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PubMed1995

Prehospital thrombolysis in rural emergency room and subsequent transport to a coronary care unit: Ravenna Myocardial Infarction (RaMI) trial.

OBJECTIVE: To assess the feasibility, safety and efficacy of thrombolysis in the Emergency Room of a Rural Hospital with no Coronary Care Unit, and subsequent transfer to the Coronary Care Unit of a City Hospital. DESIGN: Prospective study, controlled with two parallel groups of consecutive patients (Group 1: Rural Hospital, Group 2: CCU Ravenna) and administration of Anistreplase 30 intravenous unit. SETTING: Rural Emergency Rooms which transmitted the electrocardiogram by cardiotelephone to the Ravenna Coronary Care Unit (average distance 35 km; range: 17-50 km). PATIENTS: 280 (Group 1: 102 patients, Group 2: 178 patients) with suspected acute myocardial infarction and with no contra-indications to fibrinolysis, within 6 h of onset of symptoms. MAIN OUTCOME MEASURES: time saving, accuracy of diagnosis, adverse events, left ventricular function and survival. RESULTS: the median pain to needle time was 90' in Group 1 and 165' in Group 2 (P < 0.001). Accuracy of diagnosis for acute myocardial infarction was 91% and 100%, respectively. Complications were rare and none occurred during transfer. The creatine phosphokinase peak of Group 1 was lower than Group 2 (1389 vs. 2186 IU/l; P < 0.001). The echocardiographic Wall Motion Abnormality Score Index of Group 1 was lower than Group 2 (3.571 vs. 5.589; P < 0.001). Mortality at 35 days in Group 1 was 7.5% vs. 10.7% in Group 2 (-30%; P = n.s.). CONCLUSIONS: The Emergency Room physician, in close collaboration with the cardiologist, supplied a very high standard of pre-Coronary Care Unit diagnosis and therapy. Administration of Anistreplase in the rural Emergency Room brought about a significant reduction of pain to needle time, a significant improvement in left ventricular function and a reduction in mortality.

Aged↗
PubMed1994

Coronary angiographic findings do not predict clinical outcome in patients with unstable angina.

OBJECTIVES: The presence of thrombus formation and type of coronary artery lesion were determined in patients with unstable angina and correlated with the angiographic findings and clinical outcome. BACKGROUND: Some previous studies have suggested that thrombus formation and lesions are predictive of the angiographic and clinical findings. This was evaluated in a retrospective analysis of 159 patients participating in the placebo-controlled Unstable Angina Study Using Eminase (UNASEM) trial on the effect of thrombolysis in unstable angina. METHODS: Patients without a previous myocardial infarction who presented with a typical history of unstable angina in the presence of abnormal findings on the electrocardiogram indicative of ischemia were included in the study. After baseline angiography, study medication (anistreplase or placebo) was given to 126 to 159 patients. Thirty-three patients did not receive medication because of significant main stem disease or normal coronary arteries or for other reasons. Angiography was repeated after 12 to 28 h. RESULTS: Quantitative angiography showed a significant decrease in diameter stenosis in the anistreplase-treated group compared with the placebo-treated group (decrease 11% vs. 3%, p = 0.008). No differences in clinical outcome were found when thrombolytic treatment was compared with placebo (p = 0.98). Neither the presence nor absence of thrombus formation (p = 0.98) nor the type of lesion (p = 0.96) was related to the changes in diameter stenosis or to clinical outcome (p = 0.90 and p = 0.77, respectively). The power of these analyses to detect a 20% difference varied between 56% and 74%. CONCLUSIONS: In this selected group of patients with unstable angina, type of coronary artery lesion and the presence or absence of thrombus formation does not predict clinical outcome.

Aged↗
PubMed1995

Incomplete recanalization as an important determinant of Thrombolysis in Myocardial Infarction (TIMI) grade 2 flow after thrombolytic therapy for acute myocardial infarction. TEAM Investigators. Thrombolytic Trial of Eminase in Acute Myocardial Infarction.

The outcome of patients with Thrombolysis in Myocardial Infarction (TIMI) trial grade 2 flow is worse than that of patients with TIMI grade 3 flow after thrombolytic therapy for acute myocardial infarction. It is unclear whether TIMI grade 2 flow represents incomplete recanalization of the culprit lesion or poor distal runoff. The Thrombolytic Trial of Eminase (anistreplase) in Acute Myocardial Infarction (TEAM)-2 and TEAM-3 were randomized trials comparing anistreplase with streptokinase (TEAM-2, n = 370) or with alteplase (tissue plasminogen activator) (TEAM-3, n = 325). We compared the minimal luminal diameter of the culprit lesion in patients with TIMI grade 2 flow with that in patients with TIMI grade 3 flow both 90 minutes (TEAM-2) and 1 day (TEAM-3) after thrombolysis. Patients with TIMI grade 2 flow had a lower residual luminal diameter in the culprit lesion than patients with TIMI grade 3 flow (TEAM-2, 0.58 +/- 0.03 vs 0.79 +/- 0.02 mm, p = 0.0001; TEAM-3, 0.88 +/- 0.04 vs 1.17 +/- 0.03 mm, p = 0.0001, for patients with TIMI grades 2 and 3 flow). Residual percent stenosis was correspondingly higher in patients with TIMI grade 2 flow. At the early angiogram, 66% of patients with TIMI grade 2 flow, but only 35% of those with TIMI grade 3 flow, had a minimal luminal diameter of 0.6 mm (positive predictive value 87%, negative predictive value 35%). Incomplete recanalization of the culprit lesion may thus be an important determinant of TIMI grade 2 flow after thrombolysis. Whether more complete thrombolysis or rescue angioplasty improves outcome in these patients deserves evaluation.

Analysis of Variance↗
PubMed1993

Prehospital thrombolytic therapy in patients with suspected acute myocardial infarction.

BACKGROUND: The efficacy of thrombolytic therapy for acute myocardial infarction depends partly on how soon after the onset of symptoms it is administered. We therefore studied the efficacy and safety of thrombolytic therapy administered before hospital admission and thrombolytic therapy administered after admission in patients with suspected myocardial infarction. METHODS: In a multicenter, double-blind study, patients seen within six hours of the onset of symptoms who had a qualifying 12-lead electrocardiogram were randomly assigned to receive either anistreplase before admission, followed by placebo in the hospital (prehospital group), or placebo before admission, followed by anistreplase in the hospital (hospital group). Prehospital therapy was administered by emergency medical personnel. RESULTS: A total of 2750 patients were randomly assigned to the prehospital group, and 2719 to the hospital group. The patients in the prehospital group received thrombolytic therapy a median of 55 minutes earlier than those in the hospital group. We observed a nonsignificant reduction in overall mortality at 30 days in the prehospital group (9.7 percent vs. 11.1 percent in the hospital group; reduction in risk, 13 percent; 95 percent confidence interval, -1 to 26 percent; P = 0.08). Death from cardiac causes was significantly less frequent in the prehospital group than in the hospital group (8.3 percent vs. 9.8 percent; reduction in risk, 16 percent; 95 percent confidence interval, 0 to 29 percent; P = 0.049). Particular adverse events occurred more frequently in the prehospital group during the period before hospitalization; among these events were ventricular fibrillation (P = 0.02), shock (P < 0.001), symptomatic hypotension (P < 0.001), and symptomatic bradycardia (P = 0.001). With the exception of symptomatic hypotension, however, the overall incidence of these events was similar for both groups. CONCLUSIONS: Prehospital thrombolytic therapy for patients with suspected myocardial infarction is both feasible and safe when administered by well-equipped, well-trained mobile emergency medical staff. Although such therapy appears to reduce mortality from cardiac causes, our data do not definitely establish that it reduces overall mortality.

Aged↗
PubMed1996

Thrombolytic therapy in Europe: current status.

Thrombolytic therapy is a practical, effective approach to the management of acute myocardial infarction that is widely used in Europe today. Early European trials demonstrated a clear reduction in mortality in patients who received thrombolytic therapy compared with those given conventional treatment. The findings of experimental studies suggest that early reperfusion of the infarct-related artery reduces myocardial damage, which results in the preservation of left ventricular function and, in turn, may improve survival. Although tissue plasminogen activator (t-PA) has been shown to produce more rapid and complete reperfusion than streptokinase, two large-scale clinical trials in which t-PA was given as a standard 3- or 4-h infusion provided no evidence of a survival advantage with this agent. However, the accelerated t-PA regimen used in the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO) study was associated with a lower mortality than streptokinase or a combination of t-PA and streptokinase, thus lending support to the 'open artery' theory. Two recent studies conducted in Europe, the Grampian Region Early Anistreplase Trial (GREAT) and the European Myocardial Infarction Project (EMIP), have demonstrated the feasibility, safety, and efficacy of early thrombolytic therapy before admission to hospital. In GREAT, anistreplase (APSAC) was administered at home by general practitioners. In EMIP, this same agent was given by emergency medical personnel. In both studies, pre-hospital administration reduced the time between the onset of symptoms and initiation of thrombolysis and was associated with a lower mortality rate. Recent data from the European Cooperative Group Study show that the benefits of thrombolytic therapy are maintained for up to 5 years. Research continues in an effort to develop safer and more effective thrombolytic agents. Educational efforts to familiarize the public with the symptoms of myocardial infarction and the development of more rapid, efficient emergency response systems may also improve the outcome of thrombolytic therapy by shortening the time between symptom onset and thrombolytic drug administration.

Anistreplase↗
PubMed1996

Ventricular fibrillation following administration of thrombolytic treatment. The EMIP experience. European Myocardial Infarction Project.

Reperfusion-induced ventricular fibrillation has been demonstrated in animal models of myocardial ischaemia, but no evidence exists for this in humans. The European Myocardial Infarction Project compared the efficacy and safety of pre-hospital thrombolytic therapy with that of hospital therapy. The objective of this study was to investigate the occurrence of reperfusion-induced ventricular fibrillation in acute myocardial infarction patients following thrombolytic therapy. In a double-blind multicentre trial, eligible patients were randomized to receive anistreplase at home followed by placebo in the hospital (A/P group), or placebo followed by anistreplase (P/A group). The occurrence of ventricular fibrillation, and other adverse events were recorded on specific study forms and could be attributed to defined time intervals. The incidence of ventricular fibrillation in the A/P group was significantly higher following the pre-hospital injection than in the P/A group (2.5% vs 1.6%; P = 0.021); the situation was reversed following the hospital injection (3.6% vs 5.3%; P = 0.002). No relationship was found between this excess of ventricular fibrillation and the patients' condition, with the exception of the site of the infarct. These results suggest the existence of reperfusion-induced ventricular fibrillation in patients developing myocardial infarction who receive thrombolytic treatment.

Anistreplase↗
PubMed1993

Earliest electrocardiographic evidence of myocardial infarction: implications for thrombolytic treatment. The GREAT Group.

OBJECTIVES: To determine the incidence of the earliest electrocardiographic changes in patients with suspected myocardial infarction and their sensitivity and specificity for predicting the final diagnosis of acute myocardial infarction. DESIGN: Retrospective study of paired electrocardiograms recorded at home and on admission to hospital. SETTING: 29 rural practices in Grampian and teaching hospitals in Aberdeen. PATIENTS: 137 patients participating in the early anistreplase trial in the Grampian region, who received placebo at home and for whom paired electrocardiograms were available. MAIN OUTCOME MEASURES: Classified electrocardiographic abnormalities and diagnosis at discharge. RESULTS: Electrocardiograms were recorded immediately before injection of placebo at home and anistreplase in hospital at median times of 110 and 240 minutes after the onset of symptoms. Definite or probable myocardial infarction was later confirmed in 93 (68%) patients. Of these, 66 (71%) had the same findings on both electrocardiograms of either ST elevation, bundle branch block, or a non-specific abnormality, while 27 (29%) showed a major change of classification between home and hospital recordings; 21 (23%) had ST elevation or bundle branch block on only one of the paired recordings. Although ST elevation was the commonest abnormality in the 93 patients with myocardial infarction, in only 51 was it recorded at home (sensitivity 55%) and in 49 on admission (sensitivity 53%). Of 57 patients with ST elevation at home, six did not have infarction (specificity 86%), while of 51 with ST elevation on admission, two did not have infarction (specificity 95%). CONCLUSIONS: Elevation of the ST segment is a transient electrocardiographic abnormality that has high specificity but low sensitivity for predicting the diagnosis of acute myocardial infarction; it is an unsatisfactory precondition for giving thrombolytic treatment to patients with suspected acute myocardial infarction.

Anistreplase↗
PubMed1996

A comparison of aspirin and anticoagulation following thrombolysis for myocardial infarction (the AFTER study): a multicentre unblinded randomised clinical trial.

OBJECTIVE: To compare aspirin with anticoagulation with regard to risk of cardiac death and reinfarction in patients who received anistreplase thrombolysis for myocardial infarction. DESIGN: A multicentre unblinded randomised clinical trial. SETTING: 38 hospitals in six countries. SUBJECTS: 1036 patients who had been treated with anistreplase for myocardial infarction were randomly assigned to either aspirin (150 mg daily) or anticoagulation (intravenous heparin followed by warfarin or other oral anticoagulant). The trial was stopped earlier than originally intended because of the slowing rate of recruitment. MAIN OUTCOME MEASURE: Cardiac death or recurrent myocardial infarction at 30 days. RESULTS: After 30 days cardiac death or reinfarction, occurred in 11.0% (57/517) of the patients treated with anticoagulation and 11.2% (58/519) of the patients treated with aspirin (odds ratio 1.02, 95% confidence interval 0.69 to 1.50, P = 0.92). Corresponding findings at three months were 13.2% (68/517) and 12.1% (63/519) (0.91, 0.63 to 1.32, P = 0.67). Patients receiving anticoagulation were more likely than patients receiving aspirin to have had severe bleeding or a stroke by three months (3.9% v 1.7% (0.44, 0.20 to 0.97, P = 0.04)). CONCLUSION: No evidence of a difference in the incidence of cardiac events was found between the two treatment groups, though the trial is too small to claim treatment equivalence confidently. A higher incidence of severe bleeding events and strokes was detected in the group receiving anticoagulation, suggesting that aspirin may be the drug of choice for most patients in this context.

Anistreplase↗
PubMed1991

Medical audit and formulary management: a policy for rational use of thrombolytic drugs.

In this article we report on the development, introduction, and maintenance of a policy to promote rational use of thrombolytic drugs by hospital doctors. The work was undertaken within the framework of the voluntarily operated Riverside East drugs guide (formulary) management system (FMS). The policy was introduced in October 1988 and revised in November 1989 to coincide with the launch of the new, expensive thrombolytic drugs, alteplase (rt-PA, Actilyse) in 1988 and antistreplase (APSAC, Eminase) in 1989. Streptokinase was recommended as the first-line drug for patients who had not received it within the last 6 months. The policy was communicated to all staff in meetings and a drugs guide bulletin and reinforced by ward pharmacists. Results over a 15 month period show voluntary compliance by prescribers with the recommended policy. One hundred and seventy-four patients (22% cardiac admissions) presented with acute myocardial infarction. Of these 43 (25%) received streptokinase, the first-line recommended drug, 7 received alteplase and none received anistreplase. The savings in drug expenditure from using streptokinase rather than alteplase or anistreplase for the 15-month period of investigation were over pounds 27,000. This work represents an example of the effectiveness of the Riverside East FMS model in influencing prescribing behaviour.

Anistreplase↗
PubMed2000

Supervision of thrombolysis of acute myocardial infarction using telemedicine.

The treatment of acute myocardial infarction (MI) constitutes a significant problem in remote geographical areas of Greece. Furthermore, thrombolysis, the treatment of choice in the early phase of acute MI, requires the supervision of an expert. We have used thrombolytic treatment, using telemedicine, in remote medical centres. The Onassis Cardiac Surgery Centre was linked to six remote Aegean islands via telemedicine systems which permitted the transmission of 12-lead electrocardiograms (ECGs). The thrombolytic agent anistreplase was administered to patients with acute MI. Supervision, including consultation for treatment of complications, was achieved using the telemedicine system. One hundred and fifty-two ECGs were transmitted during 24 months, of which 108 (71%) indicated specific treatment of a cardiac condition. Ten cases were diagnosed as having acute MI and eight of these were treated with anistreplase. All patients survived acute MI and complications were treated locally. The application of thrombolytic treatment in acute MI is feasible in remote areas, with the use of a telemedicine system.

Acute Disease↗
PubMed1995

Changes in wall motion in patients treated for unstable angina. A suggestion of the stunned and hibernating myocardium in humans. UNASEM Collaborative Study Group. Unstable Angina Study Using Eminase.

BACKGROUND: A double-blind, placebo-controlled study using anistreplase was performed in 159 patients with unstable angina. All patients had a history of unstable angina combined with typical ECG changes and without evidence of a previous, recent, or ongoing myocardial infarction. The purpose of the present study was to analyze the relationship between the patency of the culprit artery and the behavior of the ischemia-related regional left ventricular (LV) wall motion. METHODS AND RESULTS: On entry to the study, all patients received conventional drug therapy: i.v. nitroglycerin therapy, an oral beta-blocking agent, and a calcium antagonist. Baseline angiography was carried out within 3 h after randomization, a mean of 4.2 +/- 3.0 h (range, 1 to 17 h) after the last attack of chest pain. Treatment with trial medication was withheld in 33 cases. Sixty-five patients with coronary artery disease received anistreplase (30 U/5 min)/heparin and 61 patients heparin-only therapy. Angiography was repeated 20.6 +/- 4.6 h (mean +/- SD; range, 12 to 39 h) after the baseline angiographic study. To assess changes in regional myocardial wall motion, the LV wall was divided into seven segments. The ischemia-related coronary artery stenosis was calculated quantitatively and related to the quantitatively assessed mean regional left ventricular ejection fraction (RLVEF) of the ischemia-related segments. In 118 of 126 patients who received trial medication, we found that anistreplase/heparin therapy leads to a significantly (p < 0.01) greater reduction in coronary artery diameter stenosis than heparin-only therapy (n = 63, mean +/- SD, 11 +/- 22, vs n = 55, mean +/- SD, 3 +/- 11%). Anistreplase/heparin therapy was related to a larger significant improvement of the ischemia-related RLVEF than heparin-only therapy, although the latter association was not statistically significant (n = 63, mean +/- SD, 7 +/- 15, vs n = 55, mean +/- SD, 5 +/- 14%). The effects of change of coronary artery stenosis on regional LV wall motion were also determined. A paradoxical finding was that a persistently occluded vessel or a vessel showing an increase in coronary artery stenosis was associated with a greater improvement of the ischemia-related RLVEF than a reopened vessel or a vessel with a reduction in coronary artery stenosis (n = 15, mean +/- SD, 7 +/- 11, vs n = 41, mean +/- SD, 8 +/- 13, vs n = 15, mean +/- SD, 1 +/- 12, vs n = 47, mean +/- SD, 5 +/- 16%, NS). One day after the last attack of chest pain, the regional LV wall motion was still abnormal in about 20% of patients. CONCLUSION: In these patients with unstable angina, the LV wall motion improved both in the treated and the control group at follow-up angiography 1 day later. Improved coronary arterial anatomy was associated with a lesser improvement of the LV contractile function than when worsening of the coronary angiographic appearance occurred. There is no rational explanation of these results. This is a beginning of an effort to elucidate the clinical significance of the stunned and hibernating myocardium in humans.

Aged↗
PubMed1992

Thrombolytic therapy in acute myocardial infarction.

Multiple clinical trials have demonstrated that thrombolytic treatment early in the course of acute myocardial infarction significantly reduces mortality. Patients under 75 years of age who have had chest pain for no longer than six hours and who demonstrate ST-segment elevation on electrocardiogram are the best candidates for this therapy. Recent studies suggest that there is little difference in effectiveness among streptokinase, alteplase and anistreplase. However, streptokinase is 10 times less expensive than the other agents and causes fewer intracranial bleeds, the major serious adverse effect of thrombolytic therapy. An advantage of anistreplase is that it can be given in a five-minute bolus injection, compared with a one-hour infusion for streptokinase and a three-hour infusion for alteplase. Thrombolytic therapy is contraindicated in patients with known pregnancy, active internal bleeding, uncontrolled hypertension, aortic dissection, intracranial neoplasm or a history of hemorrhagic stroke. Heparin should be administered with both alteplase and streptokinase. Aspirin, beta blockers, nitrates and lidocaine are useful adjunctive therapies in the setting of an acute myocardial infarction.

Angioplasty, Balloon, Coronary↗
PubMed1991

The cost-effectiveness of thrombolytic therapy following acute myocardial infarction.

The increasing use of thrombolytic therapy following acute myocardial infarction has given rise to value for money questions. This study examines the cost-effectiveness of the thrombolytic agent anistreplase (Eminase). Using clinical trial data on the efficacy of anistreplase compared to placebo, and retrospectively obtained cost data from the National Health Service, the study estimates the cost per life-year saved of using this therapeutic agent. The results suggest that the cost-effectiveness of thrombolytic therapy compares favourably with that of other forms of coronary disease treatment. The study concludes that comparisons of the relative cost-effectiveness of different thrombolytic agents are an obvious next step, once full results from recent clinical trials are available.

Aged↗
PubMed1991

Comparative analysis of long-term mortality after thrombolytic therapy.

In patients with acute myocardial infarction, thrombolytic therapy has a demonstrable and favorable impact on a range of clinical indicators, including left ventricular function, infarct size, coronary arterial patency, and symptom relief. However, these indicators have not provided a reliable basis for the comparison of thrombolytic regimens; mortality provides the "gold standard." One-year mortality obviates the differences in the timing of short-term comparisons (in-hospital, 30-day, or 5-week). In addition, late effects of differences in patency, including the impact of reocclusion, infarct healing, and remodeling, will be evident by 1 year. Meta-analysis of data from previous major mortality studies shows that differences in design and the overlap of confidence intervals of mortality studies suggest that no thrombolytic agent is superior in terms of short-term mortality. Long-term survival may provide a more meaningful basis for comparison of efficacy of the thrombolytic regimens. Long-term mortality has been evaluated for anistreplase in acute myocardial infarction in a composite analysis, similar to a meta-analysis. From the pooled life table analysis of all anistreplase studies, the odds reduction in mortality at 1 year was approximately 48%.

Fibrinolytic Agents↗
PubMed1995

Does the potential for development of streptokinase antibodies change the risk-benefit ratio in older patients?

In patients with acute myocardial infarction (MI), quick initiation of thrombolytic therapy is the best strategy for improvement of survival and reduction of morbidity. Streptokinase, a purified product of haemolytic streptococci, is the most commonly administered agent. The compound anistreplase (a complex of streptokinase to plasminogen), is available but currently not often used. The non-antigenic competitor for these two compounds for the indication of MI is alteplase (recombinant tissue plasminogen activator, rt-PA). Due to former use of streptokinase or its derivative anistreplase, patients may develop specific antibodies to the foreign protein, whereas cross-reacting antibodies may be due to streptococcal infections. These antibodies may neutralise streptokinase or its derivative in case of (re)administration and may mediate adverse events, sometimes serious. Since advanced age by itself is certainly not a contraindication to thrombolytic therapy, and because reinfarction occurs frequently, the benefit-risk ratio of re-exposure to streptokinase or its derivative is decreased in the elderly who present with reinfarction. In the framework of tailored thrombolytic therapy, alteplase or urokinase appear to be the drugs of choice in these patients.

Aged↗
PubMed1996

Streptokinase. A pharmacoeconomic appraisal of its use in the management of acute myocardial infarction.

Thrombolytic therapy with streptokinase and other agents reduces mortality and is now well accepted as the mainstay of revascularisation options for most patients after an acute myocardial infarction. Streptokinase is as efficacious as alteplase (recombinant tissue plasminogen activator; rt-PA) when given as a 3-hour infusion, anistreplase, reteplase and saruplase in reducing mortality. However, in the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO) trial, an accelerated alteplase regimen (1.5-hour infusion) plus intravenous heparin demonstrated a statistically significant 1% absolute mortality reduction compared with streptokinase plus heparin. Treatment with streptokinase is consistently clinically superior to conventional treatment and is cost effective: the marginal cost per year of life saved (cost/YLS) is less than $US/$Can20,000 (1990 or 1991 currency) assuming 5-year survival. In addition, streptokinase treatment is associated with fewer intensive care days and total days spent in hospital and a decrease in the use of intensive care services compared with conventional therapy. Importantly, the cost/YLS of treating older patients (70 to 80 years) with streptokinase is similar to that in younger patients (approximately $US22,000, 1990 currency). In 1 study, the cost of in-hospital treatment and associated 1-year follow-up costs did not differ significantly regardless of whether patients received streptokinase or anistreplase. In the most comprehensive cost-effectiveness analysis to date, GUSTO investigators determined that the incremental cost/YLS in patients who received the accelerated alteplase regimen instead of streptokinase was $US32,678 (1993 currency); the projected life expectancy was about 15 years. Thrombolytic therapy is generally more cost effective in patients at high risk than in those at low risk. The cost effectiveness of streptokinase is dependent on infarct location and time to treatment, but is more favorable in patients with anterior than inferior infarctions and those treated as soon as possible after symptom onset. There are as yet no comparative data to indicate a clinical benefit for one thrombolytic agent over another in patients treated more than 6 hours after symptom onset; therefore, in all likelihood, streptokinase will be preferred on the basis of cost minimisation. Streptokinase is associated with a slightly higher rate of severe bleeding than alteplase but a lower incidence of stroke. Although quality-of-life information comparing thrombolytics is unavailable, most patients who received streptokinase or alteplase rated their quality of life as high on the basis of results from time trade-off assessments and health surveys. In summary, streptokinase is undeniably cost effective compared with conventional treatment. It is up to individual healthcare systems to determine whether the mortality advantage and cost differential of the accelerated alteplase regimen over streptokinase, as seen in the GUSTO trial, are affordable and justifiable. However, it is important to realise that treatment options may be limited by healthcare resources; thus, streptokinase can be regarded as a cost-effective thrombolytic strategy which is both efficacious and affordable within the constraints of most healthcare budgets.

Aged↗
PubMed1994

[t-PA in thrombolytic therapy of acute myocardial infarct].

In the past decade, thrombolytic therapy has become standard treatment of acute myocardial infarction. When the importance of thrombosis in the pathogenesis of acute infarction was fully recognised, several plasminogen activators were developed, streptokinase, urokinase, recombinant tissue-type plasminogen activator (t-PA, alteplase), anistreplase and saruplase (prourokinase). Thrombolytic agents are plasminogen activators which possess as a common characteristic the ability to activate plasminogen to plasmin, and result in fibrinolysis and varying degrees of depletion of circulating fibrinogen, factor V and factor VIII. A lot of animal experiments provided the basis for the rationale that recanalisation and reperfusion early in the course of myocardial infarction would limit myocardial necrosis, improve left ventricular function, and improve patient outcome. Native tissue plasminogen activator is normally secreted by vascular endothelium and the most important property of the drug is its relative fibrin specificity. Fibrin strikingly increases the rate of conversion of plasminogen to plasmin by t-PA. The isolation of the complementary DNA coding for t-PA, its insertion into the genome of Chinese hamster ovary cells, and its expression in suspension cultures of these cells have facilitated the large-scale production of t-PA, making it available as a drug for the treatment of acute myocardial infarction. A variety of dosage schemes have been used for alteplase, the standard schedule has been 100 mg given over 3 hours. Higher doses and faster administration (accelerated, front-loaded) are associated with higher patency rates. Alteplase has generally but not always been shown to have higher reocclusion rates than the non-fibrin-specific plasminogen activators. Reocclusion has been shown to be associated with adverse clinical outcome. Therefore, the rate of reocclusion is considered an important measure in evaluating thrombolytic regimens. The combination of alteplase with either urokinase or streptokinase has resulted in early patency rates comparable to alteplase alone, and low rates of reocclusion. Large, randomised clinical trials have demonstrated that thrombolytic therapy reduces mortality significantly in patients with ST elevation treated within the first 6 to 12 hours of acute myocardial infarction. As compared to an overall reduction of mortality with thrombolytic treatment, neither the GISSI-2/international trial nor the Third International Study of Infarct Survival (ISIS-3) trial of more than 60,000 patients found a difference in associated mortality between the use of streptokinase and the use of t-PA, or between the use of these agents and that of anistreplase. The addition of subcutaneous heparin to the regimens did not significantly reduce mortality as compared with no use of heparin.(ABSTRACT TRUNCATED AT 400 WORDS)

Dose-Response Relationship, Drug↗
PubMed1996

Thrombolytic agents--an overview.

Thrombolysis today has become a routine option not only in the treatment of acute myocardial infarction but also in many other manifestations of thromboembolic disease. Until one decade ago, only two plasminogen activators, streptokinase and urokinase, were available for clinical use. They were characterized by limited thrombolytic potencies and major side effects including systemic fibrinogen breakdown, bleeds and stroke. This has prompted the search for new plasminogen activators with better pharmacological and clinical profiles. The first such new plasminogen activators were Anistreplase, a chemically modified version of the streptokinase-plasminogen-activator-complex and tissue-type plasminogen-activator produced by recombinant technology. Both new substances have fueled the development in modern thrombolytic treatment. While the clinical progress with t-PA was confirmed in large, double-blind, randomized, multicenter trials, no real superiority of anistreplase over the traditional plasminogen activators urokinase and streptokinase has been substantiated. While the clinical use of t-PA today has been established for acute myocardial infarction, pulmonary embolism and deep vein thrombosis, current research is focused on further plasminogen activators with further improved thrombolytic properties. This review summarizes the current knowledge on the biochemical and pharmacological properties of the first, second and future generation of plasminogen activators.

Fibrinolytic Agents↗