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Interactions between thrombolytic agents and platelets: effects of plasmin on platelet glycoproteins Ib and IIb/IIIa.

The mechanisms by which thrombolytic agents affect platelet function are not yet elucidated. The aim of the present study was to investigate the effects of plasmin, generated by thrombolytic agents in plasma, on platelet glycoproteins (GP) Ib and IIb/IIIa. Platelet-rich plasma was incubated with pharmacological amounts of streptokinase, anistreplase and tissue-type plasminogen activator and the platelet surface GP's were investigated with a panel of monoclonal antibodies using flow cytometry. As assessed from the mean fluorescence intensity of incubated and control platelets, no significant changes in the binding of antibodies to GP Ib and GP IIb/IIIa were found. The functional integrity of these glycoproteins was severely impaired by treatment with the thrombolytic agents, as shown by significant inhibition of ADP- and ristocetin-induced platelet aggregation. Experiments with purified plasmin and washed platelets indicated significant degradation of GP IIb/IIIa and upregulation of GP Ib, which is in agreement with previous findings. In addition, platelet activation by plasmin was shown using two monoclonal antibodies to activation-specific antigens. We conclude that degradation of platelet GP's by plasmin offers no likely explanation for the defect in platelet function, which is induced by thrombolytic agents in platelet-rich plasma.

Anistreplase↗

Impact of resuscitation and thrombolysis on mortality rate from acute myocardial infarction.

Our objective was to estimate the saving of life by thrombolysis and resuscitation in acute myocardial infarction (AMI) before and after hospital admission. We studied all 1516 patients admitted to a Scottish teaching hospital in 1990 and 1992 who had a final diagnosis of AMI, and 311 patients enrolled in the Grampian region early anistreplase trial (GREAT). Cardiac arrest occurred in 250/1516 (16%) hospital patients. Of these, 77 (31%) were discharged alive--a saving of 51 lives per thousand cases. 797 (53%) patients received thrombolysis, of whom 114 (14%) died. Assuming the same relative reduction in mortality as in the second international study of infarct survival (ISIS-2; 23%), 34 lives were saved by thrombolytic therapy, representing 22 lives per thousand cases. Of 311 patients in GREAT, 15 (5%) had prehospital cardiac arrest, with 7 patients surviving to discharge (48%)--a saving of 23 lives per thousand cases. Those patients given domiciliary thrombolysis had a one month mortality of 6.7% (11/163) compared with 12.2% (18/148) for those receiving hospital thrombolysis--a saving of 55 lives per thousand cases for prehospital thrombolysis. This is additional to 28 lives per thousand estimated for thrombolytic therapy in hospital, totalling 83 lives saved per thousand cases of AMI receiving thrombolytic therapy prehospital. In hospital, more lives were saved by resuscitation than by thrombolytic therapy, but this ratio was reversed in the period before hospital admission. These results emphasise the paramount importance of resuscitation in hospital, and the enhanced efficacy of thrombolysis when given at the earliest opportunity.

Aged↗

Thrombolysis: the need for a critical review.

The (Thrombolysis in Myocardial Infarction) TIMI-I trial led to the hypothesis that the greater reperfusion rate seen with recombinant tissue-type plasminogen activator (rt-PA) versus streptokinase would result in greater reductions in infarct size and mortality in patients with acute myocardial infarction. Despite extensive investigation, no trial comparing rt-PA with streptokinase (European Cooperative Study Group, Plasminogen Activator Italian Multicenter Study [PAIMS], Gruppo Italiano per lo Studio della Sopravvivenze nell'Infarto Miocardico [GISSI-2], International Study on Infarct Survival [ISIS-3], even TIMI-I itself) nor rt-PA and anisoylated plasminogen-streptokinase activator complex (APSAC or anistreplase) (Bassand, TEAM-3, ISIS-3), have confirmed this hypothesis. In a reversal of traditional scientific method, the studies, rather than the unconfirmed hypothesis, have been rejected. A lack of independent review of this subject may have contributed to this outcome. It is proposed that standards of review and editorial comment mandating true critical distance and independence be followed, permitting greater independence of scientific inquiry, review and debate.

Anistreplase↗

Does thrombolysis in myocardial infarction (TIMI) perfusion grade 2 represent a mostly patent artery or a mostly occluded artery? Enzymatic and electrocardiographic evidence from the TEAM-2 study. Second Multicenter Thrombolysis Trial of Eminase in Acute Myocardial Infarction.

One measure of the success of thrombolysis is the early patency status of the infarct-related coronary artery. The Thrombolysis in Myocardial Infarction (TIMI) study group designated patency grades 0 (occluded) or 1 (minimal perfusion) as thrombolysis failure and grade 2 (partial perfusion) or 3 (complete perfusion) as success. To evaluate their true functional significance, perfusion grades were compared with enzymatic and electrocardiographic (ECG) indexes of myocardial infarction in 359 patients treated within 4 h with anistreplase (APSAC) or streptokinase. Serum enzymes and ECGs were assessed serially. Patency was determined at 90 to 240 min (median 2.1 h) and graded by an observer who had no knowledge of patient data. Results for the two drug arms were similar and combined. Distribution of patency was grade 0 = 20%, n = 72; grade 1 = 8% n = 27; grade 2 = 16%, n = 58 and grade 3 = 56%, n = 202. Interventions were performed after angiography but within 24 h in 51% (n = 37), 70% (n = 19), 41% (n = 24) and 14% (n = 28) of patients with grades 0, 1, 2 and 3, respectively. Outcomes were compared among the four patency groups by the orthogonal contrast method. Patients with perfusion grade 2 did not differ significantly from those with grade 0 or 1 in enzymatic peaks, time to peak activity and evolution of summed ST segments, Q waves and R waves (contrast 2). Conversely, comparisons of patients with grade 3 perfusion with those with grades 0 to 2 yielded significant differences for enzymatic peaks and time to peak activity for three of the four enzymes (p = 0.02 to 0.0001) and ECG indexes of myocardial infarction (p = 0.02 to 0.0001) (contrast 3). Thus, patients with grade 2 flow have indexes of myocardial infarction similar to those in patients with an occluded artery (grades 0 and 1 flow). Only early grade 3 flow results in a significantly better outcome than that of the other grades. Because early achievement of grade 2 flow does not appear to lead to optimal myocardial salvage, the frequency of achieving grade 3 perfusion alone may best measure the reperfusion success of thrombolytic therapy.

Anistreplase↗

Prehospital thrombolysis: beneficial effects of very early treatment on infarct size and left ventricular function.

OBJECTIVES: The purpose of this study was to compare the effects of very early (< or = 1.5 h after symptom onset) and later (> 1.5 up to 4 h) thrombolytic therapy on infarct size, left ventricular function and early mortality in patients with acute myocardial infarction. To start thrombolysis at the earliest possible moment, it was performed in the prehospital setting. A cutoff time of 1.5 h was prospectively stipulated. BACKGROUND: Shortening of ischemic time is crucial within the 1st 2 h. Prehospital thrombolysis can reduce time to treatment and enables very early initiation of therapy for many patients. METHODS: One hundred seventy patients received 30 mg of anistreplase up to 4 h from symptom onset by a mobile intensive care unit physician. Infarct size was measured from cumulative release of alpha-hydroxybutyrate dehydrogenase, and left ventricular function was assessed by contrast angiograms 10 days after the infarction. RESULTS: The decision to treat on scene was correct in 98% of patients. There were no bleeding complications or deaths outside the hospital setting. In 28 patients (17%) the ischemic process was interrupted. Findings with thrombolytic therapy initiated < or = 1.5 (96 patients) versus > 1.5 h (74 patients) were the following: initial extent of epicardial injury, 1.6 +/- 0.9 versus 1.4 +/- 0.7 mV, p = NS; infarct size by cardiac enzyme release 646 +/- 634 versus 886 +/- 712 IU/liter, p < 0.05; ejection fraction 57 +/- 14% versus 51 +/- 13%, p < 0.05; regional dyssynergic area 24 +/- 22 versus 33 +/- 24 U, p < 0.05; 21-day mortality 1 of 96 versus 5 of 74 patients (1% vs. 7%, p < 0.05). CONCLUSIONS: The data suggest that in evolving myocardial infarction up to 4 h in duration, the start of thrombolytic therapy at < or = 1.5 h compared with > 1.5 h limits infarct size, preserves left ventricular function and may save lives.

Aged↗

Multivariate associates of QT dispersion in patients with acute myocardial infarction: primacy of patency status of the infarct-related artery. TEAM-3 Investigators. Third trial of Thrombolysis with Eminase in Acute Myocardial Infarction.

BACKGROUND: QT dispersion (QTd; QT interval maximum minus minimum) has been shown to reflect regional variations in ventricular repolarization and is increased in patients with life-threatening ventricular arrhythmias. METHODS: To determine correlates of QTd in patients who had had myocardial infarction (MI), 207 patients (158 men, aged 57 +/- 11 years) with acute MI who were treated with alteplase or anistreplase within 2.7 +/- 0.9 hours of symptom onset were studied. Angiograms at a median of 27 hours after thrombolysis showed reperfusion (Thrombolysis in Myocardial Infarction grade > or =2) in 184 (88%) patients. QT was measured in 10 +/- 2 leads on discharge electrocardiograms with a computerized analysis program interfaced with a digitizer. Associations of QTd with 24 variables related to patient characteristics, acute MI, angiography, interventions, and radionuclide ventriculography were evaluated by univariate and multivariate regression. RESULTS: Univariate associations with QTd (p < or = 0.10) were Thrombolysis in Myocardial Infarction flow grade 0/1 versus 2/3 (QTd = 75 +/- 33 msec vs 53 +/- 22 msec, p < 0.0001), minimal luminal diameter (p = 0.007), left ventricular ejection fraction at discharge (p = 0.007), reinfarction (p = 0.01), number of leads with ST elevation (p = 0.05), end-systolic volume at discharge (p = 0.04), time to peak creatine kinase (p = 0.06), and YST elevation (p = 0.10). Independent associates of QTd were Thrombolysis in Myocardial Infarction grade 0/1 versus 2/3 (p < 0.0001), reinfarction (p = 0.005), and ejection fraction (p = 0.02). CONCLUSIONS: Successful thrombolysis is associated with less QTd in patients after acute MI. Our results support the hypothesis that QTd after MI depends on reperfusion status, reinfarction, and left ventricular function. Reduction in QTd may be an additional mechanism by which the benefit of thrombolytic therapy is realized.

Anistreplase↗

Rescue angioplasty in the thrombolysis in myocardial infarction (TIMI) 4 trial.

Rescue percutaneous transluminal coronary angioplasty (PTCA) has been used to establish reperfusion after failed thrombolysis, and the goal of this study was to examine the angiographic and clinical outcomes after rescue PTCA performed for an occluded artery 90 minutes after thrombolysis. Four hundred two patients with acute myocardial infarction were randomized to receive either anistreplase (APSAC), recombinant tissue plasminogen activator, or their combination in the Thrombolysis in Myocardial Infarction (TIMI) 4 trial. The angiographic and clinical outcomes of patients with a patent artery 90 minutes after thrombolysis were compared with those of patients with an occluded artery treated in a nonrandomized fashion with either rescue or no rescue PTCA. At 90 minutes, the number of frames required to opacify standard landmarks (corrected TIMI frame count) was significantly lower (i.e., flow was faster) after successful rescue PTCA (27 +/- 11) than that in patent arteries after successful thrombolysis (39 +/- 20, p < 0.001), and the incidence of TIMI grade 3 flow was correspondingly higher after successful rescue PTCA (87% vs 65%, p = 0.002). In-hospital adverse outcomes (death, recurrent acute myocardial infarction, severe congestive heart failure, cardiogenic shock or an ejection fraction <40%) occurred in 29% of successful rescue PTCAs and in 83% of failed rescue PTCAs (p = 0.01). Among all patients in whom rescue PTCA was performed (successes and failures combined), 35% of patients experienced an adverse outcome, which was the same as the 35% incidence observed in patients not undergoing rescue PTCA (p = NS) and tended to be higher than the 23% incidence observed in patients with patent arteries (p = 0.07). Although successful rescue PTCA for an occluded artery at 90 minutes results in restoration of flow that is superior to that of successful thrombolysis, the incidence of adverse events for the strategy of rescue PTCA as a whole was the same as that of undertaking no PTCA.

Age Factors↗

The incidence and mechanism of hypotension following thrombolytic therapy for acute myocardial infarction with streptokinase-containing agents--lack of relationship to pretreatment streptokinase resistance.

The incidence, amplitude, mechanism and relationship to prior exposure to streptococcal antigen of blood pressure changes to streptokinase-containing thrombolytic agents were investigated in 125 patients treated with either 1.5 x 10(6) IU streptokinase over 60 min or 30 U anistreplase over 5 min, within 6 h of onset of acute myocardial infarction. Twenty-one of 52 patients with anterior and 34 of 73 with inferior myocardial infarction had a hypotensive response. There were no significant differences in the incidence, duration or amplitude of hypotension between the two treatment groups. The maximum mean fall in systolic blood pressure was 16.9 mmHg (95% confidence limits, CL 12.2 to 24.5 mmHg), and the maximum mean fall in diastolic blood pressure was 13.7 mmHg (CL 10.3 to 17.1 mmHg), starting 4 min after start of therapy and resolving within 34 min. Blood pressure changes were well tolerated. Hypotension was not related to pretreatment streptokinase resistance titre, or anti-SK IgG concentration, to changes in plasma fibrinogen, B-beta 15-42 peptide, D-dimer--as indices of thrombin activation and fibrin (-ogen) breakdown--to plasma viscosity. The blood pressure changes following treatment with streptokinase-containing thrombolytic agents in acute myocardial infarction are frequent but well tolerated. The mechanism of hypotension remains unclear, but is not related to prior exposure to streptococcal antigen.

Anistreplase↗

ST-segment analysis: a useful marker for reperfusion after thrombolysis with APSAC? The Belgian EMS Study Group.

The European Multicentre Study (EMS) assessed coronary reperfusion, functional outcome and safety of anistreplase (anisoylated plasminogen streptokinase activator complex = APSAC) compared to a control group treated with heparin alone in patients with a clinical diagnosis of acute myocardial infarction (AMI). In the Belgian subset of data (n = 103) the reperfusion results, based on non-invasive clinical parameters, were significantly better in the APSAC group: 66% versus 18% in the heparin group (P less than 0.0001). No significant difference was found between the two treatment groups with respect to left ventricular function and adverse events. The purpose of the present study was to analyse the indicative value of ST-segment changes as a possible predictor of reperfusion in threatened myocardial tissue. Two scoring systems were used: the first was based on the combined evaluation of three clinical non-invasive parameters (course of chest pain, ECG evaluation of ST segment changes, reperfusion arrhythmias); the second was based on the changes of the sum of the ST-segment (sigma-ST) evaluations on consecutive 12-lead ECGs. There was a good correlation between the combined clinical scoring system and the residual stenosis on coronary angiography (P less than 0.05) and early CK peak (P less than 0.0001). Analysis of the ECG data revealed that a decrease of greater than or equal to 50% of the sum of ST-elevations (sigma-ST) at 2 h post-treatment in both limb and precordial leads is a fairly useful predictor of reperfusion (sensitivity = 73%, specificity = 63%, predictive value = 88%).

Adult↗

Logistical problems in prehospital thrombolysis.

In this study we compared efficacy and safety of prehospital with in-hospital thrombolytic treatment with anistreplase in patients with acute myocardial infarction (AMI). Three-hundred and fifty patients with chest pain were screened for eligibility by the municipal ambulance staff and/or the general practitioner. Patients were included in the absence of contraindications and if the telephone-transmitted ECG showed AMI. In a 6 month period 16 patients (5%) were eligible, but only seven (2%) were randomized. Age over 70 years, duration of chest pain for longer than 4 h and logistic problems were the major factors responsible for the low inclusion rate. The mean time spent at home with and without the ECG procedure was 38 +/- 14 and 14 +/- 8 min, respectively (P less than 0.001). These results demonstrate that in a medium sized town prehospital delivery of intravenous thrombolytic therapy by paramedics and/or the general practitioner is not feasible, leads to unnecessary time delay and may therefore yield no clinical benefits.

Adult↗

Electrocardiographic evidence of myocardial salvage after thrombolysis in acute myocardial infarction.

There is a need for a simple clinical measurement that will indicate the extent of myocardial salvage after successful thrombolysis. This study examined whether coronary artery reperfusion reduced the infarct size as assessed electrocardiographically after thrombolytic treatment. The sum of the (sigma) ST segment area in leads showing ST segment elevation in the 12 lead electrocardiogram at presentation was used as an index of potential myocardial injury (initial ischaemic index). The evolved infarct size at 48 h was assessed by a QRS scoring system. Two groups of patients, both admitted with anterior myocardial infarction within 6 h of onset, were studied. Group 1 (n = 35) received analgesia only and group 2 (n = 33) received thrombolytic treatment either by the intracoronary (streptokinase, n = 13) or intravenous route (anistreplase, n = 20). Reperfusion was assessed angiographically. The mean (SD) potential infarct size assessed by the initial ischaemic index was similar in both groups (group 1, sigma ST area = 115 (60) mm2 and group 2 = 126 (77 mm2). The QRS score representing evolved infarct size was significantly lower in the treated group (4.1 (2.5] than in group 1 (7.8 (2.6]. The 95% confidence intervals for QRS scores based on the admission sigma ST area from patients with successful reperfusion were applied to a third set of patients (n = 22) to test the ability of the admission ST area (myocardial injury) to predict the QRS score accurately. While patients with successful reperfusion had significantly lower QRS scores than those who did not (4.5 (3.1) versus 9.3 (3.4)), the wide confidence intervals caused by inter-individual variability precluded an accurate prediction of the QRS score in an individual from the sigma ST area at time of presentation. There was no difference in infarct size in patients treated early (</= 3 h) (QRS score 4.2(2.8)) or later (3-6 h) (4.1(2.1)). This study provides evidence that sequential electrocardiographic changes are reduced in patients with anterior infarction who achieve reperfusion after thrombolytic treatment and that this benefit is shown with treatment given up to six hours after infarct onset. None the less, the relation between the initial ischaemic index and the evolved QRS score has wide confidence intervals, reflecting inter-individual variability, and does not allow the prediction of a QRS score in an individual patient.

Acute Disease↗

Audit of prehospital thrombolysis by general practitioners in peripheral practices in Grampian.

BACKGROUND: In the Grampian region early anistreplase trial (GREAT), domiciliary thrombolysis by general practitioners was associated with a halving of one year mortality compared with hospital administration. However, after completion of the trial and publication of the results, the use of this treatment by general practitioners declined sharply. OBJECTIVE: To increase the proportion of eligible patients receiving timely thrombolytic treatment from their general practitioners. SETTING: Practices in Grampian located > or = 30 minutes' travelling time from Aberdeen Royal Infirmary, where patients with suspected acute myocardial infarction were referred after being seen by general practitioners. AUDIT STANDARD: A call-to-needle time of 90 minutes, as proposed by the British Heart Foundation (BHF). METHODS: Findings of this audit of pre-hospital management of acute myocardial infarction were periodically fed back to the participating doctors, when practice case reviews were also conducted. RESULTS: Of 414 administrations of thrombolytic treatment, 146 (35%) were given by general practitioners and 268 (65%) were deferred until after hospital admission. Median call-to-needle times were 45 (94% < or = 90) and 145 (7% < or = 90) minutes, respectively. Survival at one year was improved with prehospital compared with hospital thrombolysis (83% v 73%; p < 0.05). The proportion of patients receiving thrombolytic treatment from their general practitioners did not increase during the audit. CONCLUSIONS: In practices > or = 30 minutes from hospital, the BHF audit standard was readily achieved if general practitioners gave thrombolytic treatment, but not otherwise. Knowledge of the benefits of early thrombolysis, and feedback of audit results, did not lead to increased prehospital thrombolytic use. Additional incentives are required if general practitioners are to give thrombolytic treatment.

Aged↗

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

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

Anistreplase↗

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

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

Anistreplase↗

TIMI perfusion grade 3 but not grade 2 results in improved outcome after thrombolysis for myocardial infarction. Ventriculographic, enzymatic, and electrocardiographic evidence from the TEAM-3 Study.

BACKGROUND: Coronary patency has been used as a measure of thrombolysis success after acute myocardial infarction. The Thrombolysis in Myocardial Infarction (TIMI) Study Group perfusion grades have gained wide acceptance, with grades 0 (no distal flow) and 1 perfusion (minimal flow) being designated as thrombolysis failures and grades 2 (partial perfusion) and 3 (complete perfusion) as thrombolysis successes. However, the significance of the individual TIMI grades on clinical outcome has not been adequately assessed. METHODS AND RESULTS: To evaluate the functional significance of TIMI perfusion grades, we compared 1-day coronary patency status with ventriculographic, enzymatic, and ECG indexes of acute myocardial infarction in 298 patients treated with anistreplase or alteplase within 4 hours of myocardial infarction symptom onset. Radionuclide ejection fraction was determined at 1 week and at 1 month. Perfusion grades for the entire study population were distributed as 12% (n = 37) grades 0/1, 13% (n = 40) grade 2, and 74% (n = 221) grade 3. Patency profile did not differ between the two thrombolytic regimens. Further coronary interventions were performed after the 1-day patency determination in 43% of patients (43%, 48%, 42%, respectively, in grades 0/1, 2, and 3 patients). The outcome of grade 2 patients did not differ from grades 0/1 patients in ejection fraction, enzyme peaks, ECG markers, or morbidity index. In contrast, grade 3 patients, compared with grades 0-2 patients, showed 1) a greater global ejection fraction at 1 week (54% versus 49%, p = 0.006) and at 1 month (54% versus 49%, p = 0.01), 2) a greater infarct zone ejection fraction at 1 week (41% versus 33%, p = 0.003) and at 1 month (42% versus 32%, p = 0.003), 3) smaller enzyme peaks, significant for lactate dehydrogenase, and shorter times to enzyme peaks, significant for all four enzymes, 4) a smaller QRS score at discharge and at 1 month, and 5) a trend toward a lower morbidity index. CONCLUSIONS: Grade 3 flow predicts significantly better outcomes than lesser grades of flow and represents an important measure of reperfusion success.

Anistreplase↗

Beyond thrombolysis: other effects of thrombolytic drugs.

OBJECTIVE: To review the effects of plasminogen activators (tissue plasminogen activator, streptokinase, and anistreplase) on fibrinogen and thrombin, platelets, complement, blood rheology, and neutrophils. DATA SOURCES: A MEDLINE search, as well as a review of recent scientific abstracts, was conducted to identify pertinent literature. STUDY SELECTION: Focus was placed on studies conducted in humans. However, many in vitro studies have been performed to fully elucidate the effect of plasminogen activators on different aspects of hemostasis and on the fibrinolytic and immune systems. DATA EXTRACTION: Data from in vitro, human, and animal studies were evaluated. DATA SYNTHESIS: There is a discrepancy between 90-minute patency and mortality in acute myocardial infarction patients treated with thrombolytic drugs. This could be caused, in part, by other hematologic and immunologic effects of thrombolytic drugs. Though the emphasis of clinical trials has been infarct-related artery patency, left ventricular function, and mortality, some studies have evaluated the effect of thrombolytic agents on fibrinogen and thrombin, platelets, blood rheology, complement, and neutrophils. This review discusses the alteration of systemic hematologic and immunologic parameters by thrombolytic drugs and the possible clinical implications of these effects. CONCLUSIONS: Although the interactions between thrombolytic drugs, hemostasis, and the fibrinolytic and immune systems are complex and still not fully understood, it appears that these drugs differ in their effects on these systems. A greater understanding of these properties and their clinical implications may ultimately enhance the care and outcome of acute myocardial infarction patients treated with thrombolytic therapy.

Animals↗

The costs and benefits of community thrombolysis for acute myocardial infarction : a decision-analytic model.

BACKGROUND: There is evidence that the earlier a patient reaches hospital and receives thrombolysis, the better the outcome. The GREAT (Grampian Region Early Anistreplase Trial) directly addressed the issue of early thrombolysis by evaluating, in a randomised controlled trial, the efficacy of thrombolysis in the community compared with that administered in hospital. OBJECTIVE: This paper aimed to model the cost and benefits of community compared with hospital thrombolysis from the UK NHS perspective, using efficacy data from the GREAT. METHODS: A decision-analytic approach was used to model these two alternatives. Resource use and cost estimates were estimated for a single tertiary centre. Estimates of effectiveness in life-years were obtained from the 4-year follow-up for patients recruited to the GREAT, using declining exponential approximation of life expectancy. Costs are in pounds sterling, 2000/1 values. RESULTS: Community thrombolysis had an average life expectancy of 12.48 years and hospital thrombolysis had an average life expectancy of 12.39 years. Costs were 361 pounds sterling for community thrombolysis and 300 pounds sterling for hospital thrombolysis. Community thrombolysis led to an additional 0.09 years of life-expectancy gained compared with hospital thrombolysis at an additional cost of 61 pounds sterling per patient. Therefore, the incremental cost per life-year gained for the community thrombolysis service over the hospital thrombolysis service was 667 pounds sterling. Sensitivity analysis showed that estimates of cost per life-year gained were most sensitive to the estimates of survival. CONCLUSION: This model suggests that, from the UK NHS perspective, implementing community thrombolysis may lead to extra survival but at extra cost over hospital thrombolysis. Although the incremental cost per life-year is modest, judgements still have to be made, however, as to whether the extra benefits estimated are worth the additional resources required. This requires consideration of the local context in which the service may be introduced.

Anistreplase↗

Urgent response telecardiology services and training--collaboration between Onassis Cardiac Surgery Hospital and Aegian Islands' Health Care Centers.

Since 1995, Onassis Cardiac Surgery Center participates in the development of Telecardiology Services in Greece. Existing connections include the islands Skiathos, Naxos, Santorini, Mykonos, Milos, Plomari and Amorgos. First hundred fifty three (153) cases have been already analysed. Eleven of them were acute myocardial infarctions and have been treated by thrombolytic medication (anistreplase). The participation of physicians and nurses was valuable for the success of the program and their further involvement in the new area of Telemedicine. The purpose of the project was to offer high quality cardiac services in remote area patients and to provide specific training in telemedicine issues to health care professionals.

Anistreplase↗