Original Contributions
Persistence of delays in presentation and treatment for patients with acute myocardial infarction: The GUSTO-I and GUSTO-III experience*,**

https://doi.org/10.1067/mem.2002.121402Get rights and content

Abstract

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 setting. 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.

Section snippets

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

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).

. GUSTO-I and GUSTO-III baseline characteristics and mortality.*

CharacteristicGUSTO-I (n=23,105)GUSTO-III (n=4,744)
Age, y61.1 (51.5, 69.8)61.5 (51.5, 71.2)
Female sex6,278 (27.2)1,346 (29.7)
Weight, kg80.2 (70.1, 91)81.8 (71, 93)
Height, cm172.7 (165.1, 180)172 (165, 179)
Race
Black1,113 (4.8)222 (4.9)
Other962 (4.2)199

Discussion

Early treatment of patients with AMI is critical to maximizing benefit.8, 9, 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

Acknowledgements

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

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    *

    Author contributions are provided at the end of this article.

    **

    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 [email protected].

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