.     

An overview of the patency and stroke rates following thrombolysis with streptokinase, alteplase, and anistreplase used to treat an acute myocardial infarction

The results of an overview of early (90-240 min) and late (24 hours or more) patency and of stroke rates for each of the three commercially available thrombolytic agents, streptokinase, alteplase, and anistreplase are presented. Studies included in this analysis are all those published between 1985 and March 1992 and focus on the licensed dosage regimens of each agent. The rates of early and late patency for streptokinase were 64.7% and 80.8%; for alteplase, 66.6% and 73.7%; and for anistreplase, 72.1% and 84.5%. The rates of total and hemorrhagic stroke for streptokinase were 0.69% and 0.17%; for alteplase, 1.27% and 0.50%; and for anistreplase 0.91% and 0.38%. These results provided evidence that the rates of early and late patency appeared to be greatest for anistreplase and that the rates of stroke are within "acceptable" ranges for all three thrombolytic agents with streptokinase affording the lowest rate.     

Importance of the pharmacological profile of thrombolytic agents in clinical practice.

Three thrombolytic agents are frequently used in the United States for treating patients with acute myocardial infarction: streptokinase, alteplase (tissue plasminogen activator [t-PA]), and anistreplase (anisoylated plasminogen-streptokinase activator complex [APSAC]). A fourth agent, urokinase, is occasionally used but clinical experience is considerably more limited with this agent. Streptokinase, alteplase, and anistreplase differ in a number of pharmacologic properties, which include half-life, enzymatic efficiency, and induction of platelet aggregation; these differences may be clinically important. For example, anistreplase and alteplase have high affinity for fibrin and bind to intravascular thrombi after intravenous administration, which may result in higher clot specificity. Anistreplase has the longest half-life of the 3 agents and, therefore, can be administered conveniently and quickly. Alteplase has a shorter half-life and heparin is generally a necessary adjunctive agent. These differences can be clinically significant in various settings and application of such theoretical advantages is just beginning.     

Use of left ventricular function as an end point of thrombolytic therapy.

In recent acute myocardial infarction, early reperfusion of the infarct-related artery by intracoronary or intravenous thrombolytic therapy induces a significant limitation of infarct size, provided reperfusion occurs within a time frame that myocardial salvage can still be expected. Limitation of infarct size reduces scar tissue formation, aneurysm formation, infarct zone expansion, left ventricular volume enlargement, and eventually results in higher left ventricular ejection fraction. Infarct size limitation and left ventricular function preservation occur with all thrombolytic agents currently in clinical use: streptokinase, alteplase and, more recently, anistreplase. When anistreplase is compared with conventional heparin therapy, a 31% reduction in infarct size is found (estimated from single photon emission computed tomography, or SPECT). This translates into a significant preservation of left ventricular ejection fraction as observed in anistreplase-treated patients compared with heparin-treated patients (0.53 +/- 0.13 vs 0.47 +/- 0.12, p less than 0.002). In comparative trials of 2 thrombolytic agents, anistreplase was demonstrated to be as efficient as alteplase on left ventricular ejection fraction preservation and infarct size limitation.     

Advances in thrombolytic therapy

Summary Alteplase and saruplase are more fibrin-specific thrombolytic drugs than anistreplase. These and the thrombolytic drugs of the first generation (streptokinase and urokinase) have shortcomings and limitations. The prolonged intravenous maintenance infusions have been replaced by a bolus injection, accelerated infusions, or the combined intravenous administration of thrombolytic agents. Numerous truncated alteplase or saruplase molecules have been constructed by deletion and domain substitution or hybrids made of the two molecules without gaining in thrombolytic potency. Recombinant staphylokinase and plasminogen activator from bat saliva have some interesting properties and are being investigated. Thrombus-targeted thrombolytic drugs were constructed using monoclonal antibodies against fibrin fragments or against epitopes of activated platelets. Fibrin-specific thrombolytic drugs require the concomitant use of a potent antithrombotic drug to prevent reocclusion. Whether hirudin or synthetic thrombin inhibitors are superior to heparin and whether novel antiplatelet agents, including monoclonal antibodies to platelet receptors and disintegrins, are more effective than aspirin is under clinical investigation. The place of stable analogues of prostacyclin during thrombolytic treatment is still unsettled.     

Overview of patency as an end point of thrombolytic therapy.

Underlying the use of thrombolytic therapy is the hypothesis that reestablishment and maintenance of coronary blood flow (coronary patency) are the primary mechanisms of therapeutic benefit in patients with acute myocardial infarction. Early achievement and maintenance of adequate coronary blood flow (patency) in the infarct-related artery are the primary goals of thrombolytic therapy. One third of patients may achieve spontaneous patency within a few days following acute myocardial infarction. When antithrombotic therapy (i.e., heparin) is administered, this rate increases to greater than 50%, but patency is achieved only gradually and mortality reductions comparable to thrombolytic therapy are not achieved. After administration of a thrombolytic agent, early (90-minute) patency rates are greater with alteplase or anistreplase than with streptokinase. However, patency rates for alteplase decline by 10-30% if intravenous heparin is not given concurrently. When patency is assessed greater than 24 hours following thrombolytic therapy, no significant difference exists among the agents. A single angiographic observation of the artery at 90 minutes, although useful, may be inadequate to distinguish among the beneficial clinical effects of different thrombolytic regimens. The overall reperfusion or patency profile is probably a better basis for assessing relative benefits. Intravenous thrombolytic regimens that are increasingly effective in rapidly achieving and maintaining coronary patency are now available and in further development.     

Cost effectiveness of thrombolytic treatment for myocardial infarction: comparison of anistreplase, alteplase and streptokinase in 270 patients treated within 4 hours

Two hundred and seventy patients, under 71 years of age andsuffering from a less than 4 h infarction diagnosed accordingto clinical and electrocardiographic criteria, were included.two 90-patient groups were randomized and then treated witheither anistreplase (30 mg iv over 5 min) or alteplase (10 mgbolus injection + 5000 IU heparin bolus injection, followedby 90 mg alteplase over 3 h), and compared with a consecutivecontrol series of 90 patients treated with streptokinase (1.5million U over 1 h). Intravenous heparin and aspirin (250 mgday^–1) were then prescribed routinely. The three groupswere comparable as regards age (55.2±10 years), male/femaleratio (10.4 the site of the infarction (42% anterior, 55% inferior)and initial clinical seriousness (Killip I=90%, II=8%, III=2%).The patients were thombolysed in 17 community hospitals, andthen referred to a university hospital with catheterizationfacilities. An efficacy score was determined, based on fourparameters: two obtained from coronary angiography and leftventriculography performed on day 6±2 (N = 252) (asynergicscore and patency of the infarct-related artery), one from Tl-tomographyperformed at rest (infarct size) and one from radionuclide angiography(global left ventricular ejection fraction) performed betweenday 15 and day 21 (N = 242). The score (range: 0–24 perpatient) was 17.8±6.4 for alteplase, 17.7±6.0for anistreplase and 18.1±6.0 for streptokinase respectively(NS). The real cost of the hospital phase, for each patient,was determined by adding up the cost of thrombolytic treatment(ranging from 1.7% of the total hospital cost for streptokinaseto 16% for alteplase), other treatment and biological examinations(10% of the total cost), coronary angiography, followed in 35%of patients by angioplasty (21% of the overall cost) and hospitalization(ranging from 49% of the total cost for alteplase and anistreplaseto 56% for streptokinase [NS] for an average 17-day hospitalization.Thus, the total cost of the hospital phase was 6460 ECU foralteplase, 6570 ECU for anistreplase and 6050 ECU for streptokinase(NS). The cost/efficacy ratio was 548 ECU for alteplase, 570ECU for anistreplase and 405 ECU for streptokinase. Secondarymortality and re-infarction rates were very low (1.2% and 1.5%respectively) after 1 year following the treatment. However,ischaemia recurred in 23% of patients, requiring revascularizationoperations in 9% of them. Sixty-nine per cent of patients withprofessional occupations were able to resume these activities. This study showed no difference in efficacy between the threethrombolytic agents for the three left ventricular parameters(left ventricular ejection fraction, asynergic score, necroticmass) and for the patency of the infarct-related artery, andalso demonstrated that the cost of the thrombolytic agent hadrelatively little effect on the total cost of myocardial infarction.There could be a potential saving by shortening hospitalization,which accounted for half the cost of thrombolysed myocardialinfarction.     

Thrombolytic therapies: the current state of affairs.

Thrombotic occlusive diseases are manifested in several disorders that have significant morbidity and mortality, including acute myocardial infarction, pulmonary embolism, deep venous thrombosis, and cerebrovascular accidents. This review summarizes the recently published literature covering thrombolytic therapies in these diseases, with particular attention to comparisons between the fibrin-specific tissue plasminogen activators (alteplase, reteplase, and tenecteplase) and the nonfibrin-specific activators (streptokinase or urokinase plasminogen activator). These agents act to convert plasminogen to plasmin, which in turn cleaves fibrin as part of the lysis process. Fibrin-specific activators were anticipated to be more efficacious and safer than nonspecific agents in thrombolytic occlusive diseases because of their pathophysiologically restricted mechanism of action. However, the fibrin-specific activators also lyse physiological hemostatic plugs, which can result in costly adverse events. Efficacy of fibrin-specific tissue plasminogen activators has been shown to be generally equivalent, with similar mortality rates compared with nonspecific agents; however, fibrin-specific agents may be associated with an increased incidence of intracerebral hemorrhage and with increased costs. Therefore, it appears that given equivalent efficacy, nonfibrin-specific activators, such as streptokinase or urokinase, may be a safer choice in many thrombotic situations.     

Thrombolysis, anticoagulation, and reocclusion.

Based on apparent higher recanalization rates of the infarct-related artery, preferential use of thrombolytic agents with high clot specificity has been proposed for treating patients with acute myocardial infarction. In the Thrombolysis in Myocardial infarction (TIMI-I) and European Cooperative Group studies, higher reperfusion rates were observed with alteplase compared with streptokinase, causing many to assume that the former would achieve a greater reduction in early hospital mortality. However, the Gruppo Italiano per lo Studio della Streptochinasi nell'Infarto Miocardico (GISSI-2) and its associated International Study Group failed to show any differences in 15-day mortality between these agents in more than 20,000 patients. This apparent lack of correlation between reperfusion rates and early mortality may be explained in part when one considers that recanalization or patency rates measured at a given point in time, such as 90 minutes after onset of therapy, fail to define the subsequent vessel status. Early reocclusion is the major reason for this and is a major limitation to the clinical efficacy of thrombolytic drugs. Following recanalization, residual fibrin-bound thrombin adherent to the site of arterial injury from plaque rupture strongly promotes rethrombosis. Although antiplatelet and antithrombin agents such as aspirin and heparin help to decrease rethrombosis, these agents are far from ideal. Thrombolytic agents that produce a significantly prolonged systemic thrombolytic state, such as streptokinase and anistreplase, are likely to result in less rethrombosis. Therefore, a systemic fibrinolytic state would appear to be an advantage rather than a disadvantage, particularly because the incidence of intracerebral hemorrhage does not appear to be greater with their use compared with agents producing less systemic fibrinolysis.(ABSTRACT TRUNCATED AT 250 WORDS)     

Short- and long-term comparative study of anistreplase versus streptokinase in acute myocardial infarction.

Streptokinase is well established as an effective thrombolytic. Anistreplase, a new thrombolytic drug, is a complex of streptokinase and acylated human plasminogen that can be administered by intravenous bolus and activates plasminogen at the clot site. Although both streptokinase and anistreplase are effected in treating myocardial infarction (MI), they have different pharmacologic properties. This study was designed to identify short- and long-term differences in their clinical effectiveness, safety in use, and survival rates in patients with acute MI. One hundred ten successive patients under seventy years of age admitted within three hours after onset of sustained chest pain suggestive of acute MI were randomized to receive either 30 units of anistreplase intravenously over five minutes or intravenous injection of 750,000 units of streptokinase over thirty to sixty minutes. Reperfusion was achieved in 34 of the 52 (65%) patients treated with anistreplase and in 41 of the 58 (71%) patients treated with streptokinase (p = NS). The two drugs were equally effective in preserving left ventricular ejection fraction, which was found to be significantly better in patients with anterior wall MI who had achieved reperfusion than it was in those who did not (p less than 0.02). One-month, twelve-month, and thirty-six-month survival rates were high (96% to 88%) with no significant difference between the two treatment groups. The authors conclude that the two drugs are equally effective thrombolytic agents but that anistreplase has the advantage that it can be administered as a bolus injection.     

Unresolved issues in the thrombolytic treatment of myocardial infarction.

Despite enormous advances made in understanding of the biochemistry of fibrinolytic agents and their extensive clinical use in acute myocardial infarction a number of unresolved issues remain. There is an intriguing divergence of left ventricular response and reduction of mortality in patients with acute myocardial infarction treated with thrombolytic drugs. It is also difficult to explain why patients treated late have a reduced mortality after thrombolytic treatment. Uncertainty prevails on the validity of thrombolysis in patients with a low and very high risk of mortality. Resistance of coronary occlusion to any thrombolytic is another unexplained fact. Alteplase and saruplase are more fibrin-specific thrombolytic drugs than anistreplase. These and the thrombolytic drugs of the first generation (streptokinase and urokinase) have shortcomings and limitations. It is being explored whether prolonged intravenous maintenance infusions are more effective if replaced by a bolus injection, accelerated infusion or the combined intravenous administration of thrombolytic agents.     

Saruplase in myocardial infarction

Saruplase is an unglucosylated single-chain recombinant urokinase-type plasminogen activator. Dose finding studies in patients with acute myocardial infarction indicated that a dose of 80 mg of saruplase, given as a bolus of 20 mg and iv infusion of 60 mg in one hour, led to excellent patency figures.Saruplase is most effective when combined with a bolus of 5000 IU heparin followed by an iv heparin infusion for at least 24 hours.When saruplase is compared to other thrombolytic agents (streptokinase, alteplase, urokinase), it becomes apparent that its profile is excellent. Early patency rates are at least comparable to alteplase. Further reocclusion rates of saruplase after one day are lower than those of streptokinase and alteplase. Patency rates 24–72 hours after start of medication are comparable between saruplase and urokinase.The large database in over 6000 patients shows that saruplase, in comparison to the other thrombolytic agents, is safe. Its bleeding complication rate is significantly lower than streptokinase, and a trend to lower in-hospital mortality is observed when compared to urokinase.Summarizing, when comparing to the presently available thrombolytic agents, saruplase is a fast acting, effective and safe thrombolytic agent.     

Clinical risks of thrombolytic therapy.

Understanding the clinical risks of intravenous thrombolytic therapy is critical to appropriate patient selection. The major risks can be classified into 5 major categories: intracranial hemorrhage, systemic hemorrhage, immunologic complications, hypotension, and myocardial rupture. Although theoretical concern exists about thromboembolic complications, they rarely occur. Although cardiac rhythm disturbances are somewhat more likely to occur at the time of reperfusion, the clinical significance of "reperfusion arrhythmias" is minimal. Intracranial hemorrhage, the most devastating complication, occurs in 0.2-1% of patients treated with thrombolytic therapy. Factors associated with incremental risk are now being identified from large clinical trials. Systemic hemorrhage is uncommon in patients without major vascular punctures and seldom leads to serious adverse outcomes. Immunologic complications--including anaphylaxis, which is rare, and immune complex disease, which is more common--occur only with streptokinase or agents with a streptokinase moiety, including anistreplase (anisoylated plasminogen--streptokinase activator complex, APSAC). Hypotension, which can be managed easily in most patients, is also observed much more frequently with streptokinase and anistreplase. Myocardial rupture is increasingly being recognized as a possible complication of late thrombolysis. A proper perspective on clinical risk can only be gained in the context of potential benefit of therapy. In many cases individual patients considered to be at highest risk for complications also stand to gain the most from treatment. Many of the questions raised by currently available data about bleeding risk are being addressed in the ongoing Global Utilization of t-PA and Streptokinase (GUSTO) Trial. A paradigm for considering this decision making problem is presented.     

Efficacy of thrombolytic agents in the treatment of pulmonary embolism.

Recent guidelines recommend bolus-dose alteplase for treating massive pulmonary embolism (PE). However, the safest and most effective treatment is as yet unknown. In the present study, a meta-analysis of published studies of alteplase infusion, bolus-dose alteplase and streptokinase was performed. The outcome measures were as follows: objective assessment of thrombolysis; all-cause mortality; deaths due to initial PE, major bleeding episodes and recurrent PE; and morbidity. In total, 26 studies were identified; however, only two comparative studies of alteplase infusion versus either bolus-dose alteplase or streptokinase were found. Meta-analysis revealed no significant difference between the three regimens, but was compromised by a paucity of data. Crude analysis of summated data on thrombolytic efficacy from all studies revealed that alteplase infusion was more effective than bolus-dose alteplase (relative risk (RR): 1.95; 95% confidence interval (CI): 1.19-3.2), whereas streptokinase was more effective than alteplase infusion (RR: 1.27; 95% CI: 1.09-1.47). Alteplase infusion had a lower mortality due to the initial PE than both bolus-dose alteplase and streptokinase (RR: 0.16; 95% CI: 0.05-0.59 and RR: 0.13; 95% CI: 0.04-0.46, respectively). In conclusion, this evidence suggests that the three thrombolytic agents may vary in efficacy. However, large-scale randomised controlled trials are needed to confirm these results.     

Multicenter patency trial of intravenous anistreplase compared with streptokinase in acute myocardial infarction. The TEAM-2 Study Investigators

Thrombolytic therapy has been shown to improve clinical outcome when administered early after the onset of symptoms of acute myocardial infarction; the mechanism of benefit is believed to be reestablishment and maintenance of coronary artery patency. Anistreplase is a second generation thrombolytic agent that is easily administered and has a long duration of action. To compare anistreplase (30 units/2-5 min) and therapy with the Food and Drug Administration-approved regimen of intravenous streptokinase (1.5 million units/60 min), a randomized, double-blind, multicenter patency trial was undertaken in 370 patients less than 76 years of age with electrocardiographic ST segment elevation who could be treated within 4 hours of symptom onset. Coronary patency was determined by reading, in a blinded fashion, angiograms obtained early (90-240 minutes; mean, 140 minutes) and later (18-48 hours; mean, 28 hours) after beginning therapy. Early total patency (defined as Thrombolysis in Myocardial Infarction grade 2 or 3 perfusion) was high after both anistreplase (132/183 = 72%) and streptokinase (129/176 = 73%) therapy, and overall patency patterns were similar, although patent arteries showed "complete" (grade 3) perfusion more often after anistreplase (83%) than streptokinase (72%) (p = 0.03). Similarly, residual coronary stenosis, determined quantitatively by a validated computer-assisted method, was slightly less in patent arteries early after anistreplase (mean stenosis diameter, 74.0%) than streptokinase (77.2%, p = 0.02). In patients with patent arteries without other early interventions, reocclusion risk within 1-2 days was defined angiographically and found to be very low (anistreplase = 1/96, streptokinase = 2/94). Average coronary perfusion grade was greater, and percent residual stenosis was less, at follow-up than on initial evaluation and did not differ between treatment groups. Enzymatic and electrocardiographic evolution was not significantly different in the two groups. Despite rapid injection, anistreplase was associated with only a small (4-5 mm Hg), transient (at 5-10 minutes) mean differential fall in blood pressure. In-hospital mortality rates were comparable for anistreplase and streptokinase (5.9%, 7.1%). Stroke occurred in one (0.5%) and three (1.6%) patients, respectively; one stroke was hemorrhagic. Other serious bleeding events and adverse experiences occurred uncommonly and with similar frequency in the two groups. Thus, for the end points of our study (patency, safety), anistreplase and streptokinase showed overall favorable and relatively comparable outcomes, with a few differences.(ABSTRACT TRUNCATED AT 400 WORDS)     

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.     

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.     

Effect of thrombolytic therapy on parameters of endothelial function in patients with myocardial infarction

THE AIM OF STUDY: A comparative estimation of influence various thrombolytic preparations(alteplase, Streptokinase) on clinical course and the remote forecast of disease, and also of parameters of a metabolism of nitric oxide of the patient with acute myocardial infarction. MATERIAL AND METHODS: In research have included 70 patients with acute myocardial infarction (MI) with rise of segment ST. Patients have been divided into groups depending on a kind of applied thrombolytic agent. Estimated features of clinical current by MI in both groups of patients , year forecast of disease, parameters of a metabolism nitric oxide and oxidative stress and antioxidative defence during the acute period of MI. RESULTS: Greater efficiency thrombolytic therapies is revealed in group of patients with application of alteplase. The patients in group of alteplase were characterised by more favorable current both acute and remote periods of MI. In these patients more significant activation of parameters of oxidative stress is revealed, than in group of application of streptokinase. This is caused by more effective revascularisation and reperfusion of myocardium. In group of patients treat with the streptokinase decrease in the level of stable metabolites of nitric oxide is more marked, than in group of patients with alteplase. Statistically significant increase of this parameters is revealed in group with endothelial protection by alteplase. CONCLUSION: Advantages of the tissue plasminogen activator alteplase concerning influence on clinical course of the acute period of MI and the remote forecast are shown, that, apparently is connected not only with greater frequency of effective revascularisation of a myocardium, but also with optimization of endothelial functions of patients with MI.     

Changes in mortality of acute myocardial infarction as a function of a changing treatment during the last two decades

Forty years ago, after the establishment of coronary care units, a significant decrease in mortality of acute myocardial infarction was noted. Twenty years ago, the break-through of thrombolysis realized once again a significant decrease in mortality. In this study we compare, in a rather small community hospital, the mortality and safety of thrombolytic therapy in acute myocardial infarction with a more conventional, conservative medical therapy. We examined all cases of acute myocardial infarction between 1978 up to 1998 inclusive, concerning treatment and mortality rate after a six month period. To be included in the study, acute myocardial infarction had to fulfill particular inclusion criteria. A total of 1863 cases of acute myocardial infarction were included. The mortality rate of patients with acute myocardial infarction treated with thrombolytic agents was strikingly lower and statistically very significantly different (p < 0.001) in comparison with the mortality rate of patients treated with heparin or coumarine derivatives. The mortality rate dropped from 10.57% in the coumarine group and from 14.95% in the heparin group to 5.41% in the alteplase group, to 4.95% in the anistreplase group and 4.00% in the streptokinase subgroup. The complications directly connected to the treatment did not seem to be different between the five groups, and they were also not more frequent by using thrombolytic agents. In the last 20 years, better preventive measures (life habits, diet, medication) and trials to better control the risk factors have not influenced greatly the average amount of cholesterol in patients with an acute myocardial infarction. Also the percentage of patients with high blood pressure has hardly decreased over the last 20 years. The mortality associated with acute myocardial infarction has decreased significantly with the use of thrombolytics. In most cases, thrombolytics are administered routinely and safely. In this way, they are the first choice therapy for myocardial infarction in smaller hospitals. To obtain excellent coronary patency, thrombolytic agents with a long half-life and with PAI-1 resistance are required in the future. The current measures and medical therapies seem to be insufficient to control the risk factors for coronary atherosclerosis.