Comparative Effectiveness of Aspirin Dosing in Cardiovascular Disease and Diabetes Mellitus: A Subgroup Analysis of the ADAPTABLE Trial.

OBJECTIVE: Patients with diabetes mellitus (DM) and concomitant atherosclerotic cardiovascular disease (ASCVD) must be on the most effective dose of aspirin to mitigate risk of future adverse cardiovascular events. RESEARCH DESIGN AND METHODS: ADAPTABLE, an open-label, pragmatic study, randomized patients with stable, chronic ASCVD to 81 mg or 325 mg of daily aspirin. The effects of aspirin dosing was assessed on the primary effectiveness outcome, a composite of all-cause death, hospitalization for myocardial infarction, or hospitalization for stroke, and the primary safety outcome of hospitalization for major bleeding. In this prespecified analysis, we used Cox proportional hazards models to compare aspirin dosing in patients with and without DM for the primary effectiveness and safety outcome. RESULTS: Of 15,076 patients, 5,676 (39%) had DM of whom 2,820 (49.7%) were assigned to 81 mg aspirin and 2,856 (50.3%) to 325 mg aspirin. Patients with versus without DM had higher rates of the composite cardiovascular outcome (9.6% vs. 5.9%; P < 0.001) and bleeding events (0.78% vs. 0.50%; P < 0.001). When comparing 81 mg vs. 325 mg of aspirin, patients with DM had no difference in the primary effectiveness outcome (9.3% vs. 10.0%; hazard ratio [HR] 0.98 [95% CI 0.83-1.16]; P = 0.265) or safety outcome (0.87% vs. 0.69%; subdistribution HR 1.25 [95% CI 0.72-2.16]; P = 0.772). CONCLUSIONS: This study confirms the inherently higher risk of patients with DM irrespective of aspirin dosing. Our findings suggest that a higher dose of aspirin yields no added clinical benefit, even in a more vulnerable population.

Prevalent digoxin use and subsequent risk of death or hospitalization in ambulatory heart failure patients with a reduced ejection fraction-Findings from the Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training (HF-ACTION) randomized controlled trial.

BACKGROUND: Despite more than 200 years of clinical experience and a pivotal trial, recently published research has called into question the safety and efficacy of digoxin therapy in heart failure (HF). METHODS: HF-ACTION (ClinicalTrials.gov Number: NCT00047437) enrolled 2331 outpatients with HF and an EF ≤35% between April 2003 and February 2007 and randomized them to aerobic exercise training versus usual care. Patients were grouped according to prevalent digoxin status at baseline. The association between digoxin therapy and outcomes was assessed using Cox proportional hazard and inverse-probability weighted (IPW) regression models adjusted for demographics, medical history, medications, laboratory values, quality of life, and exercise parameters. RESULTS: The prevalence of digoxin therapy decreased from 52% during the first 6 months of enrollment to 35% at the end of the HF-ACTION trial (P <0.0001). Study participants were 59± 13 years of age, 72% were male, and approximately half had an ischemic etiology of HF. Patients receiving digoxin at baseline tended to be younger and were more likely to report New York Heart Association functional class III/IV symptoms (rather than class II) compared to those not receiving digoxin. Patients taking digoxin had worse baseline exercise capacity as measured by peak VO2 and 6-min walk test and greater impairments in health status as reflected by the Kansas City Cardiomyopathy Questionnaire. The association between digoxin and the risk of death or hospitalization differed depending on whether Cox proportional hazard (Hazard Ratio 1.03, 95% Confidence Interval 0.92-1.16; P = .62) or IPW regression models (HR 1.08, 95% CI 1.00-1.17; P = .057) were used to adjust for potential confounders. CONCLUSION: Although digoxin use was associated with high-risk clinical features, the association between digoxin therapy and outcomes was dependent on the statistical methods used for multivariable adjustment. Clinical equipoise exists and additional prospective research is required to clarify the role of digoxin in contemporary clinical practice including its effects on functional capacity, quality of life, and long-term outcomes.

Pooled analysis of adverse event collection from 4 acute coronary syndrome trials.

BACKGROUND: Adverse event collection in randomized clinical trials establishes drug safety. Although costly and regulated, it is rarely studied. METHODS: Adverse event data from 4 clinical trials (APPRAISE-2, PLATO, TRACER, TRILOGY ACS) comprising 48,118 participants with acute coronary syndromes were pooled to compare patterns and determinants of reporting. Events were classified as serious (SAE) or nonserious (AE) from hospital discharge to 1 year; study end points were excluded. RESULTS: In total, 84,901 events were reported. Of those, 12,266 (14.4%) were SAEs and 72,635 (85.6%) were AEs. Of all participants, 7,823 (16.3%) had SAEs, 18,124 (37.7%) had only AEs, and 22,171 (46.1%) had neither. Nonserious adverse events were distributed across system organ classes: general disorders (11%), infection (10%), gastrointestinal (10%), respiratory (9%), cardiovascular (8.4%), and other (35%). Serious adverse events had a higher proportion of cardiovascular causes (14.0%). Event reporting was highest after hospital discharge, decreasing rapidly during the following 3 months. In a Cox proportional hazards model, chronic obstructive pulmonary disease (hazard ratio 1.58, 95% CI 1.44-1.74), heart failure (1.55, 1.40-1.70), older age, and female sex were independent predictors of more SAEs, whereas enrollment in Eastern Europe (0.63, 0.58-0.69) or Asia (0.84, 0.75-0.94) were independent predictors of fewer SAEs. CONCLUSIONS: Half of all participants reported adverse events in the year after acute coronary syndrome; most were AEs and occurred within 3 months. The high volume of events, as well as the variation in SAE reporting by characteristics and enrollment region, indicates that efforts to refine event collection in large trials are warranted.

Age and outcomes in ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention: findings from the APEX-AMI trial.

BACKGROUND: To understand the influence of age on treatment and outcomes, we analyzed the largest group of patients 75 years or older with ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention (PPCI) in a clinical trial. METHODS: We analyzed data from 5745 patients in the Assessment of Pexelizumab in Acute Myocardial Infarction trial from July 13, 2004, through May 11, 2006. Age was analyzed continuously and according to 3 groups: younger than 65 years (n = 3410), 65 to 74 years old (n = 1358), and 75 years or older (n = 977). The main outcome measures were 90-day mortality and the composite of congestive heart failure, shock, or death at 90 days. RESULTS: Older patients had higher rates of hypertension, chronic obstructive lung disease, previous angina, and prior revascularization. Also notable in these patients were higher Killip class, less angiographic success after PPCI, and less ST-segment resolution with higher rates of in-hospital clinical events, including mechanical, electrical, and bleeding complications. There was less use of short-term adjunctive medications but similar use of discharge medications in older compared with younger patients. Ninety-day mortality rates were 2.3%, 4.8%, and 13.1%; composite outcome rates were 5.9%, 11.9%, and 22.8% for patients younger than 65 years, 65 to 74 years old, and 75 years or older, respectively. After multivariable adjustment, age was the strongest independent predictor of 90-day mortality (hazard ratio, 2.07 per 10-year increase; 95% confidence interval, 1.84-2.33). CONCLUSIONS: Older patients have lower rates of acute procedural success and more postinfarction complications. Age is the strongest predictor of 90-day mortality in ST-segment elevation myocardial infarction patients undergoing PPCI. Despite implementing PPCI for ST-segment elevation myocardial infarction in older patients, early risk remains high, necessitating continued focus on improving outcomes in this vulnerable population.

Mortality implications of primary percutaneous coronary intervention treatment delays: insights from the Assessment of Pexelizumab in Acute Myocardial Infarction trial.

BACKGROUND: Prior studies demonstrate a direct relationship between treatment delays to primary percutaneous intervention and mortality in patients with ST-segment elevation myocardial infarction (STEMI). This analysis compared the relationship of symptom onset-to-balloon time and door-to-balloon time on mortality in patients with STEMI. METHODS AND RESULTS: We analyzed different treatment delays (symptom onset-to-balloon time, door-to-balloon time) and mortality in 5745 STEMI patients. Baseline characteristics, flow grade, 90-day mortality, and clinical outcomes were compared in patients stratified by treatment delay. Multivariable logistic regression modeling was performed to assess the independent and relative effect of each treatment delay on 90-day mortality. Female sex, increased age, and worse thrombolysis in myocardial infarction flow grade were significantly associated with longer symptom onset-to-balloon times and door-to-balloon times. Longer symptom onset-to-balloon time was significantly associated with worse 90-day mortality (3.7%, 4.2%, and 6.5% for time delays <3 hours, 3 to 5 hours, and >5 hours, respectively, P<0.0001). Similarly, longer door-to-balloon times were significantly associated with worse 90-day mortality (3.2%, 4.0%, 4.6%, and 5.3% for delays <60 minutes, 60 to 90 minutes, 90 to 120 minutes, and ≥120 minutes respectively, P<0.0001). In a multivariate model of 90-day mortality, door-to-balloon time (χ(2) 6.0, P<0.014), and symptom onset-to-hospital arrival (χ(2) 9.8, P<0.007) remained independent determinants. CONCLUSIONS: Both symptom onset-to-balloon time and hospital door-to-balloon time are strongly associated with 90-day mortality following STEMI. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT00091637.

Association of mortality with years of education in patients with ST-segment elevation myocardial infarction treated with fibrinolysis.

OBJECTIVES: The purpose of this study was to examine the association between lower socioeconomic status (SES), as ascertained by years of education, and outcomes in patients with acute ST-segment elevation myocardial infarction (STEMI). BACKGROUND: Previous studies have shown an inverse relationship between SES and coronary heart disease and mortality. Whether a similar association between SES and mortality exists in STEMI patients is unknown. METHODS: We evaluated 11,326 patients with STEMI in the GUSTO-III (Global Use of Strategies to Open Occluded Coronary Arteries) trial study from countries that enrolled >500 patients. We evaluated clinical outcomes (adjusted using multivariate regression analysis) according to the number of years of education completed. RESULTS: One-year mortality was inversely related to years of education and was 5-fold higher in patients with <8 years compared with those with >16 years of education (17.5% vs. 3.5%, p < 0.0001). The strength of the relationship between education and mortality varied among different countries. Nonetheless, years of education remained an independent correlate of mortality at day 7 (hazard ratio per year of increase in education: 0.86; 95% confidence interval: 0.83 to 0.88) and also between day 8 and 1 year (hazard ratio per year of increase in education: 0.96; 95% confidence interval: 0.94 to 0.98), even after adjustment for baseline characteristics and country of enrollment. CONCLUSIONS: When the number of years of education was used as a measure of SES, there was an inverse relationship such that significantly higher short-term and 1-year mortality existed beyond that accounted for by baseline clinical variables and country of enrollment. Future studies should account for and investigate the mechanisms underlying this link between SES and cardiovascular disease outcomes.

Predictors of 30-day mortality in patients with refractory cardiogenic shock following acute myocardial infarction despite a patent infarct artery.

BACKGROUND: Little is known about predictors of survival in patients with persistent shock following acute myocardial infarction (MI) despite a patent infarct artery. METHODS: We examined data from TRIUMPH, a multicenter randomized clinical trial of the nitric oxide synthase inhibitor, L-N(G)-monomethyl-arginine, in patients with persistent vasopressor-dependent cardiogenic shock complicating acute MI at least 1 hour after established infarct-related artery patency. Patients who died within 30 days were compared with those who survived. Continuous variables were assessed using the Wilcoxon rank sum and categorical variables using the chi(2) test. Prespecified baseline variables were included in a multivariable logistic regression model to predict mortality. A second model incorporating baseline vasopressors and dosages and a third model including change in systolic blood pressure at 2 hours were also developed. Bootstrapping was used to assess the stability of model variables. RESULTS: Of 396 patients, 180 (45.5%) died within 30 days. Systolic blood pressure (SBP), measured on vasopressor support, and creatinine clearance were significant predictors of mortality in all models. The number of vasopressors and norepinephrine dose were also predictors of mortality in the second model, but the latter was no longer significant when change in SBP at 2 hours was added as a covariate in the third model. CONCLUSIONS: The SBP, creatinine clearance, and number of vasopressors are significant predictors of mortality in patients with persistent vasopressor-dependent cardiogenic shock following acute MI despite a patent infarct artery. These prognostic variables may be useful for risk-stratification and in selecting patients for investigation of additional therapies.

Preliminary experience with intravenous P2Y12 platelet receptor inhibition as an adjunct to reduced-dose alteplase during acute myocardial infarction: results of the Safety, Tolerability and Effect on Patency in Acute Myocardial Infarction (STEP-AMI) angiographic trial.

BACKGROUND: Fibrinolytic therapy for acute myocardial infarction (AMI) results in normal flow in only about half of patients. Adjunctive treatment with potent antiplatelet and antithrombin agents increases arterial patency but is associated with excessive bleeding. Cangrelor (formerly AR-C69931MX) is a rapidly acting, specific antagonist of platelet aggregation via binding to the adenosine diphosphate P2Y12 receptor subtype. The aim of this study was to assess the safety and coronary artery patency of cangrelor as an adjunct to alteplase (tissue plasminogen activator [t-PA]). METHODS: Patients with AMI received aspirin, heparin, and an intravenous infusion of either cangrelor alone, full-dose t-PA alone, or 1 of 3 doses of cangrelor along with half-dose t-PA. The primary end point was Thrombolysis in Myocardial Infarction (TIMI) grade 3 flow at 60 minutes. Secondary end points included TIMI frame count, TIMI myocardial perfusion grade, extent of ST-segment resolution, composite clinical events, and bleeding. RESULTS: Ninety-two of planned 180 patients were enrolled. The combination of cangrelor and half-dose t-PA resulted in similar 60-minute patency as full-dose t-PA alone (55% vs 50%, P = not significant) and greater patency than with cangrelor alone (55% vs 18%, P < .05). The percentage of patients achieving >70% ST-segment resolution at 60 minutes tended to be greater with combination therapy than with either cangrelor or t-PA alone (28% vs 13%, P = .13 and 28% vs 14%, P = .30, respectively). Bleeding and adverse clinical events were comparable among the groups. CONCLUSION: This first experience with the intravenous P2Y12 receptor inhibitor, cangrelor, suggests the potential of this compound as an adjunct to fibrinolysis during treatment of AMI.

Effect of nitric oxide synthase inhibition on haemodynamics and outcome of patients with persistent cardiogenic shock complicating acute myocardial infarction: a phase II dose-ranging study.

AIMS: Previous studies suggested haemodynamic benefits and, possibly, mortality reduction with the use of nitric oxide synthase (NOS) inhibition in patients with acute myocardial infarction (AMI) complicated by cardiogenic shock (CS). We assessed preliminary efficacy and safety of four doses of l-n-monomethyl-arginine (l-NMMA), a non-selective NOS inhibitor, in patients with AMI complicated by CS despite an open infarct-related artery. METHODS AND RESULTS: Patients (n = 79) were randomly assigned to a bolus and 5 h infusion of placebo or 0.15, 0.5, 1.0, or 1.5 mg/kg of l-NMMA. The primary outcome measure was absolute change in mean arterial pressure (MAP) at 2 h. Fifteen minutes after study drug initiation, mean change in MAP was -4.0 mmHg in the placebo group and 5.8 (P = 0.02), 4.8 (P = 0.02), 5.1 (P = 0.07), and 11.6 (P < 0.001) mmHg in the four l-NMMA groups, respectively (all vs. placebo). Mean change in MAP at 2 h was -0.4, 4.4, 1.8, -4.1, and 6.8 mmHg in the placebo and four l-NMMA groups, respectively (all P = NS). CONCLUSION: l-NMMA resulted in modest increases in MAP at 15 min compared with placebo but there were no differences at 2 h.

Effect of tilarginine acetate in patients with acute myocardial infarction and cardiogenic shock: the TRIUMPH randomized controlled trial.

CONTEXT: Cardiogenic shock complicating acute myocardial infarction (MI) remains a common and lethal disorder despite aggressive use of early revascularization. Systemic inflammation, including expression of inducible nitric oxide synthase (NOS) and generation of excess nitric oxide, is believed to contribute to the pathogenesis and inappropriate vasodilatation of persistent cardiogenic shock. Preliminary, single-center studies suggested a beneficial effect of NOS inhibition on hemodynamics, renal function, and survival in patients with cardiogenic shock. OBJECTIVE: To examine the effects of an isoform-nonselective NOS inhibitor in patients with MI and refractory cardiogenic shock despite establishment of an open infarct artery. DESIGN, SETTING, AND PATIENTS: International, multicenter, randomized, double-blind, placebo-controlled trial (Tilarginine Acetate Injection in a Randomized International Study in Unstable MI Patients With Cardiogenic Shock [TRIUMPH]) with planned enrollment of 658 patients at 130 centers. Participants were enrolled between January 2005 and August 2006 when the study was terminated early. INTERVENTION: Tilarginine (L-N(G)-monomethylarginine [L-NMMA]), 1-mg/kg bolus and 1-mg/kg per hour 5-hour infusion, vs matching placebo. MAIN OUTCOME MEASURES: The primary outcome was 30-day all-cause mortality among patients who received study medication. Secondary outcomes included shock resolution and duration, New York Heart Association (NYHA) functional class at 30 days, and 6-month mortality. RESULTS: Enrollment was terminated at 398 patients based on a prespecified futility analysis. Six-month follow-up was completed in February 2007. There was no difference in 30-day all-cause mortality between patients who received tilarginine (97/201 [48%]) vs placebo (76/180 [42%]) (risk ratio, 1.14; 95% confidence interval, 0.92-1.41; P = .24). Resolution of shock (133/201 [66%] tilarginine vs 110/180 [61%] placebo; P = .31) and duration of shock (median, 156 [interquartile range, 78-759] hours tilarginine vs 190 [100-759] placebo; P = .16) were similar. At 30 days a similar percentage of patients had heart failure (48% tilarginine vs 51% placebo; P = .51) with a similar percentage of those patients in NYHA class I/II (73% tilarginine vs 75% placebo; P = .27). After 6 months mortality rates were similar in the 2 groups (58% tilarginine vs 59% placebo; hazard ratio, 1.04; 95% confidence interval, 0.79-1.36; P = .80). CONCLUSIONS: Tilarginine, 1-mg/kg bolus and 5-hour infusion, did not reduce mortality rates in patients with refractory cardiogenic shock complicating MI despite an open infarct artery. Early mortality rates in this patient group are high. Further research is needed to develop effective therapies for patients with cardiogenic shock following acute MI. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00112281

Benefits of direct angioplasty for women and men with acute myocardial infarction: results of the Global Use of Strategies to Open Occluded Arteries in Acute Coronary Syndromes Angioplasty (GUSTO II-B) Angioplasty Substudy.

BACKGROUND: Direct angioplasty (PTCA) and thrombolytic therapy are the chief therapies for treating an ST-segment elevation myocardial infarction (MI). OBJECTIVE: This study was designed to evaluate sex differences in the relative benefit of direct PTCA versus thrombolytic therapy among patients enrolled in the Global Use of Strategies to Open Occluded Arteries in Acute Coronary Syndromes Angioplasty (GUSTO II-B PTCA) Substudy. METHODS: Women and men presenting with an acute ST-segment elevation MI were randomized to receive either direct PTCA or accelerated tissue plasminogen activator (t-PA). Patients were then randomized to treatment with either heparin or bivalirudin. A gender analysis of outcome was performed. RESULTS: Women were older than men (68.6 +/- 11.5 vs 59.5 +/- 12.0 years, P <.001) and were more likely to have diabetes (22.5% vs 13.5%, P <.0001) and hypertension (53.3% vs 34.8%, P =.001). After adjusting for differences in baseline variables, the odds ratio (OR) for reaching a 30-day clinical end point (death, nonfatal infarction, or nonfatal disabling stroke) was similar for women and men (1.35, 95% CI 0.88-2.08). The OR for reaching a clinical end point at 30 days for the PTCA-treated women compared with the t-PA-treated women was 0.685 (95% CI 0.36-1.32) and similar to the OR in men, 0.565 (95% CI 0.35-0.91), P for interaction =.535. Because women had a higher event rate than men, the absolute number of major events prevented when treating women with direct PTCA was higher than men (56 events/1000 women treated with PTCA vs 42 events per 1000 men treated with PTCA). CONCLUSIONS: Although the relative benefit of direct PTCA to t-PA for the treatment of an acute MI appears to be similar in women and men, women may derive a larger absolute benefit from direct PTCA.

Sustained ventricular arrhythmias and mortality among patients with acute myocardial infarction: results from the GUSTO-III trial.

BACKGROUND: In many patients, ventricular arrhythmias will develop early after acute myocardial infarction. We studied the incidence, timing, and outcomes of such arrhythmias in the international Global Utilization of Streptokinase and TPA (alteplase) for Occluded Coronary Arteries (GUSTO)-III trial. METHODS: We identified independent predictors of inhospital ventricular fibrillation (VF) and ventricular tachycardia (VT) and compared 30-day and 1-year mortality rates of patients who did (n = 1121) and did not (n = 13,921) have these arrhythmias during the index hospitalization. RESULTS: Significant independent predictors of inhospital VF were higher Killip class, lower baseline systolic pressure, intravenous preenrollment lidocaine use, shorter time to thrombolysis, and beta-blocker use <2 weeks before enrollment; independent predictors of inhospital VT were lower baseline systolic pressure, intravenous lidocaine use before enrollment, higher Killip class, faster baseline heart rate, and advanced age. The 30-day mortality rate was 31% in patients with VF, 24% in those with VT, 44% in those with both, and 6% in those with neither (P =.001). The corresponding 1-year mortality rates were 34%, 29%, 49%, and 9% (P =.001). The 30-day and 1-year mortality rates were higher for patients with late (>48 hours after enrollment) versus early arrhythmias (< or =48 hours after enrollment). CONCLUSIONS: Despite thrombolysis, inhospital ventricular arrhythmias are associated with higher 30-day and 1-year mortality rates after acute myocardial infarction, particularly when occurring later during the initial hospitalization. Better therapies are needed to improve outcomes of these arrhythmias.

Predicting outcome after thrombolysis in acute myocardial infarction according to ST-segment resolution at 90 minutes: a substudy of the GUSTO-III trial. Global Use of Strategies To Open occluded coronary arteries.

BACKGROUND: Resolution of ST-segment elevation after thrombolysis for acute myocardial infarction has been shown to have prognostic significance 3 hours (180 minutes) after the initiation of therapy. Whether prognostically useful information can be achieved as early as 90 minutes after thrombolysis is unknown. METHODS: An electrocardiographic substudy of 2352 patients from the Global Use of Strategies To Open occluded coronary arteries (GUSTO-III) trial was undertaken to compare outcomes according to ST-segment resolution at 90 minutes versus 180 minutes after administration of thrombolytic therapy. RESULTS: Of 2352 patients in the substudy, 2241 had a baseline and 90-minute electrocardiogram, and 2218 had a baseline and 180-minute ECG. Complete ST-segment resolution occurred in 44.2% of patients at 90 minutes and 56.5% of patients at 180 minutes. ST-segment resolution at both 90 and 180 minutes was associated with lower 30-day and 1-year mortality. Multivariate analysis revealed ST-segment resolution at 90 minutes to be an equally strong predictor of 30-day mortality as resolution at 180 minutes. Patients who were at particularly high risk for mortality were those aged >70 years, those who presented with Killip class >1, and those with anterior infarctions. CONCLUSIONS: The presence of ST-segment resolution on standard 12-lead electrocardiographic monitoring 90 minutes after thrombolysis is a useful independent predictor of mortality at 30 days and 1 year. The potential for obtaining prognostic results as early as 90 minutes after thrombolysis sets a new precedent for optimum electrocardiographic monitoring times in these patients.

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

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 in hospital 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 in hospital, 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 in hospital 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.