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Prehospital Therapy With the Platelet
Glycoprotein IIb/IIIa Inhibitor
Eptifibatide in Patients With Suspected
Acute Coronary Syndromes*

The Bochum Feasibility Study
Christoph Hanefeld, MD; Clemens Sirtl, MD; Martin Spiecker, MD;Waldemar Bojara, MD; Peter H. Grewe, MD; Thomas Lawo, MD; andAndreas Mu¨gge, MD Study objectives: To assess the practical application and safety of prehospital antithrombotic
therapy with the glycoprotein (GP) IIb/IIIa inhibitor eptifibatide for patients with suspected
acute coronary syndrome (ACS) or myocardial infarction (MI).
Design:
Open-labeled pilot study. Patients with typical chest pain who were seen within 6 h of the
onset of symptoms were enrolled in the mobile emergency ambulance. Patients were stratified by
even/uneven days to receive standard treatment or standard treatment plus an IV bolus of
eptifibatide (180
g/kg body weight) followed by a continuous eptifibatide infusion (2 g/kg/min).
The main outcome measurement was a combination of prehospital or in-hospital death,
reinfarction, revascularization of target vessels, and major bleeding complications.
Results:
A total of 356 patients (age range, 29 to 75 years; women, 24.7%) were included in the
analysis. On admission to the hospital, the diagnosis of ACS or MI was confirmed in approximately
60% of patients, and alternative diagnoses were made in 40% of patients. The rates of
complications, including fatal and nonfatal complications occurring during transportation and
during subsequent hospitalization, were similar in both study groups. The primary end point
occurred in 11.8% of patients in the control group, and in 9.6% of those in the eptifibatide group
(difference not significant).
Conclusion:
The prehospital administration of the GP IIb/IIIa inhibitor eptifibatide is feasible
and safe in patients with clinically suspected ACS and MI. The benefit of this treatment has yet
to be established in a large-scale multicenter study.

(CHEST 2004; 126:935–941)
Key words: acute coronary syndrome; eptifibatide; glycoprotein IIb/IIIa inhibitor; myocardial infarction; primary
percutaneous coronary intervention
Abbreviations: ACS ϭ acute coronary syndrome; CAD ϭ coronary artery disease; CK ϭ creatinine kinase;
GP ϭ glycoprotein inhibitor; MI ϭ myocardial infarction; NSTEMI ϭ non-ST-segment elevation myocardial infarction; PCI ϭ percutaneous coronary intervention; STEMI ϭ ST-segment elevation myocardial infarction; TIMI ϭ thrombol- ysis in myocardial infarction; UA ϭ unstable angina Acute coronary syndromes (ACSs) are character- riding principles for treatment of patients with
ized by an imbalance between myocardial oxygen STEMI and ACS are the achievement of infarct- supply and demand, which is commonly caused by a related artery patency and ruptured plaque stabili- reduced coronary blood flow. Unstable angina (UA) zation.1,2 Keeping the time delay between the onset is differentiated from non-ST-elevation myocardial of symptoms and the initiation of an adequate ther- infarction (NSTEMI) and ST-elevation myocardial apy as short as possible is equally important.
infarction (STEMI) according to the release of bio- Until now, the strategies for reducing time delays chemical markers of myocardial necrosis and/or ST- have mainly focused on prehospital management.3 segment elevations seen in the surface ECG.1,2 This Prehospital management encompasses community differentiation is part of an evidence-based risk planning, public awareness, prehospital diagnosis, stratification that is used to target more aggressive and prehospital therapy.3 All of these factors are antithrombotic and interventional therapies in pa- aimed at facilitating and accelerating diagnostic pro- tients presenting with ACS and STEMI. The over- cedures and therapeutic consequences once the hospital is reached.4 Several trials3,4 have addressed in high-risk patients undergoing PCI.5,6 This form of the safety and usefulness of prehospital thrombolysis therapy is being used increasingly as the primary in patients with STEMI, and have shown reductions treatment in patients presenting with ACS and in both time to treatment and in mortality, especially STEMI.8 A third rationale, derived from past expe- in rural areas. No specific prehospital management riences, was that a definitive diagnosis of ACS, and plan has yet been defined for patients with ACS.
frequently of MI as well, is difficult or even impos- These patients are admitted to hospital emergency sible to achieve in the setting of mobile emergency departments more frequently than are patients with ambulances.9 The potential side effects of GP IIb/ IIIa inhibitors under these circumstances appear to Guidelines1,2 for the in-hospital management of be tenable in patients with suspected but not proven patients with ACS and STEMI have addressed the superior role of early percutaneous coronary inter-ventions (PCIs), particularly in combination with glycoprotein (GP) IIb/IIIa inhibitors. In the Abcix-imab Before Direct Angioplasty and Stenting in Myocardial Infarction Regarding Acute and Long-term Follow-up trial,5 the additional application of Patients were enrolled into the study by emergency medical the GP IIb/IIIa inhibitor abciximab before acute personnel outside the hospital setting. Patients with pain that wascharacteristic of MI/ACS who were seen within 6 h of the onset PCI/stenting in patients with STEMI already had of symptoms were eligible for inclusion in the study. Patients improved coronary patency prior to stenting, the were excluded if they were Ͻ 18 years of age or Ͼ 75 years of success rate of the stenting procedure, as well as the age, if they were receiving oral phenpnocoumon (Marcumar; rate of coronary patency and clinical outcome at 6 CT-Arzneimittel; Berlin, Germany) treatment, if they wereknown to have a hemorrhagic diathesis, or if they had recently (ie, months. For patients with non-ST-elevation ACS, a Ͻ 4 weeks) received a diagnosis of active peptic ulcer disease, meta-analysis of randomized trials6 revealed a bene- had experienced a stroke, surgery or major trauma within the fit for early PCIs. The benefit was more pronounced preceding 3 months, if they were known or suspected to be if the procedure was performed while a GP IIb/IIIa pregnant, and if they declined to give their informal consent to participate. They also could be excluded from the study for otherreasons at the discretion of the emergency medical doctor.
In the present pilot study, we addressed the Prehospital treatment was started at a patient’s home or in the feasibility of prehospital antithrombotic treatment mobile ambulance unit. The decision to classify a patient’s for patients with suspected ACS and myocardial symptom as suspected ACS or MI was made by the emergency infarction (MI). For our purposes, we chose the GP medical doctor. Since at the time of this study the emergency IIb/IIIa inhibitor eptifibatide for antithrombotic ambulance vehicles were equipped only with a one-channel ECGrecording system, classification of ACS/MI could not be based treatment since it inhibits platelet aggregation most exclusively on ECG readings. As a general rule, the emergency consistently.7 A second rationale for the use of a GP ambulance team would transfer a patient to the nearest hospital, IIb/IIIa inhibitor was the fact that this type of but they could also transfer the patient to a hospital equipped comedication improves the success rate and outcome with a catheterization laboratory providing a 24-h on-call servicefor acute PCI. The average time taken to transfer a patient fromhome to the nearest hospital by ambulance was usually Ͻ 15 min.
*From the Department of Cardiology & Angiology (Drs.
The emergency doctors are recruited from the divisions of Hanefeld, Spiecker, Bojara, Grewe, Lawo, and Mu¨gge), St.
internal medicine, surgery, and anesthesiology.
Josef-Hospital/Berufsgenossenschaftliche Kliniken Bergmann-sheil, Bochum, Germany; the Department of Anaesthesiology Three mobile rescue ambulances covering Bochum City (pop- (Dr. Sirtl), St. Josef-Hospital, University Hospitals of the Ruhr- ulation, approximately 400,000) participated. Three hospitals were equipped with a cardiac catheterization laboratory. In two This pilot project was funded by ESSEX Pharma, Munich, of the hospitals, a 24-h on-call duty for acute PCI also existed.
Germany. As part of this funding, the mobile ambulances were The routine annual PCI volume of these two units exceeds 400 equipped with refrigerators and were supplied with eptifibatide.
and 700 interventions. The time period from home to treatment The data were collected and analyzed by independent investiga- with emergency PCI in patients with STEMI is Ͻ 60 min.
tors. The enrollment of the patients in this study was done byindependent emergency doctors. None of the authors has cur-rently or had previously any financial involvement in ESSEX Pharma.
Manuscript received November 24, 2003; revision accepted April Patients were enrolled in an open-labeled study that was conducted by the Department of Cardiology & Angiology at the Reproduction of this article is prohibited without written permis- Ruhr-University Bochum in cooperation with the Bochum City sion from the American College of Chest Physicians (e-mail: Fire Department, which is in charge of the mobile ambulances.
The study consisted of the following two parts: 0 to 3 months; and Correspondence to: Andreas Mu¨gge, MD, Medical Clinic II 4 to 15 months (ie, April 1, 2001 to June 30, 2002). During the (Cardiology & Angiology), St. Josef-Hospital/Berufsgenossen- first 3 months, only control patients receiving standard prehos- schaftliche Kliniken Bergmannsheil, University Hospitals of theRuhr-University, Gudrunstrasse 56, D-44791 Bochum, Germany; pital treatment in the mobile emergency units were enrolled. The first 3 months were used to establish a data collection procedure and to define the participating hospitals. During the following 12 characteristics). Continuous measurements are presented as the months, patients were stratified according to even and uneven mean with SD. The ␹2 test was used to evaluate associations calendar days, and received either standard treatment on even between nonordered categoric variables. For dichotomous vari- days (ie, the control group) or standard treatment plus eptifi- ables, the p value from the Fisher exact test result is provided in batide on uneven days (ie, the eptifibatide group). The protocol situations in which expected cell frequencies were too low to use was approved by the institutional review board at the Ruhr- the ␹2 test. The Wilcoxon rank sum test was used for ordered University Bochum. A patient’s informed consent was obtained in categoric and continuous variables. A p value of Ͻ 0.05 was the mobile emergency ambulance. A second consent was ob- considered to be statistically significant. The control patients tained from the patient by medical hospital staff a day after during the first 3 months and during the allocation period were hospital admission. The second written consent included a record of the patient’s statistical data.
The standard treatment for patients with suspected ACS/MI in the mobile emergency ambulance consisted of IV aspirin (500 mg; Aspisol; Bayer AG; Leverkusen Germany), oral nitrates, andfluids. Other medications (eg, heparin, sedatives, catecholamines, Prehospital Diagnosis, Therapy, and Complications and morphine) were administered by the emergency medicaldoctor as required. Eptifibatide was administered in addition to A total of 422 patients with suspected ACS/MI the standard treatment as an IV bolus (180 ␮g/kg body weight) were screened in this study. Fifty-one patients were followed by a continuous infusion (2 ␮g/kg/min). The three excluded from the study because they were Ͼ 75 emergency ambulances were equipped with a small refrigeratorto store eptifibatide at 8°C.
years of age (eptifibatide group, 19 patients; control On arrival at the hospital, hospital staff could start, continue, or group, 32 patients). Four patients were excluded stop treatment with eptifibatide, initiate thrombolysis, or transfer from the study because of known contraindications the patient for emergency PCI. We did not attempt to standard- for GP IIb/IIIa inhibitors (current phenpnocouman ize prehospital or hospital care beyond common practice, there- treatment, three patients; known angiodysplasia, one fore, the care provided remained fully representative of thelocally established treatment plans.
patient). Eleven patients were excluded from the In order to define STEMI and ACS according to the Braun- analysis because of missing data (eptifibatide group, wald classification, and to actualize the treatment strategies in 4 patients; control group, 7 patients). Table 1 sum- these patients, all emergency doctors, irrespective of their sub-specialty, were required to attend a 2-h training seminar at thebeginning of this study. The seminar, which was conducted by a Table 1—Demographic Data, Prehospital Diagnosis,
cardiologist, also placed emphasis on the benefit of treatment Therapy, and Complications*
with primary PCI in patients with troponin-positive ACS andSTEMI over that with conventional thrombolysis.
Data Collection, End Points, and Statistical Analysis Report forms from the emergency ambulance transfer as well as the patient’s hospital charts were analyzed. Data analysis included ECG readings and laboratory findings at the time of hospital admission, as well as diagnosis, therapy, bleeding com- plications, and outcome since the time of hospital admission.
Major bleeding was defined as intracerebral bleeding, a decrease in hemoglobin of Ͼ 3 g/dL, as well as a hemorrhage requiring surgery or transfusion. Since the normal ranges of laboratory parameters varied slightly between participating hospitals, the abnormal values reported in the present study are in accordance The primary end point of this pilot study was a combination of prehospital or in-hospital death, reinfarction, revascularization of the target vessels, and major bleeding complications. Reinfarc- tion was defined according to clinical symptoms and new ECG changes with a new elevation of serum creatinine kinase (CK) levels. Revascularization was defined as a repeat PCI procedure or coronary artery bypass grafting on the primary reperfused target vessel. The secondary end points were the baseline thrombolysis in myocardial infarction (TIMI) flow grade before the patient underwent emergency PCI, the peak CK-myocardial bound level, and the frequency of congestive heart failure/shock and major bleeding complications. The TIMI flow grade (ie, none, minimal, partial, or complete perfusion) was graded retro- spectively by two invasive cardiologists who were blinded to the The data evaluated in this study include categoric, ordered categoric, and continuous variables. Categoric variables are pre- *Values given as mean Ϯ SD or %, unless otherwise indicated. Values sented as frequencies (ie, as percentages of patients with the in parentheses are %. NS ϭ not significant.
marizes the demographic data as well as the prehos- before being admitted to the hospital (97.5%). In pital diagnosis and treatment for 356 patients who contrast, a new therapy with GP IIb/IIIa inhibitors were included in this analysis. Less than 50% of the was started in only 39.5% of the patients in the patients had a known history of coronary artery control group (p Ͻ 0.01) [Table 3].
disease (CAD) or diabetes mellitus. According to the Seventy-seven patients (95.1%) in the eptifibatide clinical presentation of the patients and the duration group and 101 patients (81.5%) in the control group of chest pain, the emergency doctors suspected underwent cardiac catheterization within 2 h of acute MI in about 40% of the patients enrolled, and hospital admission. The percentage of patients with UA in approximately 60%. The classification of ACS/STEMI undergoing coronary angiography was patients with suspected UA or MI was similar in both significantly higher in the eptifibatide group than in treatment groups. The incidence of cardiac compli- the control group (95.1% vs 81.5%, respectively; cations during emergency transfer to the hospital p Ͻ 0.01). The vast majority of patients underwent was low and did not differ between the two groups.
Hospital Diagnosis, Therapy, and Outcome Table 3—Hospital Therapy in Patients With
At the time of admission to the hospital, STEMI ACS/STEMI*
was diagnosed in 30.3% of the control group and in34.1% of the eptifibatide group (Table 2). An ACS (US/NSTEMI) was diagnosed in 25.8% of the con- trol group and in 25.9% of the eptifibatide. Approx-imately 60% of patients with ACS had a positive troponin (either I or T) test result. All in all, 81 patients (60%) who had been assigned to the eptifi- batide group and 124 patients (56.1%) in the control group had a definite diagnosis of ACS or STEMI. In the remaining patients, alternative diagnoses to ACS or STEMI were made in the hospital (Table 2). After excluding STEMI/ACS or establishing an alternative diagnosis, the infusion with eptifibatide was stopped Target vessel (judged from catheter study) Treatment with GP IIb/IIIa inhibitors was contin- ued in the vast majority of patients with STEMI or ACS who had started receiving eptifibatide therapy Table 2—Clinical Diagnosis After Hospital Admission*
*Values given as No. (%) or mean Ϯ SD, unless otherwise indicated.
CABG ϭ coronary artery bypass grafting; LAD ϭ left anterior de- scending artery; Cx ϭ circumflex artery; RCA ϭ right coronary ar- tery; LMCA ϭ left main stem, MB ϭ myocardial bound. See Table 1 for abbreviation not used in the text.
†For the control group, therapy with GP IIb/IIIa inhibitors was initiated. For the eptifibatide group, therapy with GP IIb/IIIa inhibitors could be continued, stopped, or changed.
‡Within 2 h after hospital admission.
§Successful reperfusion with a residual lumen narrowing of Ͻ 50% ࿣Identification of culprit lesion/TIMI flow grade not possible because several vessels were closed/severely diseased or only minor diseased According to the coronary angiogram findings, a dence of the primary composite end point was not culprit lesion could be identified in Ͼ 80% of the different between the groups (control group, 13.7%; patients in both the control group and the eptifi- eptifibatide group, 12.3%; p ϭ 0.77).
batide group (Table 3). The filling and clearance ofthe contrast medium (ie, TIMI flow) preceding anyintervention was on average more rapid in patients receiving eptifibatide (Table 3). However, while inthe hospital the peak CK-myocardial bound levels This pilot study suggests that prehospital therapy did not differ between the study groups (Table 3).
with the GP IIb/IIIa inhibitor eptifibatide is feasible Seven patients (3.2%) in the control group and and safe in emergency situations in which patients four patients (3.0%) in the eptifibatide group died are suspected of having an ACS or a STEMI.
while in the hospital (Table 4). Nonfatal complica- Treatment with eptifibatide prior to hospital admis- tions occurred in 22.6% of the control patients and in sion led to an increase in the number of diagnostic 17.8% of the patients in the eptifibatide group.
angiographies performed during the subsequent hos- Major bleeding complications were observed in both pital stay. GP IIb/IIIa therapy concomitant to acute groups with a comparable frequency. The occur- PCI was continued in almost all patients who had rence of the primary composite end point (a combi- been pretreated with eptifibatide in the ambulance, nation of prehospital and in-hospital death, reinfarc- whereas in the control group a much smaller number tion, repeat PCI/coronary artery bypass grafting of of patients started receiving treatment with GP the target vessel, and major bleeding complication) IIb/IIIa inhibitors. We gained the impression that showed no significant difference between the groups patients having received eptifibatide beforehand (control group, 11.8%; eptifibatide group, 9.6%; showed fewer coronary artery occlusions with TIMI p ϭ 0.53) [Table 4]. In a subgroup analysis consid- grade 0 or I blood flow during primary percutaneous ering only those patients who had ACS/STEMI, 5 of transluminal coronary angioplasty than those in the 124 patients (4.0%) in the control group and 3 of 81 control group. However, the survival rates as well as patients (3.7%) in the eptifibatide group died while the rates of other cardiac and noncardiac complica- in the hospital (difference not significant). The inci- Previous studies investigating prehospital treat- ment focused on patients with STEMI that had beendocumented by a 12-lead ECG in the ambulance Table 4 —In-Hospital Complications/Events*
and early thrombolysis. The European Myocardial Infarction Study,10 in which 163 study centers in 15 different countries enrolled Ͼ 5,400 patients, was the largest study of this kind. The study revealed a 13% reduction (p ϭ 0.08) in mortality among pa- tients in the thrombolysis group. The indication to administer a thrombolytic agent was based on changes documented in a 12-lead ECG taken in the ambulance. Retrospectively, the diagnosis of a STEMI was subsequently confirmed in hospital in 87.6% of the patients included in the study, whereas 7.5% of the cases turned out to be a NSTEMI. In only 3% of patients was there either no indication for thrombolysis or thrombolysis was contraindicated.
Unfortunately, any information regarding the per- centage of patients with NSTEMI or STEMI actu- ally being considered for prehospital thrombolysis in At present, there are no studies targeting the prehospital treatment of patients with ACS in addi- tion to patients with definite or highly probable STEMI. There are also no data available yet refer- ring to an experience with the prehospital applica-tion of GP IIb/IIIa inhibitors in the setting of *Values given as No. (%), unless otherwise indicated. CPR ϭ cardio- pulmonary rescucitation; NYHA ϭ New York Heart Association.
emergency medical care in an ambulance.
See Tables 1and 3 for abbreviations not used in the text.
Various factors already mentioned in the introduc- tion, as well as locally specific factors, prompted us to showing that concurrent treatment with GP IIb/IIIa initiate this pilot study of prehospital treatment with inhibitors can increase the benefit of PCI in patients eptifibatide in an ambulance. The mere clinical with ACS. The relatively small number of patients in suspicion of ACS or MI and the prehospital com- our pilot study allows no conclusions to be drawn mencement of eptifibatide therapy, regardless of regarding the clinical benefit of reducing infarct size diagnostic confirmation by ECG or cardiac enzyme serology made in the ambulance, sufficed for inclu- In summary, our pilot study confirms the feasibil- sion in the study. The aim of this approach was to ity of prehospital treatment with GP IIb/IIIa inhib- provide an opportunity to take a much broader range itors for patients with suspected ACS or STEMI.
of patients with suspected ACS into consideration.
There was no evidence of increased risks caused by Following admission to the hospital, the diagnosis this type of treatment. However, the significance of ACS/STEMI was confirmed in 60% of the cases and any clinical benefit can be evaluated only by a refuted in 40%. In the latter group of patients, alternative diagnoses were made in which eptifi-batide therapy was retrospectively not indicated or contraindicated in a few cases. There was no higherincidence of complications, particularly hemor- Alternate-day assignment is a deterministic rhages, seen in the eptifibatide group compared with method of allocation, but not an appropriate method patients in the control group. None of our patients of randomization, and it has relevant limitations.
experienced intracerebral bleeding as the most ad- Since group assignments can be predicted in ad- verse hemorrhagic event. Similarly, in the Platelet vance of assignment, participant allocation may be Glycoprotein IIb/IIIa in Unstable Angina: Receptor manipulated, causing selection bias. However, any Suppression Using Integrilin Therapy trial11 the risk randomization protocol is difficult to implement of hemorrhagic stroke in 6,209 patients who had under emergency conditions. Thus, our approach been treated with eptifibatide was Ͻ 0.1%, which was a practicable option for a best effort at random- was not different from that observed in the placebo Interestingly, pretreatment with eptifibatide led more frequently to treatment with GP IIb/IIIa in- hibitors concomitant with the performance of PCI 1 Braunwald E, Antman EM, Beasley JW, et al. ACC/AHA compared than in patients in the control group. It guidelines for the management of patients with unstable seems that hospital-based doctors are more inclined angina and non-ST-segment elevation myocardial infarction: to continue with a preexisting treatment plan than to executive summary and recommendations; a report of theAmerican College of Cardiology/American Heart Association commence a new one. The majority of patients with task force on practice guidelines (committee on the manage- troponin-positive ACS and STEMI underwent coro- ment of patients with unstable angina). Circulation 2000; nary angiography. The primary success rate of coro- nary interventions was almost identical in both study 2 Van de Werf F, Ardissino D, Betriu A, et al. Management of groups. Blinded analysis of coronary flow prior to acute myocardial infarction in patients presenting with ST-segment elevation. Eur Heart J 2003; 24:28 – 66 intervention revealed lower rates of TIMI blood flow 3 Cannon CP, Sayah AJ, Walls RM. Prehospital thrombolysis: grades of 0 and 1 in target vessels in patients in the an idea whose time has come. Clin Cardiol 1999; 22(suppl): eptifibatide group. These findings should be inter- preted very carefully, since neither the study design 4 Stern R, Arntz HR. Prehospital thrombolysis in acute myo- (ie, lack of randomization) nor the number of pa- cardial infarction. Eur J Emerg Med 1998; 5:471– 479 5 Montalescot G, Barragan P, Wittenberg O, et al. Platelet tients included in the study allows the drawing of glycoprotein IIb/IIIa inhibition with coronary stenting for significant conclusions. Our observations can at best acute myocardial infarction. N Engl J Med 2001; 344:1895– serve as an indicator that GP IIb/IIIa inhibitor therapy initiated in the prehospital setting and sub- 6 Roffi M, Chew DP, Mukherjee D, et al. Platelet glycoprotein sequently continued may potentially improve the IIb/IIIa inhibition in acute coronary syndromes. Eur Heart J2002; 23:1441–1448 initial condition of the patients before they undergo 7 Batchelor WB, Tolleson TR, Huang Y, et al. Randomized primary PCI. This observation is in agreement with a comparison of platelet inhibition with abciximab, tirofiban previous brief communication12 demonstrating that and eptifibatide during percutaneous coronary intervention in the emergency department administration of eptifi- acute coronary syndromes: the COMPARE trial. Circulation batide before angioplasty resulted in a significantly 8 Andersen HR, Nielsen TT, Rasmussen K, et al. A comparison higher incidence of partial or complete reperfusion of coronary angioplasty with fibrinolytic therapy in acute in 30 patients with acute MI. Furthermore, this myocardial infarction. N Engl J Med 2003; 349:733–742 observation is in line with that of a meta-analysis6 9 Kudenchuk PJ, Maynard C, Cobb LA, et al. Utility of the prehospital electrocardiogram in diagnosing a coronary syn- comes in the platelet glycoprotein IIb/IIIa in unstable angina; dromes: the Myocardial Infarction Triage and Intervention receptor suppression using integrilin therapy (PURSUIT) (MITI) project. J Am Coll Cardiol 1998; 32:17–27 10 European Myocardial Infarction Project Group. Prehospital 12 Cutlip DE, Cove CL, Irons D, et al. Emergency room thrombolytic therapy in patients with suspected acute myo- administration of eptifibatide before primary angioplasty for cardial infarction. N Engl J Med 1993; 329:383–389 ST elevation acute myocardial infarction and its effect on 11 Mahaffey KW, Harrington RA, Simoons ML, et al. Stroke in baseline coronary flow and procedure outcome. Am J Cardiol patients with acute coronary syndromes: incidence and out-

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