Persistence of Delays in Presentation and Treatment for Patients With Acute Myocardial Infarction: The GUSTO-I and GUSTO-III Experience

ORIGINAL CONTRIBUTION Persistence of Delays in Presentation and Treatment for Patients With Acute Myocardial Infarction: The GUSTO-I and GUSTO-III Experience From the Department of Emergency Medicine, University of Cincinnati, Cincinnati OH ; the Department of Medicine, University of Alberta, Edmonton, Alberta, Canada ; Duke Clinical Research Institute, Durham, NC ; Heart and Vascular Institute, Henry Ford Health System, Detroit, MI ll ; the Department of Medicine, University of Massachusetts Medical Center, Worcester, MA ; and the Cleveland Clinic Foundation, Cleveland, OH. # Author contributions are provided at the end of this article. Received for publication June 12, 2000. Revision received August 28, 2001. Accepted for publication October 30, 2001. Address for reprints: W. Brian Gibler, MD, University of Cincinnati College of Medicine, 231 Albert Sabin Way, Cincinnati, OH 45267-0769; 513-558-8086, fax 513-558-4599; E-mail brian.gibler@uc.edu. Copyright 2002 by the American College of Emergency Physicians. 0196-0644/2002/$35.00 + 0 47/1/121402 doi:10.1067/mem.2002.121402 W. Brian Gibler, MD Paul W. Armstrong, MD E. Magnus Ohman, MD W. Douglas Weaver, MD ll Amanda L. Stebbins, MS Joel M. Gore, MD L. Kristin Newby, MD Robert M. Califf, MD Eric J. Topol, MD # For the Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) Investigators See editorial, p. 164. Study objective: Early treatment with fibrinolytic therapy substantially decreases mortality in acute myocardial infarction (AMI). We examined delays to hospital arrival and treatment in 2 large, multinational, randomized trials of fibrinolytic therapy: Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO-I) and Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO- III). Methods: We evaluated delays to hospital arrival, time from arrival to treatment, and total time to treatment in the 27,849 US patients with AMI enrolled in GUSTO-I or GUSTO-III. Time intervals were defined prospectively for total time to treatment and symptom onset to hospital arrival as 0 to 2 hours (early), 2 to 4 hours, or more than 4 hours (late). Time to fibrinolytic therapy once inhospital was prospectively defined as 0 to 1 hour (early) or more than 1 hour (late). Socioeconomic data were also obtained from patients enrolled in the GUSTO-III trial. Results: In GUSTO-III, as in GUSTO-I, patients who arrived at the hospital later were older (64 years versus 60 years; P=.001) and more often female (35% versus 27%; P=.001), black (6% versus 4%; P=.02), and diabetic (25% versus 16%; P=.001). These groups also received treatment later once inhospital, as did patients with hypertension (48% versus 42%; P=.001), previous angina (46% versus 36%; P=.001), and previous infarction (21% versus 16%; P=.001). Higher levels of education, professional occupations, and private health insurance were associated with significantly earlier arrival and treatment. Although inhospital time to treatment has decreased (66 minutes to 48 minutes; P<.0001), time to arrival has not changed over the past 7 years, averaging 84 minutes. Conclusion: Certain groups of patients with AMI, including the elderly, women, diabetic patients, and minorities, exhibit delays to hospital arrival and treatment in the emergency set- FEBRUARY 2002 39:2 ANNALS OF EMERGENCY MEDICINE 123

ting. Patients with higher educational levels, professional occupations, and private health insurance arrive at the hospital sooner and receive treatment more quickly. Patients and health care providers must be educated regarding high-risk populations for delay to maximize benefit from fibrinolytic therapy. [Gibler WB, Armstrong PW, Ohman EM, Weaver WD, Stebbins AL, Gore JM, Newby LK, Califf RM, Topol EJ, for the Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) Investigators. Persistence of delays in presentation and treatment for patients with acute myocardial infarction: the GUSTO-I and GUSTO-III experience. Ann Emerg Med. February 2002;39:123-130.] INTRODUCTION A delay in receiving thrombolytic therapy for acute myocardial infarction (AMI) is associated with diminished treatment effect and increased mortality. 1 Although treatment administered up to 12 hours after symptom onset has proved beneficial, maximum benefit is achieved when therapy is provided within the first few hours. 2 Over the past decade, substantial public health efforts have successfully educated health care providers about the importance of timely treatment with thrombolytic therapy. 3 As a result, the time required to identify and treat patients with myocardial infarction in the emergency setting has been nearly halved. 4 Despite such success in decreasing time to treatment in the emergency department, no similar reduction in time from symptom onset to patient arrival at the hospital has been observed. In a study of all 41,021 patients enrolled in the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO-I) trial, certain patient groups arrived to the hospital late in the course of their AMI. 5 Female, elderly, diabetic, and hypertensive patients were found to be susceptible to delays in hospital arrival and treatment in the ED. We hypothesized that improvement in the inhospital time to treatment for US patients with AMI would be associated with a similar decrease in the delay from symptom onset to patient arrival to the hospital. Given the publication of national guidelines on time to thrombolytic treatment and rigorous public education initiatives since 1990, the Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO-III) trial, completed in February 1997, afforded us a unique opportunity to examine this hypothesis. The parallel designs of these 2 studies also allowed us to study 2 large and very similar patient groups separated by several years in which awareness and treatment of myocardial infarction were rapidly evolving. We sought to isolate the factors associated with both out-of-hospital and inhospital delays. Furthermore, through socioeconomic information obtained in the GUSTO-III trial, we examined the impact of educational level, occupation, health care insurance status, and living alone on time delays. MATERIALS AND METHODS Our analysis population consisted of the patients enrolled in the United States in the GUSTO-I and GUSTO-III trials. This study was approved by the institutional review boards of all participating clinical sites. GUSTO-I enrolled 41,021 patients in a multicenter, international trial evaluating 4 fibrinolytic regimens of streptokinase and tissue plasminogen activator. Complete methods for the GUSTO-I trial have been published. 6 In this trial, patients were randomized to 1 of 4 fibrinolytic regimens if they presented within 6 hours after symptom onset and had chest pain lasting 20 minutes or more. In addition, patients must have had no contraindications to thrombolysis and must have met electrocardiographic criteria for infarction (ST-segment elevation 0.1 mv in 2 limb leads or 0.2 mv in at least 2 contiguous precordial leads). The GUSTO-III trial enrolled 15,060 patients; complete methods have been published. 7 Inclusion criteria for patients in GUSTO-III were identical to GUSTO-I. This randomized, controlled clinical trial compared 2 different fibrinolytic regimens: alteplase versus reteplase. Electrocardiographic criteria for determining infarction were similar to those in GUSTO-I. Because practice patterns vary substantially between countries, our evaluation was limited to the 23,105 GUSTO-I patients and 4,744 GUSTO-III patients enrolled in the United States. In GUSTO-I and GUSTO-III, 3 time variables were defined prospectively: (1) time from symptom onset to hospital arrival (out-of-hospital delay), (2) time from hospital arrival to administration of thrombolytic therapy (inhospital delay), and (3) total time from symptom onset to treatment. The temporal frames of 0 to 2 hours, 2 to 4 hours, and more than 4 hours were based on a prespecified analysis in GUSTO-I for time to hospital arrival from symptom onset and total time to treatment. For GUSTO- III, time from arrival to treatment was prospectively divided into 2 groups reflecting early treatment (<1 hour) and late treatment (>1 hour). For these analyses, the time of symptom onset was provided by the patient, or a family member if the patient was unable to communicate. The time of patient arrival to 124 ANNALS OF EMERGENCY MEDICINE 39:2 FEBRUARY 2002

hospital was derived from hospital records, as was time of administration of fibrinolytic therapy. For the GUSTO-I and GUSTO-III trials, information on baseline characteristics including age, sex, race, height, and weight were prospectively collected. We prospectively defined the following baseline characteristics for our analysis of their association with time to hospital arrival: history of hypertension, diabetes, smoking, hypercholesterolemia, family history, history of angina, myocardial infarction, coronary artery bypass grafting, and angioplasty. Physical examination data, including pulse rate, systolic and diastolic blood pressure, presence of congestive heart failure, and anatomic location of the infarction were also gathered. In GUSTO-III only, socioeconomic data were prospectively obtained to identify the impact of education level, occupation, payer status, and living alone on time to hospital arrival and time to treatment. Descriptive statistics, including percentages for discrete variables and medians with 25th and 75th percentiles for continuous variables, were used for baseline characteristic determination and time to treatment data for GUSTO-I and GUSTO-III patients. Statistical testing was performed using the χ 2 test for categoric variables and Cox modeling for continuous variables. A P value less than.05 was considered significant. Because enrollment criteria and baseline data in GUSTO-I and GUSTO-III were identical, these databases were combined to maximize power for the analysis. No distributional assumptions were made for the dependent variables, time to hospital arrival, and time from hospital arrival to treatment. On the basis of the GUSTO-I analysis that identified the principal features associated with delay in presentation, we performed a univariate analysis that identified age, sex, race, and diabetes as independent predictors of delay in hospital arrival for patients. Similarly, the patient s age, sex, race, pulse rate, previous angina, previous infarction, previous bypass surgery, and infarct location were found to be predictive of delay in time to treatment after hospital arrival. We then used stepwise regression modeling to evaluate the influence of socioeconomic factors on delay obtained in GUSTO-III. The socioeconomic factors that were evaluated included years of education, occupation, type of insurance, and living alone. RESULTS The baseline characteristics of patients enrolled in GUSTO-III were similar to those of patients enrolled in GUSTO-I. Thirty-day mortality was also similar for the 2 groups (Table 1). The time from symptom onset to hospital arrival did not change during the 7-year period from the start of GUSTO-I in 1990 to the end of GUSTO-III in 1997 (Table 2). The time from arrival to treatment with fibrinolytic Table 1. GUSTO-I and GUSTO-III baseline characteristics and mortality. GUSTO-I GUSTO-III Characteristic (n=23,105) (n=4,744) Age, y 61.1 (51.5, 69.8) 61.5 (51.5, 71.2) Female sex 6,278 (27.2) 1,346 (29.7) Weight, kg 80.2 (70.1, 91) 81.8 (71, 93) Height, cm 172.7 (165.1, 180) 172 (165, 179) Race Black 1,113 (4.8) 222 (4.9) Other 962 (4.2) 199 (4.4) White 20,962 (91.0) 4,108 (90.7) Hypertension 9,821 (42.7) 1,994 (44.0) Diabetes mellitus 3,820 (16.6) 819 (18.1) Hypercholesterolemia 8,473 (37.9) 1,873 (41.5) Previous myocardial infarction 3,943 (17.1) 809 (17.9) Systolic blood pressure, mm Hg 126 (110, 142) 133 (116, 150) Pulse rate, beats/min 74 (63, 86) 74 (62, 87) Killip class I 19,950 (87.1) 4,092 (91.4) II 2,507 (11.0) 334 (7.5) III 250 (1.1) 32 (0.71) IV 187 (0.82) 21 (0.47) Anterior infarction 8,591 (37.4) 1,994 (44.0) Inferior infarction 13,694 (59.6) 2,385 (52.6) Inhospital mortality 1,495 (6.5) 246 (5.4) Mortality by 30 d 1,562 (6.8) 286 (6.3) Results are expressed as numbers (percentages) or median (25th, 75th percentiles). Table 2. Comparison of the GUSTO-I trial to the GUSTO-III trial: Time from symptom onset to hospital arrival, hospital arrival to treatment, and time from symptom onset to treatment. GUSTO-I GUSTO-III P Interval Times (n=23,105) (n=4,744) Value Enrollment years 1990 1993 1995 1997 Symptom onset to hospital arrival, h 1.4 (0.9, 2.3) 1.4 (0.8, 2.3).09 Hospital arrival to treatment, h 1.1 (0.8, 1.5) 0.8 (0.6, 1.2) <.0001 Total time to treatment, h 2.7 (1.9, 3.8) 2.3 (1.6, 3.3) <.0001 Data are median (25th, 75th percentiles). FEBRUARY 2002 39:2 ANNALS OF EMERGENCY MEDICINE 125

therapy did decrease during this period, resulting in a decrease in total time from symptom onset to administration of therapy. Figure 1 provides a cumulative distribution plot of time from symptom onset to hospital arrival for GUSTO-I and GUSTO-III separately and with the 2 studies combined. Figure 2 shows the cumulative distribution plot of times from hospital presentation to treatment, reflecting the earlier treatment time for patients in GUSTO-III compared with GUSTO-I. The time from symptom onset to treatment is shorter for patients treated in GUSTO-III compared with GUSTO-I, reflecting reduced inhospital time to treatment; however, the symptom onset to hospital arrival curves are nearly identical for the 2 trials, suggesting no change in patient behavior during the 7-year period in which the 2 trials were conducted (Figure 3). The GUSTO-III data revealed a patient profile similar to GUSTO-I. Increased age, female sex, non-white race, hypertension, and diabetes were all associated with a longer time from onset of symptoms to treatment. Conversely, patients who smoked or had an elevated cholesterol level experienced a shorter total time from onset of symptoms to fibrinolytic therapy. Thirty-day mortality rates in GUSTO-III are comparable with those in GUSTO- I, suggesting that increased time to treatment, for any reason, resulted in increased mortality (Table 3). In GUSTO-III, patient characteristics associated with greater delay in the time from symptom onset to hospital arrival were similar to those in GUSTO-I (Table 3). In GUSTO-III, increased age (64 years versus 60 years; P=.001), female sex (35% versus 27%; P=.001), black race (6% versus 4%; P=.02), and diabetes (25% versus 16%; P=.001) were associated with delay in hospital presentation. Current smokers (46% versus 37%; P=.005) and patients with known coronary artery disease (previous angina [19% versus 14%; P=.006], infarction [19% versus 14%; P=.001], or angioplasty [11% versus 6%; P=.001]) tended to arrive at the hospital earlier. The finding that patients with preexisting angina arrived earlier to hospital in GUSTO-III did not parallel the GUSTO-I results, in which patients with previous angina tended to come to the hospital later. Patients with previous infarction or angioplasty, however, arrived earlier in both GUSTO-I and GUSTO-III. Inhospital and 30-day mortality rates demonstrated that a delay in arrival to the hospital is associated with increased mortality risk (8% versus 5% inhospital, P=.0001; 9% versus 5% 30-day, P=.001). Figure 1. Cumulative distribution plots of time from symptom onset to hospital arrival for the GUSTO-I and GUSTO-III trials. Cumulative distribution (%) 100 Figure 2. Cumulative distribution plots of time from hospital arrival to treatment for the GUSTO-I and GUSTO-III trials. Cumulative distribution (%) 100 80 75 60 50 40 25 GUSTO-I symptom onset to hospital arrival GUSTO-III symptom onset to hospital arrival 20 GUSTO-I hospital arrival to treatment GUSTO-III hospital arrival to treatment 0 0.00 1.00 2.00 3.00 4.00 5.00 Time (h) 0 0.00 1.00 2.00 Time (h) 126 ANNALS OF EMERGENCY MEDICINE 39:2 FEBRUARY 2002

When socioeconomic variables were added to this model, black race was no longer retained in the model and was not a significantly indicated risk for out-of-hospital delay. Educational status, however, was now a risk factor for delay in presentation. Patients who had completed college were significantly more likely (30% versus 26%; P=.002) to come to the hospital earlier (median difference 9 minutes) than patients who did not complete high school or who completed high school but not college. Whereas time to treatment inhospital decreased from 1990 to 1997, significant delays in therapy were evident for many patient groups. In GUSTO-III, increased age (64 years versus 60 years; P=.0001), female sex (34% versus 27%; P=.001), black race (7% versus 4%; P=.001), hypertension (48% versus 42%; P=.001), diabetes (21% versus 16%; P=.001), previous angina (46% versus 36%; P=.001), and previous infarction (21% versus 16%; P=.001) were associated with delays in treatment (Table 4). Patients with increased cholesterol levels (43% versus 39%; P=.006) and current smokers (47% versus 38%; P=.001) were treated earlier. Delay in treatment more than 1 hour after hospital arrival was associated with higher mortality rates inhospital (8% versus 4%; P=.001) and at 30 days (9% versus 5%; P=.001). A stepwise regression model combining the US cohorts of GUSTO-I and GUSTO-III identified age, systolic blood pressure, pulse rate, previous infarction, previous bypass surgery, previous angina, sex, race, and infarct location as predictive of time to treatment after hospital arrival. Men were treated 7 minutes faster than women. Patients with previous angina, previous infarction, and previous bypass surgery had delayed therapy (median differences were Table 3. The GUSTO-III trial: Characteristics associated with delay from symptom onset to hospital arrival with associated inhospital, 30- day mortality (early, 0 to 2 hours; late, >4 hours). 0 to 2 Hours 2 to 4 Hours >4 Hours P Characteristic (n=3,087) (n=1,146) (n=324) Value Age, y 60 (50, 70) 64 (53, 73) 64 (55, 74).001 Men 73 66 65.001 Race White 92 89 90.02 Black 4 7 6.02 Diabetes 16 20 25.001 Current smoker 46 42 37.005 Previous angina 19 16 14.006 Previous infarction 19 16 14.001 Previous angioplasty 11 8 6.001 Inhospital mortality 5 7 8.0001 Mortality (30 d) 5 9 9.001 Data are median (25th, 75th percentiles) or percentage of patients. P values for comparison of early versus late presenters to hospital. Figure 3. Cumulative distribution plots of time from symptom onset to treatment for the GUSTO-I and GUSTO-III trials. 100 80 60 40 20 Cumulative distribution (%) GUSTO-I symptom onset to treatment GUSTO-III symptom onset to treatment 0 0.00 1.00 2.00 3.00 4.00 5.00 6.00 7.00 Time (h) Table 4. The GUSTO-III trial: Characteristics associated with delays in treatment after hospital arrival with associated inhospital, 30- day mortality. 0 to 1 Hour >1 Hour P Characteristic (n=3,034) (n=1,514) Value Age, y 60 (51, 70) 64 (53, 73).0001 Men 73 66.001 Race White 92 88.001 Black 4 7.001 Hypertension 42 48.001 Diabetes 16 21.001 Hypercholesterolemia 43 39.006 Current smoker 47 38.001 Previous angina 36 46.001 Previous infarction 16 21.001 Inhospital mortality 4 8.001 Mortality (30 d) 5 9.001 Data are median (25th, 75th percentiles) or percentage of patients. P values for comparison of patients treated in the first hour after hospital arrival versus later. FEBRUARY 2002 39:2 ANNALS OF EMERGENCY MEDICINE 127

5.5, 4.8, and 6.0 minutes, respectively). Older patients were treated later, as were black patients (median delay of 12 minutes). Patients with inferior and anterior infarcts were treated 15 minutes earlier than patients with other infarct sites. Using GUSTO-III s socioeconomic data, we developed a new model containing the predictive factors of pulse rate, sex, previous angina, black race, infarct location, and whether the patient received public insurance. Patients with public insurance were treated, on average, 6 minutes later than those with private insurance. Patients with higher educational levels had decreased time from symptom onset to hospital arrival (30% versus 26%; P=.001; Table 5), as did individuals with management or professional occupations (28% versus 21%; P=.001). Having private insurance was associated with an earlier response to symptoms of AMI (64% versus 56%; P=.003), whereas patients with public insurance arrived later (36% versus 44%; P=.001). Living alone also resulted in a later arrival to the hospital compared with patients living with family or friends (18% versus 23%; P=.006). Patients with at least a high school education were treated sooner once in the emergency setting than those without this degree (Table 6). Homemakers or housewives received delayed treatment (9% versus 12%; P=.004), whereas individuals with a management or professional background experienced more rapid treatment (24% versus 23%; P=.026). Private insurance was associated with more rapid delivery of therapy inhospital (65% versus 58%; P=.001), whereas patients with public insurance tended to have delays in therapy (36% versus 45%; P=.001). Individuals without insurance were treated earlier as well (8% versus 6%; P=.013). DISCUSSION Early treatment of patients with AMI is critical to maximizing benefit. 8-10 Our study sought to identify factors associated with delays to hospital arrival as well as inhospital administration of thrombolytic therapy. In the GUSTO-I and GUSTO-III trials, the median time of delay from symptom onset to hospital arrival was 1.4 hours. During the 7 years between these 2 studies, despite widespread knowledge of the benefits of thrombolytic therapy among health care providers and extensive public education programs about AMI, early arrival to the hospital and treatment once in the hospital have not been realized. In particular, the same groups identified in a previous study Table 5. Socioeconomic factors associated with patient delays from symptom onset to hospital arrival. 0 to 2 Hours 2 to 4 Hours >4 Hours P Socioeconomic Factor (n=3,087) (n=1,146) (n=324) Value High school completed 74 68 70.001 College/university completed 30 24 26.002 Years of school completed 12 (12, 14) 12 (11, 13) 12 (11, 14) NS Current/principal past occupation Clerical/sales 19 21 20 NS Craftsman 9 9 9 NS Homemaker/housewife 10 11 12 NS Laborer 35 38 38 NS Management/professional 28 21 21.001 Type of insurance Private 64 60 56.003 Public 36 44 44.001 Other 2 2 3 NS None 7 6 8 NS Lives alone 18 21 23.006 NS, Not significant. Data are median (25th, 75th percentiles) or percentage of patients. P values for comparison of early versus late presenters to hospital. Table 6. Socioeconomic factors associated with delays in treatment after hospital arrival. 0 to 1 Hour >1 Hour P Socioeconomic Factor (n=3,034) (n=1,514) Value High school completed 73 69.017 College/university completed 29 27 NS Years of school completed 12 (12, 14) 12 (11, 14) NS Current/principal past occupation Clerical/sales 19 21 NS Craftsman 9 8 NS Homemaker/housewife 9 12.004 Laborer 36 36 NS Management/professional 24 23.026 Type of insurance Private 65 58.001 Public 36 45.001 Other 2 2 NS None 8 6.013 Lives alone 19 21 NS NS, Not significant. Data are median (25th, 75th percentiles) or percentage of patients. P values for comparison of patients treated in the first hour after hospital arrival versus later. 128 ANNALS OF EMERGENCY MEDICINE 39:2 FEBRUARY 2002

of GUSTO-I (conducted from 1990 through 1993) as susceptible to delay (elderly, women, patients with diabetes, and minorities) continue to arrive late to the hospital. 5 Other studies have confirmed that these patients are at risk for delay. 11-17 Education of patients identified as having increased risk for development of atherosclerosis and subsequent myocardial infarction would appear prudent. 18 The National Heart, Lung, and Blood Institute, through the National Heart Attack Alert Program, has supported educational initiatives through a mass media project: Rapid Early Action for Coronary Treatment (REACT). 19 Targeting such patients individually, through their family physician or pharmacist, may be more effective than mass media projects, which may not provide focus for patients at high risk. It would appear that some benefit of education was obtained in the years between the 2 trials for patients with previous angina. Although patients with pre-existing angina experienced a delay in hospital presentation in GUSTO I, this was not observed in GUSTO III. Ten years ago, initial studies evaluating time to treatment once the patient arrived at the hospital identified a typical 90-minute delay before infusion of fibrinolytic therapy. 20,21 Although substantial progress has been realized since then, national registries still identify delays of nearly 40 minutes. 4 In GUSTO-I, initiated in 1990, the median time from hospital arrival to treatment was 66 minutes. This period had decreased to 48 minutes when measured in GUSTO-III, which was completed 7 years later. Patients with previous angina, infarction, and angioplasty tended to present to the hospital earlier with AMI. Paradoxically, these patients with known coronary artery disease tended to have delays in delivery of fibrinolytic therapy. There are multiple possible reasons for this inhospital delay in therapy. Patients presenting with preexisting coronary artery disease often have baseline electrocardiographic abnormalities that can confound the diagnosis of an acute injury. Typically, the old ECG or the patient s medical records, which describe a previous procedure or hospitalization, must then be obtained from another area of the institution or from another hospital system entirely; this can serve as a significant source of delay in diagnosis. In a similar fashion, contacting the patient s primary care physician or cardiologist for consultation while the patient is in the ED is often necessary for these patients and can also retard treatment. One finding of this study was that certain groups of patients are especially prone to experience inhospital treatment delays. Among these are patient subgroups at risk for out-of-hospital delay as well, including the elderly, women, minorities, and patients with diabetes. 5,13,22 Although multiple studies have identified female patients as prone to delays in therapy, 13,18 the other groups have received less attention. Elderly patients with diabetes are known to have atypical symptoms associated with AMI. 23,24 These less typical symptoms serve to confound the clinician in the emergency setting caring for these patients, thus increasing the likelihood of a delay in diagnosis and treatment once the patient arrives at the hospital. Further education of health care providers is essential to prospectively identify these high-risk groups and subsequently to pursue approaches to decrease time to treatment for these patients. The GUSTO-III study prospectively identified the influence of socioeconomic factors on time to hospital arrival and time to treatment. A patient s educational level, occupation, health insurance, and the presence of family or friends in the home appear to affect health careseeking behavior. Health care provider behavior appears to be influenced as well. A higher educational level and occupations defined as management or professional are associated with earlier times to hospital arrival and treatment. The more highly educated patient may be aware of the symptoms and risk factors associated with AMI, prompting earlier hospital arrival. Once in hospital, the patient with a higher educational level may better articulate this symptom complex, allowing the treating physician to make a more rapid decision. Similarly, in patients with symptoms of myocardial infarction, having private health insurance is linked with earlier arrival to the hospital and more rapid administration of fibrinolytic therapy compared with public insurance. 25-27 Living alone also led to a delay in arrival, perhaps as a result of the lack of family or friends necessary to convince a patient of the severity or importance of their symptoms. Other factors, such as education level, availability of a telephone, or income level could also influence the behavior of the patient living alone. This study evaluating nearly 28,000 patients with myocardial infarction treated in the United States during the GUSTO-I and GUSTO-III trials identifies a number of patients at risk for not receiving thrombolytic therapy early in the course of their infarction. Significant delays in hospital arrival and treatment still exist nearly a decade after the original GUSTO-I trial, suggesting that further effort is necessary to educate patients and health care providers. Although special educational efforts should be targeted to those individuals known to be at high risk for delays in hospital arrival and treatment, such as women, FEBRUARY 2002 39:2 ANNALS OF EMERGENCY MEDICINE 129

the elderly, and those with less formal education, patients who are not members of these particular groups also suffer delays and require education about AMI. 28 The timedependent nature of thrombolytic treatment for myocardial infarction represents a critical public health education challenge. Biostatistical information is included in the full-text, online version of this article. Access the Annals Web site at www.mosby.com/annemergmed. Information is also available at ACEP s home page at www.acep.org/annemergmed. Author contributions: WBG, PWA, EMO, and WDW conceived the study, designed the analysis, and supervised the conduct of the study. ALS and RMC managed the data and provided data analyses. JMG and LKN helped to recruit centers, enroll patients, and manage data. RMC and EJT obtained research funding for the trial, conceived of the primary trial, and recruited sites. WBG drafted the manuscript and all authors contributed substantially to its revision. 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