Pre-hospital thrombolytic therapy with either alteplase or streptokinase: Practical applications, complications and long-term results in 529 patients

OBJECTIVE: To assess the practical application, safety and long-term outcomeof pre-hospital thrombolytic intervention with either alteplaseor streptokinase in patients with extensive myocardial infarction. DESIGN: Prospective study. SUBJECTS: Patients with chest pain of more than 30 min duration, presentingwithin 6 h of symptom onset and with electrocardiographic evidenceof extensive evolving myocardial infarction. METHODS: Eligibility of patients was established by the general practitioneror the ambulance nurse using a standardized questionnaire with(contra-) indications for thrombolytic therapy. ComputerizedECG was recorded by ambulance nurses. In the presence of extensiveST segment elevation (sum ST deviation of at least 1.0 m V),eligible patients received either 100 mg alteplase (n=246) or50 mg alteplase in the ambulance followed by 0.75 x 10⁶ IE streptokinasein hospital (n=90), or 1.5 x 10⁶ IE streptokinase intravenously(n=193). MAIN OUTCOME MEASUREMENTS: Death and life-threatening complications (ventricular fibrillation,cardiac arrest) and side effects (hypotension, allergic reactions)during transportation to hospital and in the first 24 h followinghospitalization, and survival up to 5 years follow-up. RESULTS: From 1988–1993, 529 patients received thrombolytic treatmentinitiated pre-hospital. The time gained by pre-hospital administrationof thrombolysis amounted to 50 min. The rate of complicationsduring transportation and during the first 24 h after hospitalizationwas low. Hospital mortality was 2% and 1-year mortality 3%.Cumulative survival at 5 years was 92%. This was superior tothe 84% 5-year survival observed in a matched group of 239 patientswith similar baseline characteristics treated with alteplasein hospital. CONCLUSIONS: Pre-hospital administration of either alteplase or streptokinaseis feasible and safe and results in significant time gain. Thelong-term prognosis is excellent in spite of extensive evolvingmyocardial infarction upon admission.     

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.     

Differential effects of tissue plasminogen activator and streptokinase on infarct size and on rate of enzyme release: influence of early infarct related artery patency: The GUSTO Enzyme Substudy

BACKGROUND: The recent international GUSTO trial of 41 021 patients withacute myocardial infarction demonstrated improved 90-mm infarctrelated artery patency as well as reduced mortality in patientstreated with an accelerated regimen of tissue plasminogen activator,compared to patients treated with streptokinase. A regimen combiningtissue plasminogen activator and streptokinase yielded intermediateresults. The present study investigated the effects of treatmenton infarct size and enzyme release kinetics in a subgroup ofthese patients. METHODS: A total of 553 patients from 15 hospitals were enrolled in thestudy. Four thrombolytic strategies were compared: streptokinasewith subcutaneous heparin, streptokinase with intravenous (iv.)heparin, tissue plasminogen activator with iv. heparin, andstreptokinase plus tissue plasminogen activator with i.v. heparin.The activity of alpha-hydroxybutyrate dehydrogenase (HBDH) inplasma was centrally analysed and infarct size was defined ascumulative HBDH release per litre of plasma within 72 h of thefirst symptoms (Q(72)). Patency of the infarct-related vesselwas determined by angiography in 159 patients, 90 mm after treatment. RESULTS: Infarct size was 3·72 g-eq . 1^–1 in patients withadequate coronary perfusion (TIMI-3) at the 90 mm angi-ogramand larger in patients with TIMI-2 (4·35 g-eq . 1^–1)or TIMI 0–1 (5·07 g-eq . 1^–1)flow (P=0·024).In this subset of the GUSTO angiographic study, early coronarypatency rates (TIMI 2+3) were similar in the two streptokinasegroups (53 and 46%). Higher, but similar, patency rates wereobserved in the tissue plasminogen activator and combinationtherapy groups (87 and 90%). Median infarct size for the fourtreatment groups, expressed in gram- equivalents (g-eq) of myocardium,was 4·4, 4·5, 3·9 and 3·9 g-eq perlitre of plasma (P=0·04 for streptokinase vs tissue plasminogenactivator). Six hours after the first symptoms, respectively5·3, 6·6, 14·0 and 13·6% of totalHBDH release was complete (P<0·000l for streptokinasevs tissue plasminogen activator). CONCLUSIONS: Rapid and complete coronary reperfusion salvages myocardialtissue, resulting in limitation of infarct size and acceleratedrelease of proteins from the myocardium. Treatment with tissueplasminogen activator, resulting in earlier reperfusion wasmore effective in reducing infarct size than the streptokinaseregimens, which contributes to the differences in survival betweentreatment groups in the GUSTO trial.     

Pre-hospital and hospital time delays in thrombolytic treatment in patients with suspected acute myocardial infarction: Analysis of data from the EMIP study

OBJECTIVES: To compare the components of the time delay involved in pre-hospitaland hospital thrombolytic therapy in patients presenting withsuspected acute myocardial infarction. MATERIAL AND METHODS: From October 1988 to January 1992 a total of 198 mobile emergencyunits in 15 European countries and Canada randomized 5469 patientsto receive either pre-hospital thrombolytic treatment, followedby placebo in hospital (pre-hospital group), or pre-hospitalplacebo, followed by thrombolytic treatment in hospital (hospitalgroup) in the European Myocardial Infarction Project trial.We performed a post hoc analysis of these data to correlatecomponents of the interval between symptom onset and treatmentwith baseline patient characteristics. RESULTS: The delay between onset of symptoms and calling for an ambulancewas significantly longer for female patients (P0·0001),older patients (>65 years old; P=0·0001), those whohad experienced pain within the previous 24 h (P=0·0001),and those with pulmonary oedema (P=0·04). This delaywas significantly shorter in patients with previous myocardialinfarction (P=0·02), those with ventricular fibrillation(P=0·0001), and those in shock (P0·0001). Thedelay between the two injections was significantly longer forolder patients (>65 years old; P=0·02), those withprevious myocardial infarction (P=0·03), and those inshock (P=0·003). CONCLUSIONS: Action undertaken to reduce delays between symptom onset andtreatment should focus on modifiable factors such as patientswho are likely to be late callers, i.e. women and those over65 years of age.     

Intravenous NPA for the treatment of infarcting myocardium early. InTIME-II, a double-blind comparison of single-bolus lanoteplase vs accelerated alteplase for the treatment of patients with acute myocardial infarction

Aims To compare the efficacy and safety of lanoteplase, a single-bolusthrombolytic drug derived from alteplase tissue plasminogenactivator, with the established accelerated alteplase regimenin patients presenting within 6h of onset of ST elevation acutemyocardial infarction. Methods and Results 15078 patients were recruited from 855 hospitalsworldwide and randomized in a 2:1 ratio to receive either lanoteplase120KU.kg^–1as a single intravenous bolus, or up to 100mgaccelerated alteplase given over 90min. The primary end-pointwas all-cause mortality at 30 days and the hypothesis was thatthe two treatments would be equivalent. By 30 days, 6·61%of alteplase-treated patients and 6·75% lanoteplase-treatedpatients had died (relative risk 1·02). Total strokeoccurred in 1·53% alteplase- and 1·87% lanoteplase-treatedpatients (ns); haemorrhagic stroke rates were 0·64% alteplaseand 1·12% lanoteplase (P=0·004). The net clinicaldeficit of 30-day death or non-fatal disabling stroke was 7·0%and 7·2%, respectively. By 6 months, 8·8% of alteplase-treatedpatients and 8·7% of lanoteplase-treated patients haddied. Conclusion Single-bolus weight-adjusted lanoteplase is an effectivethrombolytic agent, equivalent to alteplase in terms of itsimpact on survival and with a comparable risk-benefit profile.The single-bolus regimen should shorten symptoms to treatmenttimes and be especially convenient for emergency departmentor out-of-hospital administration.     

Late activation of the fibrinolytic system in myocardial infarction treated with thrombolytic therapy: Influence of the coronary anatomical substrate

Procoagulant activity, thrombin and fibrinolytic system activationhave been demonstrated in the first 24–48 h after acutemyocardial infarction treated with thrombolytic therapy. Littleis known about what happens in the subsequent days, during whichthe incidence of ischaemic recurrence is high. In 21 patients treated with streptokinase and in 20 patientstreated with urokinase we evaluated, with multiple plasma determinations,D-dimer and fibrinogen plasma levels in the first week aftermyocardial infarction. From the 2nd hour after the begrnningof thrombolysis to the 4th day, all patients received intravenousheparin in doses sufficient to raise the partial thromboplastintime to twice its normal level; subcutaneous calcium heparin(12 000 U/day) was subsequently substituted for the intravenousroute. Coronary angiography was performed 7 days after infarction.From the basal values 2·22 ± 1·44 nmol.1^–1 in the strep tokinase group and 3·28 ±3·05 nmol . 1^–1 in the urokinase group, D-dimerrose consistently in the 1st hour after thrombolysis 269·4± 206·7 nmol . 1^–1 and 44·5 ±35·5 nmol . 1^–1 in the streptokinase and urokinasegroups, respectively; P<0·00l. After the peak value,which in both groups was reached after 5 h, D-dimer slowly decreasedduring the study period. It reverted to normal values only in10/21 patients in the streptokinase group; in the urokinasegroup normalization was attained in 14/20 patients between the3rd and 6th days. After withdrawal of i.v. heparin in patientsof both groups with TIMI 0 or 1 grade of coronary patency, D-dimerrose to levels four to seven times greater than normal; in patientsof both groups with TIMI 2 or 3 grade coronary flow, D-dimershowed a monophasic pat tern of progressive normalization (P<0·05and P<0·0l at the 6th and 7th days, respectively,for differences between TIMI 0–1 and TIMI 2–3 groups). After myocardial infarction, thrombolysis is followed by activeand persistent fibrin degradation more marked and lasting afterstreptokinase than after urokinase. When occurring sooner, itis a consequence of plasmin activation induced by thrombolyticagents; later it seems to be related to intracoronary substrate,as suggested by the relation ship of plasma elevation of D-dimerwith the presence of occluded or subocciuded infarction-relatedvessels.     

Prehospital thrombolysis with alteplase (rt-PA) in acute myocardial infarction.

The improvement in survival in patients undergoing thrombolytic therapy in myocardial infarction is determined by the delay between coronary occlusion and reperfusion. The REPerfusion in Acute Infarction Rotterdam (REPAIR) study was designed to examine the feasibility and safety of prehospital thrombolysis with alteplase (rt-PA, 'Actilyse'). A small portable ECG computer system is used to confirm the presence of a large myocardial infarction (at least 1.0 mV ST-deviation) 'on the spot'. Between 22 June 1988 and 1 January 1991, 226 patients were treated by the ambulance service after the evaluation of 9052 patients complaining of chest pain. Therapy could be initiated within an average of 100 +/- 56 min (SD) after the onset of symptoms, and within 22 +/- 9 min after ambulance arrival. Three patients were defibrillated during transportation. Six patients (3%) died after arrival in the hospital. The time gained by prehospital treatment was 47 min (95% confidence limits 44-51 min) in comparison with 220 patients who did not meet the criteria for prehospital thrombolysis, but received thrombolytic therapy as soon as possible after hospital admission. The developed procedure allows rapid and safe initiation of thrombolytic therapy in selected patients, even in the absence of a physician. The observed low mortality supports the concept that prehospital thrombolytic therapy is indeed beneficial to the patient.     

The 60 Minutes Myocardial Infarction Project: Treatment and clinical outcome of patients with acute myocardial infarction in Germany

AIMS: To describe patient characteristics, pre-hospital delay, treatment,complications and outcome in patients with acute myocardialinfarction admitted to hospitals in Germany. METHODS AND RESULTS: The study was of prospective observational multicentre design.Those involved were consecutive patients with acute Q-wave myocardialinfarction admitted within 96 h of onset of symptoms to 136German hospitals between July 1992 and September 1994 (n=14980,median age 66 (quartiles 57, 74) years, 68% male, 48% anteriorwall infarction). Median pre-hospital delay was 170 (90, 475)min, with 17% arriving within the first hour and 61% within4 h of onset of symptoms. The following patient groups had ashort pre-hospital delay: males, those aged less than 65 years,those admitted at night or the weekend, those with a previousmyocardial infarction, those in need of cardiopulmonary resuscitation,and those with a diagnostic first ECG. The first ECG was diagnosticin 67·6% of cases. Reperfusion therapy was used in 53%,with thrombolytic therapy in 51·6%. Median time fromadmission to initiation of treatment was 30 (20, 55) min. Respectiverates of treatment with aspirin, nitrates, and beta-blockerswere 81%, 83% and 16%. Major complications were cerebral bleeding(0·4%), bleeding requiring transfusions (0·9%),left ventricular rupture (0·6%) and anaphylactic shock(0·1%). Median hospital stay was 20 (13, 26) days. In-hospitaldeath rate was 17·2%. Increased hospital mortality wasobserved with female gender, an unknown or long pre-hospitaldelay, a diagnostic first ECG, anterior wall infarction, traumaor major operation within the last 14 days, renal insufficiencyand malignoma. CONCLUSIONS: ‘Real-life’ hospital mortality is much higher thanpreviously reported in clinical trials. To reduce hospital mortality,the efficacy of thrombolysis should be increased by shorteningthe pre-hospital delay, and the use of concomitant therapy,especially beta-blockers, should be increased.     

Outcome after thrombolytic therapy of nine cases of myopericarditis misdiagnosed as myocardial infarction

Anecdotal reports have suggested that cardiovascular complicationsmay occur if thrombolytic therapy is performed in cases of pericarditismisdiagnosed as acute myocardial infarction. From 1980 to 1993,47 cases of myopericarditis mimicking myocardial infarctionhave been admitted to our institution. The misdiagnosis wasmade because of clinical onset characterized by a typical chestpain, and/or localized ST segment elevation. Since 1987, nine(919 males, age 40±14 years) out of the 47 patients (19%)have been treated with a thrombolytic agent (streptokinase 419,rt-PA 519) followed by intravenous heparin. This treatment wasstarted during the pre-hospital pliase (2/9) and while in hospital(7/9). No pericardial rub was present; ST segment elevationwas mainly localized in inferior and lateral leads; no Q wavedeveloped; median creatine kinase rise was 268 units (range38 to 1280), and only one patient had a small pericardial effusion.The mean level of fibrinogen after thrombolysis was 1.72 g.l^–1 (range 0.10 to 4.50). In all cases, typical ECG cliangeswere present suggesting pericarditis with a subsequent returnto a normal ECG. No severe cardiac or pericardial complicationor arrhytlxmia occurred; only one patient developed a non-compressiveand resolvable pericardial effusion. Cardiac catheterizations(coronary and left ventricular angiographies) were normal whenperformed (5/9). Long-term follow-up (mean 46±29 months)was favourable without any coronary events. In conclusion, thrombolytictherapy was uncomplicated in our patients with myopericarditissimulating evolving myocardial infarction.     

Beneficial effect of enalapril on left ventricular remodelling in patients with a severe residual stenosis after acute anterior wall infarction

OBJECTIVE: The present study was designed to evaluate the effects of earlyangiotensin converting enzyme (ACE) inhibition on left ventricularenlargement in patients with anterior wall infarction followingreperfusion therapy. METHODS: Seventy-one consecutive patients with an anterior wall myocardialinfarction were randomly allocated to enalapril (n=36) or placebo(n=35). All patients received either thrombolytic therapy (n=46)or underwent primary coronary angioplasty (n=25). Medicationwas started within 48 h admission to hospital and continuedfor 48 weeks. The process of left ventricular remodelling wasassessed with two-dimensional echocardiography at 3 weeks and1 year after the acute onset, and was related to the severityof the residual stenosis of the infarct-related artery. RESULTS: Baseline left ventricular ejection fraction was 39·2±8·7%.During the study period, left ventricular end-diastolic volumeindex increased from 48·2±9·9 ml. m^–2to 54·6±12·2 ml. m^–2 at 3 weeks,and to 59·4±170 ml. m^–2 after 1 year incontrol patients (P<0·001). In the enalapril-treatedpatients, left ventricular end-diastolic volume index increasedfrom 50·0±16·1 to 57·7±19·3ml. m^–2 at 3 weeks, and to 61·9±22·7ml. m^–2 after 1 year (P<0·001). Both at 3 weeksand after 1 year, no overall differences in left ventricularvolumes were observed between the enalapril and the placebogroup (both ns). However, patients with a residual stenosisseverity of 70% in the infarct-related artery (n=43) showedsignificant attenuation of remodelling by enalapril (n=22) whencompared to placebo (n=21). In patients on enalapril, left ventricularend-diastolic volume index increased from 470±130 to53·7±17·7 ml. m^–2 compared to 48·0±9·6to 60·3±16·3 ml . m^–2 in controlpatients (P<0·03). Also diastolic filling parameterswere significantly improved in patients with 70% residual stenosis. CONCLUSION: In patients with an anterior wall infarction and a severe residualinfarct-related coronary artery stenosis following reperfusion,treatment with enalapril prevents the process of left ventricularremodelling. As left ventricular dilatation is an early processwe suggest that treatment with ACE inhibition should be startedas soon as possible in this group of patients.     

Rescue thrombolysis: alteplase as adjuvant treatment after streptokinase in acute myocardial infarction.

BACKGROUND--In acute myocardial infarction patients who do not reperfuse their infarct arteries shortly after thrombolytic treatment have a high morbidity and mortality. Management of this high risk group remains problematic, especially in centres without access to interventional cardiology. Additional thrombolytic treatment may result in reperfusion and improved left ventricular function. METHODS--Failure of reperfusion was assessed non-invasively as less than 25% reduction of ST elevation in the electrocardiographic lead with maximum ST shift on a pretreatment electrocardiogram. 37 patients with acute myocardial infarction who showed electrocardiographic evidence of failed reperfusion 30 minutes after 1.5 MU streptokinase over 60 minutes were randomly allocated to receive either alteplase (tissue type plasminogen activator (rt-PA) 100 mg over three hours) (19 patients) or placebo (18 patients). 43 patients with electrocardiographic evidence of reperfusion after streptokinase acted as controls. Outcome was assessed from the Selvester Q wave score of a predischarge electrocardiogram and a nuclear gated scan for left ventricular ejection fraction 4-6 weeks after discharge. RESULTS--Among patients in whom ST segment elevation was not reduced after streptokinase, alteplase treatment resulted in a significantly smaller electrocardiographic infarct size (14% (8%) v 20% (9%), P = 0.03) and improved left ventricular ejection fraction (44 (10%) v 34% (16%), P = 0.04) compared with placebo. This benefit was confined to patients who failed fibrinogenolysis after streptokinase (fibrinogen > 1 g/l). In patients in whom ST segment elevation was reduced after streptokinase, infarct size and left ventricular ejection fraction were not significantly different from those in patients treated with additional alteplase. CONCLUSION--Patients without electrocardiographic evidence of reperfusion after streptokinase may benefit from further thrombolysis with alteplase.     

Efficacy and Safety of Thrombolysis with Intravenous Streptokinase Initiated Prior to Ambulance Transport from Community Hospital to Tertiary Health Care Center

We studied the safety and efficacy of thrombolytic therapy for acute myocardial infarction initiated prior to ambulance transport. Two treatment regimens were compared in a prospective design: 40 patients (group A) received intravenous streptokinase 5 ± 10⁵ IU (SK-IV) prior to and during ambulance transport and were compared with 36 patients (group B) in whom the same dosage of streptokinase was given after arrival in our hospital. In all patients immediate coronary angiography was performed, followed by intracoronary streptokinase administration. Infarct size was assessed by cumulative release of α-hydroxybutyrate dehydrogenase. Apart from three episodes of ventricular fibrillation no procedure-related complications occurred during transport. Median time to SK-IV was 70 minutes in group A versus 125 minutes in group B (P < 0.001). At first visualization the infarct-related vessel was patent in 23 patients (58%) in group A and in 6 patients (17%) in group B (P < 0.001). Anterior wall infarction median infarct size in group A was 32% smaller than that in group B (P < 0.05). We conclude that SK-IV started before ambulance transport is safe, accelerates early reperfusion rate, and consequently leads to a further limitation of infarct size in patients with anterior wall infarction. (J Interven Cardiol 1989:2:3)     

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.     

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.     

Ambulance despatchers' estimation of intensity of pain and presence of associated symptoms in relation to outcome in patients who call for an ambulance because of acute chest pain

BACKGROUND: A large number of patients who call for an ambulance becauseof acute chest pain have an acute ischaemic event, but somedo not. AIM: To relate the ambulance despatcher's estimated severity of painand presence of associated symptoms, in patients who call foran ambulance because of acute chest pain, to whether they developacute myocardial infarction (AMI) and to the risk of early death. PATIENTS: All those with acute chest pain who contacted the despatch centrein Göteborg over a 2-month period. RESULTS: In all, 503 patients fulfilled the inclusion criteria. Patientsjudged as having severe chest pain (68%) developed AMI duringthe first 3 days in hospital on 26% of occasions as comparedwith 13% among patients judged as having only vague chest pain(P=0·0004). The difference was less marked among theelderly and women. The presence of any of the following associatedsymptoms, dyspnoea, nausea, vertigo, cold sweat or syncope,tended to be associated with a higher infarction rate (24%)than if none of these symptoms was present (1 7%, P=0·06).Mortality during the pre-hospital and the hospital phase wasnot associated with the estimated severity of pain or the presenceof associated symptoms. CONCLUSIONS: The despatcher's estimation of the severity of pain and thepresence of associated symptoms appears to be associated withthe development of AMI but not with early mortality.     

Long-term benefit of early thrombolytic therapy in patients with acute myocardial infarction: 5 year follow-up of a trial conducted by the Interuniversity Cardiology Institute of The Netherlands

Patients (n = 533) who participated in the Interuniversity Cardiology Institute of the Netherlands Trial were followed up for 3 to 7 years. The 5 year survival rate after thrombolytic therapy with intracoronary streptokinase was 81% (269 patients) compared with 71% after conventional therapy (264 patients). The greatest improvement in survival was observed in patients with anterior infarction (81% versus 64% with thrombolytic therapy or conventional therapy, respectively), in those with heart failure on admission or a previous infarction and in those with extensive myocardial ischemia on admission. Left ventricular ejection fraction at the time of hospital discharge was better after thrombolytic therapy. In the hospital survivors, long-term outcome was related to left ventricular function at the time of discharge and, to a lesser extent, to the underlying coronary artery disease. The initial therapy (thrombolysis or conventional) was not an independent additional determinant of long-term survival when left ventricular function and coronary status at the time of hospital discharge were taken into account. Thus, the salutary effects of thrombolytic therapy appear to be the result of myocardial salvage. Reinfarction within 3 years was observed more frequently after thrombolytic therapy, particularly in patients with inferior wall infarction and those with greater than or equal to 90% stenosis of the infarct-related vessel at discharge. Coronary bypass surgery and coronary angioplasty were performed more frequently after thrombolytic therapy than in conventionally treated patients. At 5 years, approximately 40% of patients in both groups had an uneventful course without reinfarction or additional revascularization procedures. These observations demonstrate that the benefits of thrombolytic therapy are maintained throughout 5 years of follow-up.(ABSTRACT TRUNCATED AT 250 WORDS)     

Acute reperfusion strategies for ST-segment elevation myocardial infarction.

The overall aim of reperfusion therapy for patients presentingwith an ST-segment elevation myocardial infarction (STEMI) isto restore normal blood flow in the infarct-related artery asrapidly and completely as possible, and thus myocardial perfusion.This can be achieved by the administration of thrombolytic therapy(either pre-hospital or in hospital) or by primary percutaneouscoronary intervention (PPCI). Guidelines suggest that thrombolytictherapy should be administered within a door to needle time(or medical contact to needle time) of <30 min and a doorto balloon time of <90 min for PPCI.¹ Eagle et al.²     

Pre-hospital diagnosis of myocardial infarction: an opportunity to improve outcomes?

Ortolani et al.¹ report on the potential impact of pre-hospitaldiagnosis of ST-elevation myocardial infarction (STEMI). Theauthors compared the different routes of referral taken by patientswho were transferred for primary percutaneous coronary intervention(PCI). A total of 658 STEMI patients were studied and threepredefined referral routes were compared: pre-hospital diagnosisand direct transportation (for patients within 90 min driveof the PCI centre, n=166), diagnosis at the interventional hospitalemergency department (n=316), or diagnosis at local hospitalsbefore transportation (n=176). The main finding of the studywas that patients who had a pre-hospital paramedic and doctorwith telemedicine transmission of STEMI and direct transferfor primary PCI had a significant reduction in ‘treatmenttime’ (from onset of     

ESPRIT: a European study of the prevention of reocclusion after initial thrombolysis with duteplase in acute myocardial infarction

BACKGROUND: The goal of thrombolytic treatment in acute myocardial infarctionis reperfusion of the infarct-related coronary artery. Duteplaseis a double-chain recombinant tissue-type plasminogen activator.Its efficacy and safety were evaluated in patients with acutemyocardial infarction treated within 4 h of onset of chest painin this multicentre, open, non-controlled trial. METHODS AND RESULTS: A total of 273 patients were enrolled and treated with duteplase0·6 . MU. kg^–1 over 4 h, with concomitant oralaspirin and intravenous heparin. Coronary arteriography wasperformed at 60 min, 90 min and approximately 24 h after thestart of duteplase infusion to assess the perfusion grade (TIMIscoring) of the infarct-related coronary artery. Safety wasassessed by monitoring patients closely for bleeding and forall other adverse experiences during the 72-h study period.Reinfarction during the study period was also recorded, anddeaths at any time during the period in hospital were documented. TIMI: grade 2 or 3 patency of the infarct-related coronary arteryat 90 min was achieved in 70% of the patients and 7% of these‘patent’ infarct-related coronary arteries had reoccludedby 20 to 36 h. Clinical reinfarction during the 72-h study periodwas observed in 7%. Total in-hospital mortality was 8%. Seriousor life-threatening bleeding occurred in 4% of the patients.There was one haemorrhagic stroke, and this was fatal. CONCLUSIONS: Weight-adjusted duteplase infusion, together with oral aspirinand intravenous heparin, in acute myocardial infarction resultedin patency of the infarct-related coronary artery and a safetyprofile comparable to those reported for the other form of tissue-typeplasminogen activator, alteplase, However, there remains a problemwith reocclusion and reinfarction after initially successfulthrombolysis. (Eur Heart J 1996; 17: 1522–1531)     

Reduced occurrence of atrial fibrillation in acute myocardial infarction treated with streptokinase

In a hisiorical follow-up study of 152 hospital patients withacute myocardial infarction, the frequency of life-threateningarrhythmias (ventricular fibrillation, sustained ventriculartachycardia, 3rd degree AV-block, 2nd degree AV-block (Mobitztype II), and asystole) and atrialfibrillation in 76 patientstreated with streptokinase was compared with their frequencyin 76 patients who did not receive a thrombolytic therapy. Among those treated with streptokinase two patients (3%) developedatrial fibrillation, compared with 12 (16%) in the control group(P=0·009 Life-threatening arrhythmias occurred with equalfrequency in the two groups. Further studies should confirmand clar the mechanism of the reduced frequency of a trial fibrillationin the streptokinase-treated patients.