ORIGINAL ARTICLE
Prehospital triage for angiography-gu ided
therapy for acute myocardial infarction
N.M.S.KJ. Ernst, M.J. de Boer, A.W.J van 't Hof, F. Hollak, H. van de Wetering, J.H.E. Dambrink, J.C.A. Hoornje, H. Suryapranata, F. Zijlstra
Background. Time between symptom onset and effective reperfusion is of paramount importance in patients with acute myocardial infarction (MI) treated with reperfusion therapy. In the PHIAT (Pre-Hospital Infarction Angioplasty Triage) project, safety and feasibility of in-ambulance electrocardiography facilities for prehospital triage for direct transfer to an interventional centre to undergo immediate coronary angiography and angiography-guided therapy were evaluated. Methods and results. The ambulances were equipped with a defibrillator and electrocardiography unit with computerised electrocardiographic analysis. Patients with acute MI symptoms and fulfilling certain criteria compatible with a large MI were induded and pretreated with heparin and aspirin during transportation. During the study period, 284 patients were included. Eleven percent did not have an acute MI. PCI, performed in 94% (n=239) ofthe patients, was successful in 94%. Prehospital triage reduced time to treatment. In 32% of the patients triage resulted in direct transportation to the interventional centre instead of to the nearest community hospital. All-cause mortality was 9% after a mean follow-up of nine months. No serious bleeding complications were seen.
N.M.S.K.J. Emst M.J. de Boer A.W.J. van 't Hof J.H.E. Dambrlnk J.C.A. Hoomtje H. Suryapranata F. Zljilstra Isala Clinics, De Weezenlanden Hospital, Department of Cardiology, Groot Wezenland 20, 8011 JWZwolle F. Hollak H. van de Weterlng Regional Ambulance Service IJssel-Vecht B. V. Zwolle
Correspondence to: M.J. de Boer E-mail: [email protected]
Netherlands Heart Journal, Volume 12, Number 4, April 2004
Conclusion. Prehospital triage in the ambulance is safe and feasible. A stiking percentage (11%) ofthe identified patients does not have an acute MI and this is more than has been reported from prehospital thrombolysis trials. (Neth Heart J 2004;12:151-6.) Key words: myocardial infarction, prehospital triage, primary angioplasty
the time between onset of symptoms and achievement of complete reperfusion is of paramount importance for survival and recovery of left ventricular function after thrombolytic therapy for acute myocardial infarction."l2 A similar relation has also been demonstrated for reperfusion therapy by means of primary coronary angioplasty,3'7 although the outcome with regard to mortality seems less time-dependent in patients treated with primary angioplasty compared with patients treated with thrombolysis.8'9 In 1993, the first randomised trials comparing immediate coronary angioplasty with thrombolytic therapy in acute myocardial infarction reported a better clinical outcome with an immediate coronary angioplasty strategy.3'4 Compared with thrombolytic therapy, primary coronary angioplasty may be regarded as a better reperfusion therapy as it is associated with lower early and late mortality, a lower rate ofnonfatal reinfarction, fewer readmissions for recurrent ischaemia or heart failure and lower total medical costs. These benefits were sustained at longterm follow-up.'0 An advantage ofthrombolytic therapy is that it can already be started in the prehospital setting by general practitioners and paramedical ambulance staff, which may result in a reduction in time from onset of symptoms to start of reperfusion therapy."'1-3 Contrary to lytic therapy, a disadvantage of primary coronary angioplasty is that it can only be performed in a limited number of specialised centres. Patients presenting to a centre without coronary angioplasty facilities may therefore need immediate additional transfer to such 151
Prehospital triage for angiography-guided therapy for acute myocardial infarction
WPW or LBBB or IV-conduction block or pacemaker rhythm H
yes
No
>0.2 mV ST elevation in >2 leads V1-V6 and >0.3 mV ST elevation in >1 lead Vi-V6 Yes
Sum of ST elevation in V1-V6 plus Sum of ST depression in 11, 111, aVF .0.8
I~~~~~~~~~~ V
zICz
mV
No
A Yes
.0.1 mV ST elevation in .2 leads 11, 111, aVF and .0.2 mV ST elevation in .1 lead 11, Ill, aVF
No PTCA
0
-No
I
I Yes
Sum of ST elevation in 1-111, aVF plus Sum of ST depression in V1-V4 .0.6 mV
No
Figure 1. ECG algorithm used in the PHIAT (Pre-Hospital Infarction Angioplasty Triage) project. a specialised centre. This results in an extra time delay before reperfusion therapy can be delivered. We introduced in-ambulance electrocardiography and analysis facilities for prehospital triage for direct transfer to our hospital for patients with acute myocardial infarction to undergo immediate coronary angiography and subsequent angiography-guided therapy. This study evaluated the safety and feasibility of this ambulance triage project.
152
Methods In the PHIAT (Pre-Hospital Infarction Angioplasty Triage) project, initially six and finally all 15 ambulances in the Zwolle region were equipped with a defibrillator and electrocardiography unit (Corpuls-Schiller) with
computerised electrocardiographic (ECG) analysis using the algorithm depicted in figure 1. Two ambulances from a neighbouring region (at a mean distance of 30 kilometres from our hospital) also took part in the registry.
Netherlands Heart Joumal, Volume 12, Number 4, April 2004
Prehospital triage for angiography-guided therapy for acute myocardial infarction
Patients with symptoms of an acute myocardial infarction for at least 30 minutes and fulfilling the criteria from the computer algorithm were included. Patients having symptoms for more than 24 hours at presentation and patients older than 80 years were excluded. Contraindications for thrombolytic therapy, previous myocardial infarction or bypass surgery were not reasons to exclude patients from the registry. All ambulance personnel completed a training programme to carry out high-quality ECGs. If the ECG analysis by the automated algorithm fulfilled the positive identification criteria as shown in figure 1, an immediate call to the central ambulance unit was followed by administration of 10,000 IU heparin and 500 mg aspirin intravenously and A-I (very urgent) transport to our hospital. The central ambulance unit communicated the expected time of arrival to our hospital to allow preparation ofthe coronary care unit, the catheterisation laboratory, auxiliary personnel and the interventional cardiologist on call. Data on time intervals, patient characteristics and clinical outcome were registered in a dedicated database. An acute myocardial infarction was defined as the presence of a positive ECG combined with an unstable coronary lesion at acute angiography and/or the presence of enzymatic myocardial damage, defined as an increase in creatinine kinase of at least two times the upper limit ofnormal. Transportation distances were calculated using postal codes from the locations where the diagnosis of the acute myocardial infarction was made and postal codes from the various hospitals. TIMI flow grade and the degree of residual stenosis were visually assessed by the interventional cardiologist as well as by the angiographic core laboratory. Success of the primary PCI was defined as the presence of TIMI flow grade 3 after the procedure and a residual stenosis of less than 50%. Left ventricular ejection fraction was measured in our nuclear laboratory using a technique with Technetium-labelled red blood cells, as previously described.3'5"0 Results
Clinical characteristics From 15 November 1998 to 31 December 2000,284 patients fulfilled the PHIAT criteria for acute myocardial infarction. One patient died before arrival in the hospital (autopsy was not performed, cause of death unknown). Clinical characteristics of the remaining 283 patients are shown in table 1. The mean age ofthe patients was 62±12 years (range 16 to 83 years). Twenty-three patients (8%) of the total group of 284 patients did not have angiographic confirmation of acute myocardial infarction and the absence of acute myocardial infarction was confirmed by repeated enzyme measurements. In seven patients (2.5%) no coronary angiography was performed, because the
Netherlands Heart Journal, Volume 12, Number 4, April 2004
Table 1. Clinical characteristics of 283 patients who fulfilled PHIAT criteria.
Male Hypertension Diabetes mellitus Smoking Hypercholesterolaemia Family history CAD Previous myocardial infarction Previous PCI Previous CABG Previous stroke Killip class I at admission Killip class II at admission Killip class Ill at admission Killip class IV at admission
n
%
211 87 34 141 56 117 33 14 14 12 253 10 16 4
74 31 12 50 20 41 12 5 5 4 89 4 6 1
CAD=coronary artery disease, PCI=percutaneous transluminal coronary angioplasty, CABG=coronary artery bypass grafts.
Table 2. Diagnoses of 'false-positive' patients who fulfilled PHIAT criteria.
Pericarditis
Supraventricular arrhythmia Atypical chest pain/early repolarisation on electrocardiogram No signs of coronary artery disease on acute angiography Presence of coronary artery disease on acute angiography, no unstable lesion Aortic valve stenosis, left ventricular hypertrophy Myocarditis/congestive heart failure Total
n
%
1 2
3 7
4
13
2
7
15
50
4 2 30
13 7 100
patient's clinical condition on admission and repeated electrocardiography and enzyme measurements confirned the absence of an acute myocardial infarction. Definitive clinical diagnoses ofthese 30 'false-positive' patients are shown in table 2. From the remaining 254 patients with a confirmed diagnosis of an acute myocardial infarction, 46% suffered from an anterior wall myocardial infarction. Treatment From the group of 254 patients with an acute myocardial infarction 251 patients (99%) underwent immediate coronary angiography (i.e. immediately after admission); from the remaining three patients, in153
Prehospital triage for angiography-guided therapy for acute myocardial infarction
at-100
-100
-
= 1.
c7
95f
=
90-
x
-L
=
90 en
2
4
6
8
10
12 Months
Figure 2. Kaplan-Meier curve for all-cause mortality from 284 patients who fulfilled the PHIATcriteria.
cluding the one who died in the ambulance before arrival in the hospital, one patient was known to have extensive three-vessel coronary artery disease, not amenable to percutaneous or surgical intervention, and one patient suffered from an acute myocardial infarction due to atrial fibrillation with a rapid ventricular response and a severe aortic stenosis. In this patient coronary angiography was performed at a later stage as prelude to cardiac surgery. From the group of patients with a confirmed diagnosis of an acute myocardial infarction, 239 patients (94%) were treated with primary coronary intervention (PCI). Bypass surgery was performed during the initial admission in five patients (2%). Eight patients (3%) were treated conservatively (i.e. no primary PCI or bypass surgery). Time intervals The mean door-to-balloon time for the patients treated with primary PCI was 43 minutes (25th percentile 27 minutes, median 39 minutes, 75th percentile 50 minutes). From the group of 254 patients with an acute myocardial infarction, 214 patients (84%) had symptoms for less than six hours before admission. The mean duration from start of symptoms to admission was 140 minutes, and the mean total ischaemic time, defined as time from symptom onset to first balloon inflation, was 183 minutes.
Angiographic and clinical outcome At acute coronary angiography the following TIMI flow grades of the infarct-related vessel pre-PCI were seen: TIMI flow grade 0 in 129 patients (5 1%), TIMI flow grade 1 in 24 patients (10%), TIMI flow grade 2 in 38 patients (15%) and TIMI flow grade 3 was seen in 60 patients (24%). The primary PCI procedure was successfuil in 224 patients (94%). In 207 patients (8 1%) nuclear ejection fraction was measured within three 154
80 ; ,
6
12 Months
Figure 3. Kaplan-Meier curve for surpival without reinfarction for 284 patients who fulfilled the PHMATcriteria.
days after admission. The mean ejection fraction was 45% (range 17 to 70%). With respect to all-cause mortality of all patients who fuffilled the ambulance criteria the following was seen: 16 patients (6%) died during first admission (inhospital mortality) and, as already mentioned, one patient died before admission. With a mean follow-up of one year, 25 patients (9%) died (figure 2). The Kaplan-Meier curve for survival without the occurrence of reinfarction is shown in figure 3. All 284 patients who fulfilled the ambulance criteria for acute myocardial infarction were given heparin and aspirin intravenously in the ambulance during transportation. No bleeding complications (including stroke) were seen in any of the patients in the prehospital phase. None of the patients experienced a serious bleeding complication during admission until the acute coronary angiography and primary PCI.
Discussion Data from this PHIAT project show that ambulance personnel are capable of diagnosing acute ST-elevation myocardial infarction in almost 90% of patients by doing an electrocardiogram in the prehospital phase. Using the PHIAT protocol, after equipping and training of ambulance personnel, patients with large myocardial infarctions (i.e. large cumulative STsegment deviation) can be referred directly and safely to an interventional centre. A striking percentage of the patients (11%) who fulfilled the PHIAT criteria did not have angiographic confirmation of an acute myocardial infarction and the absence of an acute myocardial infarction in these patients was confirmed by repeated enzyme tests. This is a higher percentage than has been reported from
prehospital thrombolysis trials.13'15 The total ischaemic time of patients with acute myocardial infarction treated with primary coronary Netherlands Heart Journal, Volume 12, Number 4, April 2004
Prehospital triage for angiography-guided therapy for acute myocardial infarction
angioplasty is a combination ofpatient delay, response delay of the primary care system, transportation delay, and the time needed to establish reperfusion in the catheterisation laboratory.'6 Prehospital triage is associated with a reduction in total ischaemic time compared with patients seen primarily in the emergency room or referred from one of the surrounding community hospitals without interventional facilities.'6 If no prehospital triage were performed, 82 patients (32%) with an acute myocardial infarction would initially have been admitted to the nearest community hospital without interventional facilities leading to an additional delay in the local emergency room and during subsequent transportation to our hospital. If these patients had been referred to our hospital via the nearest community hospital the transportation distance would have increased from an actual distance of 32±9 kilometres to a distance of 51±11 kilometres. The extra (mean) transportation distance of 19 kilometres plus the mean in-door-out-door-time at the noninvasive centre, which is about 45 minutes as is known from Air Primary Angioplasty in Myocardial Infarction (AirPAMI) and the DANish trial in Acute Myocardial Infarction (DANAMI-2) studies,'7"18 therefore results in a mean gain of at least 60 minutes. This time must be added to the extra time gained due to making prehospital infarct diagnosis leading to a reduction in door-to-balloon-time. Data from the National Registry of Myocardial Infarction (NRMI-2 registry) of more than 27,000 patients from 661 hospitals in the United States clearly showed the relationship between increased mortality and delay in door-to-balloon time,'9 especially when door-to-balloon time is greater than 120 minutes. Door-to-balloon time was longer than two hours in nearly 50% of the patients in this cohort. In our data the mean door-to-balloon time was only 43 minutes due to preparation of staff starting after announcement of the patient's time of arrival by the ambulance service. Although it was shown in DANAMI-2 that with a transportation time of three hours to an interventional centre primary PCI is still superior to in-hospital thrombolysis in a noninterventional centre, time gain remains of paramount importance. According to the observed high patency rate of the infarct-related vessel at acute angiography before primary PCI, it can be concluded that this prehospital reperfusion had occurred in more patients than was anticipated. The role of the administration of intravenous heparin pre-PCI with respect to this issue showed conflicting results in previous observations.20'2' However, recently it was shown that prehospital administration of heparin and aspirin resulted in a higher initial patency of the infarct-related artery in patients with acute myocardial infarction.22 As data on left ventricular ejection fraction are not complete, no reliable conclusions on the preservation of the left ventricular function or the relation with the initial patency can be made. Netherlands Heart Journal, Volume 12, Number 4, April 2004
Although the all-cause mortality seems relatively high, it should be considered that only patients with large acute myocardial infarction, of whom 46% were suffering from an anterior myocardial infarction (i.e. selection of high-risk population), were included in the PHIAT project. Only one patient died in the prehospital phase. Furthermore, patients with Killip class III and IV were not excluded from study entry, and neither were elderly people up to 80 years. Thrombolytic therapy is still restricted for selected patients filfilling strict inclusion criteria and leads to more bleeding complications, a modest reperfusion rate and a worse clinical outcome compared with primary coronary angioplasty.8l2,23 26 As our data show, the intravenous administration of heparin and aspirin in the ambulance did not lead to any (major) bleeding complication whereas contraindications for thrombolytic therapy were no reason to exclude patients. The logistics and clinical problems regarding referral of patients for primary coronary angioplasty from hospitals without interventional facilities have been described before.27
Several issues remain to be studied further: the comparison of prehospital thrombolysis with prehospital triage guided primary coronary angioplasty and the effect of primary coronary angioplasty facilitated with early treatment with specific agents such as thrombolytic agents and/or glycoprotein IIb/IIIa receptor blockers. The first trial to compare prehospital thrombolysis with primary coronary angioplasty in patients with acute myocardial infarction recently showed inconclusive results.28 The Comparison ofAngioplasty and Prehospital Thrombolysis In acute Myocardial infarction (CAPTIM) Investigators reported that patients who received prehospital thrombolysis showed a trend towards more reinfarctions but fewer deaths compared with the patients treated with primary angioplasty. The Abciximab before Direct angioplasty and stenting in Myocardial Infarction Regarding Acute and Long-term follow-up (ADMIRAL) trial strongly suggests a positive effect of glycoprotein IIb/IIIa receptor blockers, only when they are administered before arrival in the hospital.29 Conclusions Prehospital triage in the ambulance for patients with acute myocardial infarction is a safe, effective and feasible way to identify patients who are candidates for primary coronary angioplasty, and leads to an important reduction in ischaemic time. Eleven percent of the identified patients do not have an acute myocardial infarction. Further attention needs to focus on this high number of patients without a confirmed diagnosis of acute myocardial infarction, in particular as unnecessary treatment may be harmful. i
155
Prehospital triage for angiography-guided therapy for acute myocardial infarction
Acknowledgements The authors would like to thank Mrs Vera Derks for her excellent secretarial assistance in preparing the manuscript. References Simoons ML, Serruys PW, Brand M van den, Res J, Verheugt FWA, Krauss XH, et al. Early thrombolysis in acute myocardial infarction: Limitation ofinfarct size and improved survival. JAm Coll Cardiol 1986;7:717-28. 2 Boersma E, Maas ACP, Deckers JW, Simoons ML. Early thrombolytic treatment in acute myocardial infarction: reappraisal of the golden hour. Lancet 1996;348:771-5. 3 Zijlstra F, Boer MJ de, Hoorntje JCA, Reiffers S, Reiber JHC, Suryapranata H. A comparison ofimmediate coronary angioplasty with intravenous streptokinase in acute myocardial infarction. N EnglJMed 1993;328:680-4. 4 Grines CL, Browne KF, Marco J, Rothbaum D, Stone GW, O'Keefe J, et al for the Primary Angioplasty in Myocardial Infarction Study group. A comparison of immediate angioplasty with thrombolytic therapy for acute myocardial infarction. NEn,glJMed 1993;328:673-9. 5 Boer MJ de, Suryapranata H, Hoorntje JCA, Reiffers S, Liem AL, Miedema K, et al. Limitation of infarct size and preservation of left ventricular function after primary coronary angioplasty compared with intravenous streptokinase in acute myocardial infarction. Circulation 1994;90:753-61. 6 O'Neill WW, Boer MJ de, Gibbons RJ, Holmes DR, Timmis GC, Sachs D, et al. Lessons from the pooled outcome of the PAMI, Zwolle and Mayo clinic randomized trials of primary angioplasty versus thrombolytic therapy of acute myocardial infarction. J Invasive Cardiol 1998;10:4-10. 7 Berger PB, Ellis SG, Holmes DR, Granger CB, Criger DA, Betriu A, et al, for the GUSTO-II investigators. Relationship between delay in performing direct coronary angioplasty and early clinical outcome in patients with acute myocardial infarction. Results from the Global Use of STrategies to open Occluded arteries in acute coronary syndromes (GUSTO-IIb) trial. Circulation 1999;100: 14-20. 8 Zijlstra F, Patel A, Jones M, Grines CL, Ellis S, Garcia E, et al, for the PCAT collaboration. Clinical characteristics and outcome of patients with early (4h) presentation treated by primary coronary angioplasty or thrombolytic therapy for acute myocardial infarction. EurHeartJ2002; 23:5507. 9 Bertrand ME, McFadden EP. Late is perhaps not... too late for primary PCI in acute myocardial infarction. EurHeartJ2002;23: 1146-8. 10 Zijlstra F, Hoorntje JCA, Boer MJ de, Reiffers S, Miedema K, Ottervanger JP, et al. Long-term benefit of primary angioplasty as compared with thrombolytic therapy for acute myocardial infarction. NEnglJMed 1999;341:1413-9. 11 Rawles JM. Quantification of the benefit of earlier thrombolytic therapy: five-year results ofthe Grampian Region EarlyAnistreplase Trial (GREAT). JAm Coll Cardiol 1997;30:1181-6. 12 Leizorovicz A, Haugh MC, Mercier C, Boissel JP. Pre-hospital and hospital time delays in thrombolytic treatment in patients with suspected acute myocardial infarction. Analysis of data from the EMIP study. European Myocardial Infarction Project. Eur Heart 1
J1997;18:248-53. 13 Boersma E, Maas AC, Hartman JA, Ilmer B, Vos J, Simoons ML. Twelve year triage and thrombolysis treatment prior to hospitalization for myocardial infarction patients in the Rotterdam area ofthe Netherlands: outstanding short-term and long-term results.
14 O'Rourke MF, Cook A, Carroll G, Gallagher D, Hall J. Accuracy of a portable interpretive ECG machine in diagnosis of acute evolving myocardial infarction. Aust NZJMed 1992;22:9-13. 15 Grijseels EWM, Bouten MJM, Lenderink T, Deckers JW, Hoes AW, Hartman JAM, et al. Pre-hospital thrombolytic therapy with either alteplase or streptokinase. Practical applications, complications and long-term results in 529 patients. Eur Heartj 1995; 16:1833-8. 16 Zijlstra F. Long-term benefit ofprimary coronary angioplasty compared to thrombolytic therapy for acute myocardial infarction. Eur HeartJ2000;21:1487-9. 17 Grines CL, Westerhausen DR, Grines LL, Hanlon JT, Logemann TL, Niemela M, et al, on behalfof the Air PAMI Study Group. A randomized trial oftransfer for primary angioplasty versus on-site thrombolysis in patients with high-risk myocardial infarction: The air primary angioplasty in myocardial infarction study. JAm Coll Cardiol 2002;39:1713-9. 18 Andersen HR, Nielsen T1, Rasmussen K, Thuesen L, Kelbaek H, Thayssen P, et al; DANAMI-2 Investigators. A comparison of coronary angioplasty with fibrinolytic therapy in acute myocardial infarction. NEnglJMed2003;349:733-42. 19 Cannon CP, Gibson CM, Lambrew CT, Shoultz DA, Levy D, French WJ, et al. Relationship ofsymptom-onset-to-balloon time and door-to-balloon time with mortality in patients undergoing angioplasty for acute myocardial infarction. JAMA 2000;283: 2941-7. 20 Verheugt FWA, Liem A, Zijlstra F, Marsh RC, Veen G, Bronzwaer JGF. High dose bolus heparin as initial therapy before primary angioplasty for acute myocardial infarction: results of the heparin in early patency (HEAP) pilot study. JAm Coil Cardiol 1998;31: 289-93. 21 Liem A, Zijlstra F, Ottervanger JP, Hoorntje JC, Suryapranata H, Boer MJ de, et al. High dose heparin as pretreatment for primary angioplasty in acute myocardial infarction: the Heparin in Early Patency (HEAP) randomized trial. JAm Coll Cardiol 2000;35: 600-4. 22 Zijlstra F, Ernst N, Boer MJ de, Nibbering E, Suryapranata H, Hoorntje JCA, et al. Influence of prehospital administration of aspirin and heparin on initial patency ofthe infarct-related artery in patients with acute ST elevation myocardial infarction. JAm Coll
Cardiol2002;39:1733-7. 23 Blankenship JC, Almquist AK Cardiovascular complications of thrombolytic therapy in patients with a mistaken diagnosis of acute myocardial infarction. JAm Coll Cardiol 1989;14:1579-82. 24 Granger CB, CaliffRM, Topol EJ. Thrombolytic therapy for acute myocardial infarction. A review. Drugs 1992;44:293-325. 25 The GUSTO Angiographic Investigators. The effects of tissue plasminogen activator, streptokinase, or both on coronary artery patency, ventricular function, and survival, after acute myocardial infarction. NEngljMed 1993;329:1615-22. 26 Boer MJ de, Zijlstra F. Treating myocardial infarction in the postGUSTO Era. Pharmacoeconomics 1997;12: 427-37. 27 Zijlstra F, HofAWJ van 't, Liem AL, Hoorntje JCA, Suryapranata H, Boer MJ de. Transferring patients for primary angioplasty: a retrospective analysis of 104 selected high risk patients with acute myocardial infarction. Heart 1997;78:333-6. 28 Bonnefoy E, Lapostolle F, Leizorovicz A, Steg G, McFadden EP, Dubien PY, et al. Comparison of Angioplasty and Prehospital Thrombolysis in Acute Myocardial Infarction study group (CAPTIM). Primary angioplasty versus prehospital fibrinolysis in acute myocardial infarction: a randomised study. Lancet 2002;
360:825-9. 29 Montalescot G, Barragan P, Wittenberg 0, Ecollan P, Elhadad S, Villain P, et al, for the ADMIRAL investigators. N Engl JMed
2001;344:1895-903.
Ned Tijdschr Geneeskd 2001;145:2029-35.
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Netherlands Heart Journal, Volume 12, Number 4, April 2004
Prehospital triage for angiography-gu ided
therapy for acute myocardial infarction
N.M.S.KJ. Ernst, M.J. de Boer, A.W.J van 't Hof, F. Hollak, H. van de Wetering, J.H.E. Dambrink, J.C.A. Hoornje, H. Suryapranata, F. Zijlstra
Background. Time between symptom onset and effective reperfusion is of paramount importance in patients with acute myocardial infarction (MI) treated with reperfusion therapy. In the PHIAT (Pre-Hospital Infarction Angioplasty Triage) project, safety and feasibility of in-ambulance electrocardiography facilities for prehospital triage for direct transfer to an interventional centre to undergo immediate coronary angiography and angiography-guided therapy were evaluated. Methods and results. The ambulances were equipped with a defibrillator and electrocardiography unit with computerised electrocardiographic analysis. Patients with acute MI symptoms and fulfilling certain criteria compatible with a large MI were induded and pretreated with heparin and aspirin during transportation. During the study period, 284 patients were included. Eleven percent did not have an acute MI. PCI, performed in 94% (n=239) ofthe patients, was successful in 94%. Prehospital triage reduced time to treatment. In 32% of the patients triage resulted in direct transportation to the interventional centre instead of to the nearest community hospital. All-cause mortality was 9% after a mean follow-up of nine months. No serious bleeding complications were seen.
N.M.S.K.J. Emst M.J. de Boer A.W.J. van 't Hof J.H.E. Dambrlnk J.C.A. Hoomtje H. Suryapranata F. Zljilstra Isala Clinics, De Weezenlanden Hospital, Department of Cardiology, Groot Wezenland 20, 8011 JWZwolle F. Hollak H. van de Weterlng Regional Ambulance Service IJssel-Vecht B. V. Zwolle
Correspondence to: M.J. de Boer E-mail: [email protected]
Netherlands Heart Journal, Volume 12, Number 4, April 2004
Conclusion. Prehospital triage in the ambulance is safe and feasible. A stiking percentage (11%) ofthe identified patients does not have an acute MI and this is more than has been reported from prehospital thrombolysis trials. (Neth Heart J 2004;12:151-6.) Key words: myocardial infarction, prehospital triage, primary angioplasty
the time between onset of symptoms and achievement of complete reperfusion is of paramount importance for survival and recovery of left ventricular function after thrombolytic therapy for acute myocardial infarction."l2 A similar relation has also been demonstrated for reperfusion therapy by means of primary coronary angioplasty,3'7 although the outcome with regard to mortality seems less time-dependent in patients treated with primary angioplasty compared with patients treated with thrombolysis.8'9 In 1993, the first randomised trials comparing immediate coronary angioplasty with thrombolytic therapy in acute myocardial infarction reported a better clinical outcome with an immediate coronary angioplasty strategy.3'4 Compared with thrombolytic therapy, primary coronary angioplasty may be regarded as a better reperfusion therapy as it is associated with lower early and late mortality, a lower rate ofnonfatal reinfarction, fewer readmissions for recurrent ischaemia or heart failure and lower total medical costs. These benefits were sustained at longterm follow-up.'0 An advantage ofthrombolytic therapy is that it can already be started in the prehospital setting by general practitioners and paramedical ambulance staff, which may result in a reduction in time from onset of symptoms to start of reperfusion therapy."'1-3 Contrary to lytic therapy, a disadvantage of primary coronary angioplasty is that it can only be performed in a limited number of specialised centres. Patients presenting to a centre without coronary angioplasty facilities may therefore need immediate additional transfer to such 151
Prehospital triage for angiography-guided therapy for acute myocardial infarction
WPW or LBBB or IV-conduction block or pacemaker rhythm H
yes
No
>0.2 mV ST elevation in >2 leads V1-V6 and >0.3 mV ST elevation in >1 lead Vi-V6 Yes
Sum of ST elevation in V1-V6 plus Sum of ST depression in 11, 111, aVF .0.8
I~~~~~~~~~~ V
zICz
mV
No
A Yes
.0.1 mV ST elevation in .2 leads 11, 111, aVF and .0.2 mV ST elevation in .1 lead 11, Ill, aVF
No PTCA
0
-No
I
I Yes
Sum of ST elevation in 1-111, aVF plus Sum of ST depression in V1-V4 .0.6 mV
No
Figure 1. ECG algorithm used in the PHIAT (Pre-Hospital Infarction Angioplasty Triage) project. a specialised centre. This results in an extra time delay before reperfusion therapy can be delivered. We introduced in-ambulance electrocardiography and analysis facilities for prehospital triage for direct transfer to our hospital for patients with acute myocardial infarction to undergo immediate coronary angiography and subsequent angiography-guided therapy. This study evaluated the safety and feasibility of this ambulance triage project.
152
Methods In the PHIAT (Pre-Hospital Infarction Angioplasty Triage) project, initially six and finally all 15 ambulances in the Zwolle region were equipped with a defibrillator and electrocardiography unit (Corpuls-Schiller) with
computerised electrocardiographic (ECG) analysis using the algorithm depicted in figure 1. Two ambulances from a neighbouring region (at a mean distance of 30 kilometres from our hospital) also took part in the registry.
Netherlands Heart Joumal, Volume 12, Number 4, April 2004
Prehospital triage for angiography-guided therapy for acute myocardial infarction
Patients with symptoms of an acute myocardial infarction for at least 30 minutes and fulfilling the criteria from the computer algorithm were included. Patients having symptoms for more than 24 hours at presentation and patients older than 80 years were excluded. Contraindications for thrombolytic therapy, previous myocardial infarction or bypass surgery were not reasons to exclude patients from the registry. All ambulance personnel completed a training programme to carry out high-quality ECGs. If the ECG analysis by the automated algorithm fulfilled the positive identification criteria as shown in figure 1, an immediate call to the central ambulance unit was followed by administration of 10,000 IU heparin and 500 mg aspirin intravenously and A-I (very urgent) transport to our hospital. The central ambulance unit communicated the expected time of arrival to our hospital to allow preparation ofthe coronary care unit, the catheterisation laboratory, auxiliary personnel and the interventional cardiologist on call. Data on time intervals, patient characteristics and clinical outcome were registered in a dedicated database. An acute myocardial infarction was defined as the presence of a positive ECG combined with an unstable coronary lesion at acute angiography and/or the presence of enzymatic myocardial damage, defined as an increase in creatinine kinase of at least two times the upper limit ofnormal. Transportation distances were calculated using postal codes from the locations where the diagnosis of the acute myocardial infarction was made and postal codes from the various hospitals. TIMI flow grade and the degree of residual stenosis were visually assessed by the interventional cardiologist as well as by the angiographic core laboratory. Success of the primary PCI was defined as the presence of TIMI flow grade 3 after the procedure and a residual stenosis of less than 50%. Left ventricular ejection fraction was measured in our nuclear laboratory using a technique with Technetium-labelled red blood cells, as previously described.3'5"0 Results
Clinical characteristics From 15 November 1998 to 31 December 2000,284 patients fulfilled the PHIAT criteria for acute myocardial infarction. One patient died before arrival in the hospital (autopsy was not performed, cause of death unknown). Clinical characteristics of the remaining 283 patients are shown in table 1. The mean age ofthe patients was 62±12 years (range 16 to 83 years). Twenty-three patients (8%) of the total group of 284 patients did not have angiographic confirmation of acute myocardial infarction and the absence of acute myocardial infarction was confirmed by repeated enzyme measurements. In seven patients (2.5%) no coronary angiography was performed, because the
Netherlands Heart Journal, Volume 12, Number 4, April 2004
Table 1. Clinical characteristics of 283 patients who fulfilled PHIAT criteria.
Male Hypertension Diabetes mellitus Smoking Hypercholesterolaemia Family history CAD Previous myocardial infarction Previous PCI Previous CABG Previous stroke Killip class I at admission Killip class II at admission Killip class Ill at admission Killip class IV at admission
n
%
211 87 34 141 56 117 33 14 14 12 253 10 16 4
74 31 12 50 20 41 12 5 5 4 89 4 6 1
CAD=coronary artery disease, PCI=percutaneous transluminal coronary angioplasty, CABG=coronary artery bypass grafts.
Table 2. Diagnoses of 'false-positive' patients who fulfilled PHIAT criteria.
Pericarditis
Supraventricular arrhythmia Atypical chest pain/early repolarisation on electrocardiogram No signs of coronary artery disease on acute angiography Presence of coronary artery disease on acute angiography, no unstable lesion Aortic valve stenosis, left ventricular hypertrophy Myocarditis/congestive heart failure Total
n
%
1 2
3 7
4
13
2
7
15
50
4 2 30
13 7 100
patient's clinical condition on admission and repeated electrocardiography and enzyme measurements confirned the absence of an acute myocardial infarction. Definitive clinical diagnoses ofthese 30 'false-positive' patients are shown in table 2. From the remaining 254 patients with a confirmed diagnosis of an acute myocardial infarction, 46% suffered from an anterior wall myocardial infarction. Treatment From the group of 254 patients with an acute myocardial infarction 251 patients (99%) underwent immediate coronary angiography (i.e. immediately after admission); from the remaining three patients, in153
Prehospital triage for angiography-guided therapy for acute myocardial infarction
at-100
-100
-
= 1.
c7
95f
=
90-
x
-L
=
90 en
2
4
6
8
10
12 Months
Figure 2. Kaplan-Meier curve for all-cause mortality from 284 patients who fulfilled the PHIATcriteria.
cluding the one who died in the ambulance before arrival in the hospital, one patient was known to have extensive three-vessel coronary artery disease, not amenable to percutaneous or surgical intervention, and one patient suffered from an acute myocardial infarction due to atrial fibrillation with a rapid ventricular response and a severe aortic stenosis. In this patient coronary angiography was performed at a later stage as prelude to cardiac surgery. From the group of patients with a confirmed diagnosis of an acute myocardial infarction, 239 patients (94%) were treated with primary coronary intervention (PCI). Bypass surgery was performed during the initial admission in five patients (2%). Eight patients (3%) were treated conservatively (i.e. no primary PCI or bypass surgery). Time intervals The mean door-to-balloon time for the patients treated with primary PCI was 43 minutes (25th percentile 27 minutes, median 39 minutes, 75th percentile 50 minutes). From the group of 254 patients with an acute myocardial infarction, 214 patients (84%) had symptoms for less than six hours before admission. The mean duration from start of symptoms to admission was 140 minutes, and the mean total ischaemic time, defined as time from symptom onset to first balloon inflation, was 183 minutes.
Angiographic and clinical outcome At acute coronary angiography the following TIMI flow grades of the infarct-related vessel pre-PCI were seen: TIMI flow grade 0 in 129 patients (5 1%), TIMI flow grade 1 in 24 patients (10%), TIMI flow grade 2 in 38 patients (15%) and TIMI flow grade 3 was seen in 60 patients (24%). The primary PCI procedure was successfuil in 224 patients (94%). In 207 patients (8 1%) nuclear ejection fraction was measured within three 154
80 ; ,
6
12 Months
Figure 3. Kaplan-Meier curve for surpival without reinfarction for 284 patients who fulfilled the PHMATcriteria.
days after admission. The mean ejection fraction was 45% (range 17 to 70%). With respect to all-cause mortality of all patients who fuffilled the ambulance criteria the following was seen: 16 patients (6%) died during first admission (inhospital mortality) and, as already mentioned, one patient died before admission. With a mean follow-up of one year, 25 patients (9%) died (figure 2). The Kaplan-Meier curve for survival without the occurrence of reinfarction is shown in figure 3. All 284 patients who fulfilled the ambulance criteria for acute myocardial infarction were given heparin and aspirin intravenously in the ambulance during transportation. No bleeding complications (including stroke) were seen in any of the patients in the prehospital phase. None of the patients experienced a serious bleeding complication during admission until the acute coronary angiography and primary PCI.
Discussion Data from this PHIAT project show that ambulance personnel are capable of diagnosing acute ST-elevation myocardial infarction in almost 90% of patients by doing an electrocardiogram in the prehospital phase. Using the PHIAT protocol, after equipping and training of ambulance personnel, patients with large myocardial infarctions (i.e. large cumulative STsegment deviation) can be referred directly and safely to an interventional centre. A striking percentage of the patients (11%) who fulfilled the PHIAT criteria did not have angiographic confirmation of an acute myocardial infarction and the absence of an acute myocardial infarction in these patients was confirmed by repeated enzyme tests. This is a higher percentage than has been reported from
prehospital thrombolysis trials.13'15 The total ischaemic time of patients with acute myocardial infarction treated with primary coronary Netherlands Heart Journal, Volume 12, Number 4, April 2004
Prehospital triage for angiography-guided therapy for acute myocardial infarction
angioplasty is a combination ofpatient delay, response delay of the primary care system, transportation delay, and the time needed to establish reperfusion in the catheterisation laboratory.'6 Prehospital triage is associated with a reduction in total ischaemic time compared with patients seen primarily in the emergency room or referred from one of the surrounding community hospitals without interventional facilities.'6 If no prehospital triage were performed, 82 patients (32%) with an acute myocardial infarction would initially have been admitted to the nearest community hospital without interventional facilities leading to an additional delay in the local emergency room and during subsequent transportation to our hospital. If these patients had been referred to our hospital via the nearest community hospital the transportation distance would have increased from an actual distance of 32±9 kilometres to a distance of 51±11 kilometres. The extra (mean) transportation distance of 19 kilometres plus the mean in-door-out-door-time at the noninvasive centre, which is about 45 minutes as is known from Air Primary Angioplasty in Myocardial Infarction (AirPAMI) and the DANish trial in Acute Myocardial Infarction (DANAMI-2) studies,'7"18 therefore results in a mean gain of at least 60 minutes. This time must be added to the extra time gained due to making prehospital infarct diagnosis leading to a reduction in door-to-balloon-time. Data from the National Registry of Myocardial Infarction (NRMI-2 registry) of more than 27,000 patients from 661 hospitals in the United States clearly showed the relationship between increased mortality and delay in door-to-balloon time,'9 especially when door-to-balloon time is greater than 120 minutes. Door-to-balloon time was longer than two hours in nearly 50% of the patients in this cohort. In our data the mean door-to-balloon time was only 43 minutes due to preparation of staff starting after announcement of the patient's time of arrival by the ambulance service. Although it was shown in DANAMI-2 that with a transportation time of three hours to an interventional centre primary PCI is still superior to in-hospital thrombolysis in a noninterventional centre, time gain remains of paramount importance. According to the observed high patency rate of the infarct-related vessel at acute angiography before primary PCI, it can be concluded that this prehospital reperfusion had occurred in more patients than was anticipated. The role of the administration of intravenous heparin pre-PCI with respect to this issue showed conflicting results in previous observations.20'2' However, recently it was shown that prehospital administration of heparin and aspirin resulted in a higher initial patency of the infarct-related artery in patients with acute myocardial infarction.22 As data on left ventricular ejection fraction are not complete, no reliable conclusions on the preservation of the left ventricular function or the relation with the initial patency can be made. Netherlands Heart Journal, Volume 12, Number 4, April 2004
Although the all-cause mortality seems relatively high, it should be considered that only patients with large acute myocardial infarction, of whom 46% were suffering from an anterior myocardial infarction (i.e. selection of high-risk population), were included in the PHIAT project. Only one patient died in the prehospital phase. Furthermore, patients with Killip class III and IV were not excluded from study entry, and neither were elderly people up to 80 years. Thrombolytic therapy is still restricted for selected patients filfilling strict inclusion criteria and leads to more bleeding complications, a modest reperfusion rate and a worse clinical outcome compared with primary coronary angioplasty.8l2,23 26 As our data show, the intravenous administration of heparin and aspirin in the ambulance did not lead to any (major) bleeding complication whereas contraindications for thrombolytic therapy were no reason to exclude patients. The logistics and clinical problems regarding referral of patients for primary coronary angioplasty from hospitals without interventional facilities have been described before.27
Several issues remain to be studied further: the comparison of prehospital thrombolysis with prehospital triage guided primary coronary angioplasty and the effect of primary coronary angioplasty facilitated with early treatment with specific agents such as thrombolytic agents and/or glycoprotein IIb/IIIa receptor blockers. The first trial to compare prehospital thrombolysis with primary coronary angioplasty in patients with acute myocardial infarction recently showed inconclusive results.28 The Comparison ofAngioplasty and Prehospital Thrombolysis In acute Myocardial infarction (CAPTIM) Investigators reported that patients who received prehospital thrombolysis showed a trend towards more reinfarctions but fewer deaths compared with the patients treated with primary angioplasty. The Abciximab before Direct angioplasty and stenting in Myocardial Infarction Regarding Acute and Long-term follow-up (ADMIRAL) trial strongly suggests a positive effect of glycoprotein IIb/IIIa receptor blockers, only when they are administered before arrival in the hospital.29 Conclusions Prehospital triage in the ambulance for patients with acute myocardial infarction is a safe, effective and feasible way to identify patients who are candidates for primary coronary angioplasty, and leads to an important reduction in ischaemic time. Eleven percent of the identified patients do not have an acute myocardial infarction. Further attention needs to focus on this high number of patients without a confirmed diagnosis of acute myocardial infarction, in particular as unnecessary treatment may be harmful. i
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Acknowledgements The authors would like to thank Mrs Vera Derks for her excellent secretarial assistance in preparing the manuscript. References Simoons ML, Serruys PW, Brand M van den, Res J, Verheugt FWA, Krauss XH, et al. Early thrombolysis in acute myocardial infarction: Limitation ofinfarct size and improved survival. JAm Coll Cardiol 1986;7:717-28. 2 Boersma E, Maas ACP, Deckers JW, Simoons ML. Early thrombolytic treatment in acute myocardial infarction: reappraisal of the golden hour. Lancet 1996;348:771-5. 3 Zijlstra F, Boer MJ de, Hoorntje JCA, Reiffers S, Reiber JHC, Suryapranata H. A comparison ofimmediate coronary angioplasty with intravenous streptokinase in acute myocardial infarction. N EnglJMed 1993;328:680-4. 4 Grines CL, Browne KF, Marco J, Rothbaum D, Stone GW, O'Keefe J, et al for the Primary Angioplasty in Myocardial Infarction Study group. A comparison of immediate angioplasty with thrombolytic therapy for acute myocardial infarction. NEn,glJMed 1993;328:673-9. 5 Boer MJ de, Suryapranata H, Hoorntje JCA, Reiffers S, Liem AL, Miedema K, et al. Limitation of infarct size and preservation of left ventricular function after primary coronary angioplasty compared with intravenous streptokinase in acute myocardial infarction. Circulation 1994;90:753-61. 6 O'Neill WW, Boer MJ de, Gibbons RJ, Holmes DR, Timmis GC, Sachs D, et al. Lessons from the pooled outcome of the PAMI, Zwolle and Mayo clinic randomized trials of primary angioplasty versus thrombolytic therapy of acute myocardial infarction. J Invasive Cardiol 1998;10:4-10. 7 Berger PB, Ellis SG, Holmes DR, Granger CB, Criger DA, Betriu A, et al, for the GUSTO-II investigators. Relationship between delay in performing direct coronary angioplasty and early clinical outcome in patients with acute myocardial infarction. Results from the Global Use of STrategies to open Occluded arteries in acute coronary syndromes (GUSTO-IIb) trial. Circulation 1999;100: 14-20. 8 Zijlstra F, Patel A, Jones M, Grines CL, Ellis S, Garcia E, et al, for the PCAT collaboration. Clinical characteristics and outcome of patients with early (4h) presentation treated by primary coronary angioplasty or thrombolytic therapy for acute myocardial infarction. EurHeartJ2002; 23:5507. 9 Bertrand ME, McFadden EP. Late is perhaps not... too late for primary PCI in acute myocardial infarction. EurHeartJ2002;23: 1146-8. 10 Zijlstra F, Hoorntje JCA, Boer MJ de, Reiffers S, Miedema K, Ottervanger JP, et al. Long-term benefit of primary angioplasty as compared with thrombolytic therapy for acute myocardial infarction. NEnglJMed 1999;341:1413-9. 11 Rawles JM. Quantification of the benefit of earlier thrombolytic therapy: five-year results ofthe Grampian Region EarlyAnistreplase Trial (GREAT). JAm Coll Cardiol 1997;30:1181-6. 12 Leizorovicz A, Haugh MC, Mercier C, Boissel JP. Pre-hospital and hospital time delays in thrombolytic treatment in patients with suspected acute myocardial infarction. Analysis of data from the EMIP study. European Myocardial Infarction Project. Eur Heart 1
J1997;18:248-53. 13 Boersma E, Maas AC, Hartman JA, Ilmer B, Vos J, Simoons ML. Twelve year triage and thrombolysis treatment prior to hospitalization for myocardial infarction patients in the Rotterdam area ofthe Netherlands: outstanding short-term and long-term results.
14 O'Rourke MF, Cook A, Carroll G, Gallagher D, Hall J. Accuracy of a portable interpretive ECG machine in diagnosis of acute evolving myocardial infarction. Aust NZJMed 1992;22:9-13. 15 Grijseels EWM, Bouten MJM, Lenderink T, Deckers JW, Hoes AW, Hartman JAM, et al. Pre-hospital thrombolytic therapy with either alteplase or streptokinase. Practical applications, complications and long-term results in 529 patients. Eur Heartj 1995; 16:1833-8. 16 Zijlstra F. Long-term benefit ofprimary coronary angioplasty compared to thrombolytic therapy for acute myocardial infarction. Eur HeartJ2000;21:1487-9. 17 Grines CL, Westerhausen DR, Grines LL, Hanlon JT, Logemann TL, Niemela M, et al, on behalfof the Air PAMI Study Group. A randomized trial oftransfer for primary angioplasty versus on-site thrombolysis in patients with high-risk myocardial infarction: The air primary angioplasty in myocardial infarction study. JAm Coll Cardiol 2002;39:1713-9. 18 Andersen HR, Nielsen T1, Rasmussen K, Thuesen L, Kelbaek H, Thayssen P, et al; DANAMI-2 Investigators. A comparison of coronary angioplasty with fibrinolytic therapy in acute myocardial infarction. NEnglJMed2003;349:733-42. 19 Cannon CP, Gibson CM, Lambrew CT, Shoultz DA, Levy D, French WJ, et al. Relationship ofsymptom-onset-to-balloon time and door-to-balloon time with mortality in patients undergoing angioplasty for acute myocardial infarction. JAMA 2000;283: 2941-7. 20 Verheugt FWA, Liem A, Zijlstra F, Marsh RC, Veen G, Bronzwaer JGF. High dose bolus heparin as initial therapy before primary angioplasty for acute myocardial infarction: results of the heparin in early patency (HEAP) pilot study. JAm Coil Cardiol 1998;31: 289-93. 21 Liem A, Zijlstra F, Ottervanger JP, Hoorntje JC, Suryapranata H, Boer MJ de, et al. High dose heparin as pretreatment for primary angioplasty in acute myocardial infarction: the Heparin in Early Patency (HEAP) randomized trial. JAm Coll Cardiol 2000;35: 600-4. 22 Zijlstra F, Ernst N, Boer MJ de, Nibbering E, Suryapranata H, Hoorntje JCA, et al. Influence of prehospital administration of aspirin and heparin on initial patency ofthe infarct-related artery in patients with acute ST elevation myocardial infarction. JAm Coll
Cardiol2002;39:1733-7. 23 Blankenship JC, Almquist AK Cardiovascular complications of thrombolytic therapy in patients with a mistaken diagnosis of acute myocardial infarction. JAm Coll Cardiol 1989;14:1579-82. 24 Granger CB, CaliffRM, Topol EJ. Thrombolytic therapy for acute myocardial infarction. A review. Drugs 1992;44:293-325. 25 The GUSTO Angiographic Investigators. The effects of tissue plasminogen activator, streptokinase, or both on coronary artery patency, ventricular function, and survival, after acute myocardial infarction. NEngljMed 1993;329:1615-22. 26 Boer MJ de, Zijlstra F. Treating myocardial infarction in the postGUSTO Era. Pharmacoeconomics 1997;12: 427-37. 27 Zijlstra F, HofAWJ van 't, Liem AL, Hoorntje JCA, Suryapranata H, Boer MJ de. Transferring patients for primary angioplasty: a retrospective analysis of 104 selected high risk patients with acute myocardial infarction. Heart 1997;78:333-6. 28 Bonnefoy E, Lapostolle F, Leizorovicz A, Steg G, McFadden EP, Dubien PY, et al. Comparison of Angioplasty and Prehospital Thrombolysis in Acute Myocardial Infarction study group (CAPTIM). Primary angioplasty versus prehospital fibrinolysis in acute myocardial infarction: a randomised study. Lancet 2002;
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