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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.
The primary objective of our 163-center trial, referred to as the European Myocardial Infarction Project (EMIP), was to evaluate the benefits and risks of prehospital thrombolytic therapy, as compared with thrombolytic therapy administered in the hospital, for patients with suspected myocardial infarction who were seen within six hours of the onset of symptoms18.
Methods
We randomly assigned eligible patients to receive either 30 units of anistreplase when they were first seen by emergency medical personnel outside the hospital, followed by placebo after hospital admission (prehospital group), or placebo when first seen outside the hospital, followed by 30 units of anistreplase after hospital admission (hospital group), under double-blind conditions. Anistreplase has a long half-life and can be conveniently administered as an intravenous injection over four to five minutes. Other treatment, both in the ambulance and in the hospital, was given at the discretion of the attending physician.
Data on all patients (whether eligible or ineligible for the study) who had suspected myocardial infarction when they were seen by the staff of mobile emergency units were recorded in a register. Patients with pain characteristic of myocardial infarction and lasting for at least 30 minutes, or pain lasting for less than 30 minutes but still present and not responsive to nitrates, who were seen within 6 hours of the onset of symptoms and who underwent 12-lead electrocardiography (see below) were eligible.
Patients were excluded if they were receiving oral anticoagulant treatment (but aspirin, dipyridamole, or any other antiplatelet drug was allowed); if they were known to have a hemorrhagic diathesis or a recently active peptic ulcer; if they had had a stroke, surgery, or major trauma in the previous six months; if they had undergone external cardiac massage for the present symptoms; if they had a systolic blood pressure above 200 mm Hg or a diastolic blood pressure above 120 mm Hg; if they were known or suspected to be pregnant; if they had had percutaneous transluminal coronary angioplasty in the previous two weeks; or if they declined to give their consent to participate. They could also be excluded for any other reason at the discretion of the investigator.
Randomization was stratified according to whether or not ST-segment elevation was present on the electrocardiogram. Patients were randomly assigned within the "elevated ST segment" stratum if the electrocardiogram was suggestive of evolving myocardial infarction -- that is, if there was ST-segment elevation of at least 1 mm in two limb leads, elevation of at least 2 mm in at least two precordial leads, or both. Patients with atypical electrocardiograms (i.e., QRS duration of >0.12 second, isolated ST-segment depression, tall T waves, or other abnormalities) associated with a history of coronary atherosclerotic disease such as angina pectoris or previous myocardial infarction were randomly assigned within the "no elevated ST segment" stratum. Randomization was also stratified according to center.
After assessment of the patient's eligibility, treatment was assigned with use of a pocket microcomputer (PSION Organiser II). The first injection, either anistreplase or placebo, was administered before the patient's transfer to the hospital, and on his or her arrival at the hospital the box containing the treatment was given to the hospital staff so that the second injection could be administered if the preliminary diagnosis of myocardial infarction was confirmed.
The protocol was approved by local ethics committees, and informed consent was obtained from the patients, in compliance with local regulations.
Assessment of End Points
Overall mortality at 30 days was the primary end point, and death due to cardiac causes (arrhythmic and nonarrhythmic), either before hospital admission or in the hospital, ischemic or hemorrhagic stroke, other bleeding complications, death due to other vascular causes, and death due to other noncardiovascular causes were secondary end points. The cause of death could be determined only for patients who died within the period from randomization to hospital discharge (data were not censored at 30 days); after hospital discharge it was often not possible to determine the cause of death or the patient's vital status. Nonfatal events that occurred from randomization to discharge were also secondary end points: a final diagnosis of myocardial infarction, according to classic criteria (on the basis of the electrocardiogram, enzymes, and case history); nonfatal stroke (computerized tomography was recommended to determine whether the stroke was hemorrhagic or ischemic); heart failure; arrhythmia requiring cardioversion or cardiac pacing; and reinfarction. Data on clinically important complications were also recorded: hypersensitivity reactions, severe bleeding (requiring transfusion), symptomatic hypotension, and other severe adverse events.
Sample Size
The expected benefit of treatment in terms of the primary end point, overall mortality at 30 days, was assumed to depend on two factors -- the time gained by administering the thrombolytic agent before admission rather than in the hospital (the difference between the length of time from the onset of symptoms to prehospital thrombolytic therapy and that from onset to thrombolytic therapy administered in the hospital) and the total time elapsed between the onset of symptoms and the administration of active treatment (the thrombolytic agent)4. Using a simulation method, and assuming that the overall mortality in the control group would be 14 percent, we estimated that a sample of 10,000 patients would enable us to detect a 15 percent reduction in mortality, with a power of 90 percent and an alpha risk of 0.05 (in a two-sided test)19.
In May 1991, after the study had been in progress for 20 months, it became clear that the required number of patients would not be recruited in the 2-year study period originally planned. The Directorate General of the European Economic Community (EEC) granted a one-year extension, to end at the time of the termination of the research program under which the study received funding, at the end of 1991. In addition, the EEC Policy Board was consulted, and it stated that "even with a total number of 5000 to 6000 patients, the results would be worthwhile." The Steering Committee, whose membership included a representative from the EEC Directorate General but not from SmithKline Beecham, thus made the decision to terminate the trial in January 1992.
Mobile Emergency Units and In-Hospital Care
All participating mobile emergency units had a physician on duty in the ambulance, and electrocardiographic and resuscitation equipment, including a defibrillator, was mandatory. Most units were already routinely diagnosing myocardial infarction and transporting patients, and a few had had experience in administering thrombolytic therapy. However, we did not attempt to standardize care beyond these basic elements, and the care provided therefore remained representative of local procedures. Patients who were enrolled were taken to the hospital by the staff of the mobile emergency unit; there they were followed up by the staff of the cardiology ward until discharge.
Collection and Editing of Data
Clinical report forms, forms for the reporting of major adverse events, and supporting data were sent to the EMIP Coordinating Center at regular intervals. The electrocardiogram recorded when the patient was first seen outside the hospital, the first in-hospital electrocardiogram, and that obtained at discharge were collected for centralized validation. Only 4.2 percent of the electrocardiograms were missing or unreadable. The supporting data for all strokes were centrally reviewed, and the strokes were classified by an independent, experienced neurologist.
Statistical Analysis
Intention-to-treat analysis of all data was based on the treatment to which the patient was randomly assigned, irrespective of the actual treatment received or the final diagnosis. Analyses were performed for the pooled strata and the individual strata. Overall mortality at 30 days and mortality from cardiac causes in the two groups were compared with use of chi-square statistics and survival analysis (with the log-rank test); adjustments were made for base-line variables with use of a Cox model. The rates of incidence of the other end points were compared with a chi-square test. The P values given are for two-sided tests.
We also performed a meta-analysis of the data on short-term overall mortality (up to 30 days or discharge) from published and unpublished studies that used standard randomization procedures, comparing strategies for prehospital and in-hospital thrombolytic therapy in patients with suspected acute myocardial infarction. The analysis was performed with use of the exact logarithm of the odds ratio20,21.
Results
From October 1988 through January 1992, 5469 patients were enrolled in the EMIP study by the staff of mobile emergency units operated by 163 centers in 15 European countries and Canada. Over half the patients (56 percent) were enrolled in France, 15 percent in the United Kingdom, 10 percent in Russia, and 5 percent in Germany. A total of 2750 patients were randomly assigned to the prehospital group, and 2719 to the hospital group; 4767 patients (87.2 percent) had ST-segment elevation (2393 in the prehospital group and 2374 in the hospital group) and 702 (12.8 percent) had no ST-segment elevation (357 in the prehospital group and 345 in the hospital group). Just over half the study centers returned completed registries, and from these we calculated that 32 percent of all patients screened were included in the study. The main reason for exclusion was that the length of time between the onset of symptoms and the prehospital injection was longer than six hours.
Short-term follow-up data (up to 30 days or discharge) were available for 5458 patients (99.8 percent). The two groups were balanced in terms of the distribution of base-line characteristics (Table 1). In the prehospital group, 8.2 percent of patients were receiving aspirin before randomization and 78.9 percent after randomization; the same was true for 9.4 percent and 78.7 percent, respectively, in the hospital group. These differences were not statistically significant.
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Accuracy of Prehospital Diagnosis
The second injection was given after the indication for thrombolysis (suspected myocardial infarction) was confirmed by the hospital physician in 92.6 percent of patients in the prehospital group and 92.2 percent in the hospital group. In 2.3 percent and 3.4 percent of patients, respectively, the diagnosis of suspected myocardial infarction was not confirmed, and for the remaining patients thrombolytic treatment was either judged to be contraindicated (2.3 percent and 1.9 percent) or not given for technical reasons (2.8 percent and 2.4 percent). The data on the final diagnosis at the time of discharge or death show that for 87.8 percent of the patients the diagnosis of myocardial infarction was confirmed (Table 1).
Compliance with Study Treatment
A total of 73 randomly assigned patients did not receive any study treatment (39 in the prehospital group and 34 in the hospital group). The main reasons were rapid deterioration in the patients' condition and technical difficulties (such as broken treatment vials or problems with the microcomputer). Complete study treatment (both injections) was administered to 90.7 percent of the patients (4961 of 5469); 343 patients received only the first injection, but 89 of them died before the second injection could be administered (Table 1).
Major and Minor Complications
During the period before admission, there was a significant excess of ventricular fibrillation (Table 2) and some minor adverse events in the prehospital group as compared with the hospital group (data not shown).
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For some minor complications (such as symptomatic bradycardia), an initial excess rate during the period before admission in the prehospital group was offset by an excess in the hospital group during the in-hospital period; there was no significant difference in overall incidence. For other minor complications, the overall incidence remained higher in the prehospital group than the hospital group (data not shown).
The higher incidence of ventricular fibrillation during the period before hospital admission among patients in the prehospital group, although statistically significant, was offset by a higher incidence of this complication in the hospital group during the hospital period; as a result, there was no significant difference in overall incidence (Table 2). The incidence of cardiac arrest and shock showed a similar trend. The overall incidence of at least one severe cardiac complication was similar in both groups (30.0 percent in the prehospital group vs. 29.2 percent in the hospital group, P = 0.50).
Overall 30-Day Mortality and Mortality from Cardiac Causes
A 13 percent lower rate of overall mortality at 30 days was observed in the prehospital group, but this difference was not statistically significant (P = 0.08 by the log-rank test) (Figure 1). When the difference in this rate was adjusted for base-line variables in a Cox model, the study treatment had no significant effect (P = 0.13). In subgroup analyses performed in the two strata (ST-segment elevation vs. no ST-segment elevation), the overall 30-day mortality was found to be similar. The time of death was found to be similar for both groups, and a nonsignificant excess of deaths before admission in the prehospital group was offset by a significant excess of in-hospital deaths in the hospital group (Table 3).
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Results from EMIP and Similar Studies
Four other studies of prehospital thrombolytic therapy found trends similar to those we observed10,13,22,23. Analysis of the combined results showed a reduction of 17 percent in overall short-term mortality (95 percent confidence interval, 2 to 29 percent; P = 0.03) among the patients who received thrombolytic therapy before admission (Table 5).
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Our results confirm that the administration of thrombolytic therapy for acute myocardial infarction by emergency medical personnel is feasible and safe in many settings. Although not statistically significant, the observed net gain of 15 lives for every 1000 patients treated before admission to the hospital is consistent with our initial hypothesis that earlier thrombolytic treatment would result in a reduced mortality rate. All patients received the same thrombolytic therapy. The difference between the groups was in when the therapy was administered; therefore, the lower mortality rates in the prehospital group can be attributed to this factor. Moreover, the gain of approximately one hour between the administration of thrombolytic therapy in the prehospital and hospital groups is the smallest gain that might be expected in a real-life situation. The median "door-to-needle time" -- the delay between hospital admission and injection -- was 15 minutes, which is the shortest delay that could be expected in hospitals where the most streamlined procedures are used. In most hospitals the median door-to-needle time is in the range of 30 to 90 minutes7,10,13,14,15,16,24,25,26.
The fact that we had to terminate the study after the enrollment of only half the planned number of patients may explain why the 13 percent reduction in short-term mortality from all causes in the prehospital group did not reach statistical significance (P = 0.08) and why the 16 percent reduction in mortality from cardiac causes in this group was of only borderline significance (P = 0.049). In one recent study of only 300 patients, a significant difference in overall mortality was found22; the median length of time between the two injections was longer than in the EMIP study (130 vs. 55 minutes). In our study, in the subgroup of patients for whom the delay was the longest (90 minutes or more between injections), a significant 42 percent reduction in overall mortality was observed (P = 0.047) (Table 4). With the increased statistical power achieved by combining five studies, we were able to confirm the trend observed in our study: in the five studies combined, there was a significant 17 percent reduction in short-term mortality among patients who received thrombolytic therapy before they reached the hospital (P = 0.03).
The incidence of major complications (bleeding and strokes) was similar in the two groups and was also similar to that observed in the anistreplase group in the Third International Study of Infarct Survival (ISIS-3) (1.3 percent at 35 days)27. For some minor complications, a higher incidence was observed in the prehospital group during the period before admission, but it was of no clinical consequence. A higher incidence of ventricular fibrillation in the prehospital group before admission was offset by a higher incidence of this complication during hospitalization in the hospital group. That ventricular fibrillation was more common after the injection of the active drug suggests that the thrombolytic agent had a role in triggering the arrhythmia. Reperfusion-induced arrhythmia is a well-known phenomenon in experimental studies but has rarely been reported in clinical studies28. In other trials the overall incidence of ventricular fibrillation was the same in both study groups, although the varying lengths of observation time, from a few hours to one or two weeks, could explain the different rates reported1,3,29,30. Other differences in the frequency of minor adverse events may be due to differences in monitoring, settings, and procedures.
The reliability of diagnosis in the prehospital setting is demonstrated by the fact that 90 percent of the patients were ultimately determined to have certain or probable myocardial infarction and an additional 7 percent to have acute coronary disease. In our study, a 12-lead electrocardiogram was mandatory for inclusion in the study, and each patient's eligibility was evaluated by a physician. It is difficult to compare the rate of erroneous diagnosis among various trials, since such data have rarely been reported. In the Thrombolysis Early in Acute Heart Attack Trial (TEAHAT), for example, in which a 12-lead electrocardiogram was not always obtained before admission, the conditions of over 40 percent of the patients were misdiagnosed, whereas in the first study by the Gruppo Italiano per lo Studio della Streptochinasi nell'Infarto Miocardico (GISSI-1) 94 percent of patients received a correct diagnosis1,14. Therefore, in the EMIP trial, the ability of the emergency medical teams to diagnose myocardial infarction correctly was similar to that of the hospital teams.
In conclusion, patients with suspected myocardial infarction who are seen within six hours of the onset of symptoms by the staff of a mobile emergency unit can safely receive thrombolytic therapy, if a 12-lead electrocardiogram is obtained and the diagnosis is made by an experienced physician. If thrombolytic therapy is to be used, however, we strongly recommend that a defibrillator be available in the ambulance. These results cannot be generalized to geographic areas without staff and equipment similar to those in the EMIP centers. Nonetheless, where the necessary personnel and equipment are available, we recommend that thrombolytic therapy be administered by the emergency medical team, before the patient arrives at the hospital, since it has some benefit in reducing mortality from cardiac causes and possibly also overall mortality.
Supported by a contract (MR4*-031-F) with the European Economic Community Directorate General for Science, Research, and Development and by a grant from SmithKline Beecham Pharmaceuticals, which had no part in the design, conduct, or monitoring of the study or in the analysis, interpretation, or reporting of the results.
Source Information
Preliminary results were presented in part at the Scientific Sessions of the American College of Cardiology, Dallas, April 12-16, 1992.This report was prepared by A. Leizorovicz, J.P. Boissel, D. Julian, A. Castaigne, and M.C. Haugh. The members of the European Myocardial Infarction Project (EMIP) Group are listed in the Appendix.
Address reprint requests to the EMIP Group, Unite de Pharmacologie Clinique, B.P. 3041, 69394 Lyon CEDEX 03, France.
References
The members of the EMIP Group were as follows (some national coordinators were also investigators):
Austria: National coordinator -- P. Kuhn (Linz); investigators -- Salzburg: K. Atzenhofer-Baumgartner, F. Chmelizek, F. Schnoll, and C. Ursin; and Steyr: O. Grobl, A. Hamberger, R. Kissling, G. Kleinberger, E. Laich, S. Lechner, R. Leeb, and R. Zenz.
Belgium: National coordinators -- G. De Backer and W. Buylaert (Ghent), L. Bossaert (Edegem); investigator -- Namur: G. Fautsch.
Canada: National coordinator -- M. Kalina (Montreal); investigators -- Montreal: M. Afilalo, J. Barriault, J. Brophy, D. Fitchett, D. Grossard, P. Laramee, Y. Latour, T. Leibovici, and C. Maranda.
Denmark: National coordinator -- G. Jensen (Hvidovre); investigator -- Copenhagen: J. Wagner.
Finland: National coordinator -- A. Kinnunen (Helsinki); investigators -- Helsinki: P. Pajunen and J. Erosuo.
France: National coordinators -- A. Castaigne (Creteil) and C. Herve (Paris); investigators -- Aix-en-Provence: E. Rodriguez; Angers: J.L. Chassevent and J. Mylonas; Annecy: P. Leveau and R. Normand; Annonay: P.L. Blanc; Arles: R. Dubuisson; Arpajon: M. Rocheman; Arras: F. Thibaut; Aubenas: O. Lepine; Auch: E. Contreras; Avignon: K. Chatawi and P. Olivier; Bayonne: P. Gaudeul and P. Mathieu; Beaune: Y. Galloux; Belfort: A. Kara; Belley: O. Florent; Bourges: T. Chaumeron and R. Durand; Brive: P. Nauche; Caen: J.M. Hurpe; Calais: H. Peneau and F. Thieuleux; Carcassonne: P. Lepennois; Chateauroux: R. Parisot and L. Soulat; Clermont-Ferrand: A. Richard; Clichy: A. Haegel; Corbeil-Essonnes: M. Bray; Creil: A. Dufort; Creteil: M. Gaillard; Dijon: J.C. Foissac and E. Petit-Remy; Epernay: J.M. Le Coz; Epinal: H. Tonnelier; Feurs: G. Kruszinski and J. Porte; Gap: N. Benchehida; Garches: P. Coninx, E. Lanata, and J. Pasteyer; Gueret: G. Bessede, D. Fressard, and L. Mansour; Guingamp: P. Le Roux; Helfaut: D. Dubois; La Rochelle: J. Depaire and S. Dulioust; Lagny-sur-Marne: Y. Guittard; Le Mans: B. Coudert and D. Dubois; Lens: P. Pignon and G. Vermesse; Limoges: P.B. Petitcolin; Longjumeau: J.M. Coudray; Lorient: C. Durand; Lyons: M. Bertin, M. Gallon, G. Prost, and H. Milon; Maubeuge: M.C. Mazzolini; Meaux: J.L. Petit and P. Quillet; Melun: M.C. Porta; Metz: M. Condi and J. De Cubber; Mont-de-Marsan: M. Cazaugade and A. Haurie; Montbrison: J.P. Chaussinand and J.M. Pages; Montlucon: G. Hufnagel and S. Provenchere; Moutiers: R. Richardot; Nancy: P.E. Bollaert; Nantes: J.L. Landas; Nevers: J.M. Cachera and F. Guillet; Nice: D. Grimaud, P. Melandri, and P. Morand; Nimes: J. Hertault and M. Romieu; Niort: P. Vidal; Orsay: P. Goeringer; Paris: B. Debien, H. Julien, J. Juniere, P. Le Dantec, and P. Menage; Perigueux: J.P. Larque; Perpignan: Y. Garcia and M.J. Raynal; Poitiers: D. Baudier; Reims: B. Journe; Rennes: C. Hamon and C. Saint-Marc; Roanne: J.C. Ducreux and G. Tempelhoff; Romans: G. Bonnefoy and G. Michelon; Saint-Brieuc: Y. Cotel; Saint-Etienne: J.L. Blanc, E. Chastel, H. Decousus, S. Laporte, and J.L. Pugnet; Saint-Lo: C. Mathurin and G. Roussel; Saint-Malo: J. Kolb; Saint-Michel: G. Mottet; Saint-Quentin: J.P. Halgrain; Sainte-Affrique: P. Chevalier; Sarrebourg: L. Dreyfuss; Senlis: J.M. Farnos, M. Martignon, and G. Meyer; Soissons: D. Lansoy; Strasbourg: H. Gros, J.M. Mossard, and M. Muhlmann-Weill; Thonon-les-Bains: B. Delavenna, M.C. Dufour, and B. Joyeux; Valence: P. Achache, P. Fichter, L. Gabrielle, A. Grand, F. Guillaumee, J.F. Huret, P. Jullian, J.M. Laye, P. Mayrand, J.L. Moreau, and L. Vidil; Vienne: L. Ollivier, A. Serusclat, and B. Veyre; Villefranche: C. Combe and N. Smolski; Villeneuve-les-Escaldes: V. Dorion; and Voiron: J.C. Guignon.
Germany: National coordinators -- W. Kasper (Freiburg) and K. Kothe (Berlin); investigators -- Bad Mergentheim: H.D. Bundschuh; Berlin: D. Krausch; Bruchsal: F. Heinrich; Darmstadt: P. Doenecke and A. Raftopoulo; Emmendingen: A. Mann; Freiburg: M. Gundlach; Jena: R. Thiele; Koln: H.W. Hopp; Koln-Meerheim: A. Lechleitner; Konigs Wusterhausen: J. Ruffert; Ludwigshafen: J. Senges; Schopfheim: T. Zeller; Tuttlingen: M. Schipulle; Villingen-Schwenningen: K. Lang; Wetzlar: P. Rawer; Wittenberg: H. Libuda; and Zossen: J. Scholz.
Greece: National coordinators -- P. Toutouzas and D. Kremastinos (Athens); investigators -- Athens: A. Androulakis, I. Fotiadis, E. Iliodromitis, and C. Stratos; Chalkis: I. Mantas; Karditsa: A. Karras; Rhodes: D. Papakonstantinou; and Volos: T. Tsaknakis.
Italy: National coordinator -- M. Marzilli (Pisa); investigators -- Casarano: G. Pettinati; Formia: F. Carta; Montfalcone: M. Palmieri; Novara: P. Rossi; Parma: G. Botti; Pescia: L. Papi; Ravenna: S. Coccolini; Tricase: A. Galati and F. Leo; and Udine: G.A. Feruglio.
Latvia: National coordinator -- M. Anshelevich (Riga); investigators -- Daugavpils: E. Kisliak and A. Kurilko; and Riga: I. Alka and I. Pokrovskaia.
Luxembourg: National coordinator -- J. Erpelding (Luxembourg); investigators -- Esch-Alzette: J. Uhrig; Ettelbruck: M. Jaminet; and Luxembourg: J. Bisdorff and C. Merten-Glodt.
Portugal: National coordinator -- R. Seabra-Gomes (Carnaxide); investigators -- Carnaxide: V. Gil, M. Mendes, and A. Silva; and Lisbon: V. Araujo, J. Carmona, M. Correia, A. da Paula, A. Diogo, R. Guimaraes, M. Lopes, P. Loureiro, J. Mota, E. Mourao, L. Mourao, F. Padua, J. Quininha, J. Rato, C. Ribeiro, R. Rodrigues, L. Santos, and R. Sergio.
Russia: National coordinator -- S. Varshavsky (St. Petersburg); investigators -- Barnaul: A. Timofeev; Irkutsk: V. Fialkovsky; Penza: V. Uliakhyna; Saratov: O. Orlikova; and St. Petersburg: T. Brenner, V. Bzhelianskaia, S. Feldman, A. Kuptsova, O. Loginovskaia, L. Sorokin, and S. Urazgildeeva.
Spain: National coordinator -- F. Navarro-Lopez (Barcelona); investigators -- Barcelona: X. Bosch Genover, S. Ferrandis, A. Lopez, L. Margarit, J. Motos, and M. Rodriguez; and Madrid: L. Lopez-Bescos.
Switzerland: National coordinator -- R. Malacrida (Bellinzona); investigators -- Basel: C. Gradel; and Zurich: M. Genoni.
United Kingdom: National coordinator -- D. McC. Boyle (Belfast); investigators -- Ballymena: C. Wilson; Belfast: D. Archer, M. Cave, and D. Higginson; Craigavon: K. Balnave; Dungannon: M. McNamaee; Enniskillen: M. Varma; Londonderry: H.M. Dunn; Magherafelt: N.C. Chaturvedi; Newry: A. Devlin; and Omagh: C. Russell.
Coordinating Center (Lyons, France): J.P. Boissel, A. Leizorovicz, C. Payen, J.P. Teppe, C. Goubier-Vial, Z. Akkal, A. Akkal, F. Janot, F. Martin, Y. Alamercery, J. Maupas, I. Njeim, P. Chevarier, T. Ducruet, C. Mercier, L. Lion, and M.C. Haugh.
Project-management Committee: All national coordinators; two representatives from the Coordinating Center (J.P. Boissel and A. Leizorovicz); and D. Chamberlain and R. Vincent (Brighton, United Kingdom); P. Sellier (Paris, France); and K. Vuylsteek (EEC; Ghent, Belgium).
Policy Board: Chair -- D. Julian (London); J. Lubsen (Rotterdam, the Netherlands); M. Samama (Paris); P. Sleight (Oxford, United Kingdom); G. Tognoni (Milan, Italy); and N. Victor (Heidelberg, Germany).
Validation of Critical Neurologic Events: N. Nighoghossian (Lyons, France) and M. Hommel (Grenoble, France).
Poison Information Center (Lyons, France): J. Descottes and J.M. Sapori.
Commission of the European Communities, Directorate General for Science, Research, and Development (Brussels, Belgium): A.E. Baert, C. Baya, M. Hallen, and V. Thevenin.
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Related Letters:
Prehospital Thrombolytic Therapy for Myocardial Infarction
Fath-Ordoubadi F., Solomon S. D., Antman E.
Extract |
Full Text
N Engl J Med 1994;
330:290-291, Jan 27, 1994.
Correspondence
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