METHODS: The Canadian ACS2, Global Registry of Acute Coronary Events (GRACE/GRACE(2)), and Canadian Registry of Acute Coronary Events (CANRACE) were used to obtain data on 10,667 non-ST segment elevation acute coronary syndrome (NSTEACS) patients between 2002 and 2008. Multivariable analysis was used to examine the relationships between the number of vascular beds affected and both in-hospital coronary angiography and in-hospital mortality. The ACS2 registry (2002-2003) included physician-reported reasons for non-invasive management, which were stratified by vascular disease burden.

RESULTS: Patients with more vascular disease had higher GRACE risk scores at presentation, but less frequently received antiplatelet agents and angiography. The most common reason in the ACS2 registry for patients who did not undergo angiography was "not high enough risk." There was an independent inverse relationship between the extent of vascular disease and in-hospital angiography. Patients with higher vascular disease burden had higher unadjusted in-hospital mortality. In multivariable analysis, patients with 1 vascular territory affected had the lowest and those with 3 vascular beds affected had the highest adjusted in-hospital mortality. In the ACS2 registry, patients with more extensive vascular disease had higher rates of 1-year mortality and death/re-infarction (both p for trend <0.001).

CONCLUSIONS: NSTEACS patients with more vascular disease received less intensive treatment, with an associated worse outcome. This undertreatment might be partly mediated by physicians' underestimation of patient risk. More aggressive risk factor modification and intensive ACS therapies may improve the outcome of these high-risk patients.

Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Aims: To describe the characteristics, treatment, and mortality in patients with ST-elevation myocardial infarction (STEMI) by use of chronic oral anticoagulant (OAC) therapy.

Methods: Using data from the Global Registry of Acute Coronary Syndromes (GRACE), patient characteristics, treatment, and reperfusion strategies of STEMI patients on chronic OAC are described, and relevant variables compared with patients not on chronic OAC. Six-month post-discharge mortality rates were evaluated by Cox proportional hazard models.

Results: Of 19,094 patients with STEMI, 574 (3.0%) were on chronic OAC at admission. Compared with OAC non-users, OAC users were older (mean age 73 vs. 65 years), more likely to be female (37 vs. 29%), were more likely to have a history of atrial fibrillation, prosthetic heart valve, venous thromboembolism, or stroke/transient ischaemic attack, had a higher mean GRACE risk score (166 vs. 145), were less likely to be Killip class I (68 vs. 82%), and were less likely to undergo catheterization/percutaneous coronary intervention (52 vs. 66%, respectively). Of the patients who underwent catheterization, fewer OAC users had the procedure done within 24 h of admission (56.5 vs. 64.5% of OAC non-users). In propensity-matched analyses (n=606), rates of in-hospital major bleeding and in-hospital and 6-month post-discharge mortality were similar for OAC users and OAC non-users (2.7 and 3.7%, p=0.64; 15 and 13%, p=0.56; 15 and 12%, p=0.47, respectively), rates of in-hospital recurrent myocardial infarction (8.6 and 2.0%, pp=0.004) were higher in OAC patients, and rates of 6-month stroke were lower (0.6 and 4.3%, p=0.038). Patients in both groups who underwent catheterization had lower mortality than those who did not undergo catheterization.

Conclusions: This is the largest study to describe the characteristics and treatment of STEMI patients on chronic OAC. The findings suggest that patients on chronic OAC are less likely to receive guideline-indicated management, but have similar adjusted rates of in-hospital and 6-month mortality.

Methods and results: A total of 2099 ACS patients enrolled in the Global Registry of Acute Coronary Events (GRACE) UK-Belgian study were prospectively followed for a median of 5 years (1668 days). C-allele carriers of the rs579459 variant, which is located upstream of the ABO gene and correlates with blood group A, were independently associated with recurrent MI [multivariable-adjusted hazard ratio (HR) 2.25, CI = 1.37-3.71; P = 0.001] and with recurrent MI or cardiac death [multivariable-adjusted (HR) 1.80, CI = 1.09-2.95; P = 0.021] within 5 years after an index ACS. The association of rs579459 was replicated in 1250 Polish patients with 6 months follow-up after an index ACS [multivariable-adjusted (HR) 2.70, CI = 1.26-5.82; P = 0.011 for recurrent MI]. Addition of rs579459 to a prediction model of 17 clinical risk factors improved risk classification for recurrent MI or cardiac death at 6 months as calculated by the integrated discrimination improvement method (P = 0.037), but not by C-statistics (P = 0.096).

Conclusion: In this observational study, rs579459 was independently associated with adverse cardiac outcome after ACS. A weak improvement in clinical risk prediction was also observed, suggesting that rs579459 should be further tested as a potentially relevant contributor to risk prediction models for adverse outcome following ACS.

Objective Non-alcoholic fatty liver disease (NAFLD) is associated with a higher risk of cardiovascular disease, but no data exist about the relation between NAFLD and adverse outcomes in persons with acute coronary syndromes (ACS). We evaluated elevated serum alanine aminotransferase (ALT) as a marker of NAFLD, in association adverse outcomes following ACS.

Methods We conducted a retrospective cohort study of participants enrolled in the Global Registry of Acute Coronary Events (GRACE) admitted for ACS to St Michael's Hospital, Toronto, between 1999 and 2007. Multivariable linear regression was used to determine the change in maximum measured cardiac troponin I (cTnI) per each 1 IU/l increase in serum ALT concentration. The association between an elevated ALT >90th centile, and adverse outcomes in-hospital and at 6 months were calculated using multiple logistic regression analyses, adjusting for age, sex, body mass index, serum creatinine, glucose, triglycerides and LDL-C, as well as chronic statin or other lipid-lowering agent use.

Results 528 participants were included. Each 1 IU/l increase in ALT was associated with an increase in maximum measured cTnI of 0.16 µg/l (95% CI 0.10 to 0.22). An elevated ALT concentration >90th percentile was associated with a maximum measured cTnI in the highest quartile (adjusted OR 7.07, 95% CI 1.83 to 27.37). An elevated ALT >90th percentile was also significantly associated with all-cause mortality in-hospital, and up to 6 months after discharge (adjusted OR 8.96, 95% CI 3.28 to 24.49).

Conclusions NAFLD, determined by an elevated serum ALT, is associated with a higher risk of adverse outcomes in persons with ACS. Whether ALT is a valid and independent prognostic marker in ACS remains to be determined.

METHODS: The objectives of this large multinational observational study were to describe recent trends in these and related endpoints among adult men and women younger than 55 years of age who were hospitalized with an ACS between 1999 and 2007 as part of the Global Registry of Acute Coronary Events (GRACE) study.

RESULTS: The overall proportion of young adults hospitalized with an ACS in our multinational study population was 23% (n=15 052 of 65 119); this proportion remained relatively constant during the years under study. The proportion of comparatively young patients hospitalized with a previous diagnosis of angina pectoris or heart failure decreased over time, whereas the rates of previously diagnosed hypertension in this patient population increased. The proportion of patients developing atrial fibrillation, heart failure, stroke, or an episode of major bleeding during hospitalization for an ACS decreased significantly over time. Both in-hospital (2.1% in 1999; 1.3% in 2007) and 30-day multivariable-adjusted death rates decreased by more than 30% (odds ratio=0.66, 95% confidence interval=0.60-0.74) during the years under study. The hospital use of effective cardiac therapies (e.g. angiotensin-converting enzyme inhibitors, beta-blockers) increased significantly over time.

CONCLUSION: The results of this large observational study provide insights into the magnitude, changing characteristics, and short-term outcomes of comparatively young adults hospitalized with an ACS. Decreasing rates of short-term mortality and important clinical complications likely reflect enhanced treatment efforts that warrant future monitoring.

METHODS: The study population consisted of 59,032 patients hospitalized with an acute coronary syndrome at 113 sites in the Global Registry of Acute Coronary Events Study between 2000 and 2007.

RESULTS: A total of 4494 participants (7.6%) with acute coronary syndrome reported a history of atrial fibrillation and 3112 participants (5.3%) developed new-onset atrial fibrillation during their hospitalization. Rates of new-onset atrial fibrillation (5.5%-4.5%) and preexisting atrial fibrillation (7.4%-6.7%) declined during the study. Preexisting atrial fibrillation was associated with older age and greater cardiovascular disease burden, whereas new-onset atrial fibrillation was closely related to the severity of the index acute coronary syndrome. Patients with atrial fibrillation were less likely than patients without atrial fibrillation to receive evidence-based therapies and more likely to develop in-hospital complications, including heart failure. Overall hospital death rates in patients with new-onset and preexisting atrial fibrillation were 14.5% and 8.9%, respectively, compared with 1.2% in those without atrial fibrillation. Short-term death rates in patients with atrial fibrillation declined over the study period.

CONCLUSIONS: Despite a reduction in the rates of, and mortality from, atrial fibrillation, this arrhythmia exerts a significant adverse effect on survival among patients hospitalized with an acute coronary syndrome. Opportunities exist to improve the identification and treatment of patients with acute coronary syndrome with, or at risk for, atrial fibrillation to reduce the incidence and resultant complications of this dysrhythmia.

Copyright © 2012 Elsevier Inc. All rights reserved.

METHODS: The Global Registry of Acute Coronary Events (GRACE/GRACE2) and Canadian Registry of Acute Coronary Events (CANRACE) enrolled 14,285 patients across Canada between 1999 and 2008. Patients were stratified by the presence of history of AF. We compared clinical characteristics, medical therapies, cardiac procedures, and clinical outcomes between the 2 groups.

RESULTS: Overall, 1333 of the enrolled patients (9.3%) had history of AF, of whom 51.5% presented with non-ST-segment elevation myocardial infarction, 29.5% with unstable angina, and 19.1% with ST-segment elevation myocardial infarction. Compared with the group without, patients with a history of AF less frequently received evidence-based antiplatelet and antithrombin therapies, left ventricle ejection fraction assessment, and coronary angiography (all P < 0.001); they also had higher unadjusted rates of in-hospital death, myocardial (re)infarction, and heart failure. However, in multivariable analysis, history of AF was not found to be independently associated with in-hospital mortality (adjusted odds ratio [OR] = 1.12; 95% confidence interval (CI), 0.73-1.73; P = 0.61) or death and/or myocardial reinfarction (adjusted OR = 1.15; 95% CI, 0.87-1.5; P = 0.34).

CONCLUSIONS: History of AF is common among ACS patients. They received less evidence-based medical and invasive therapies than ACS patients without history of AF. History of AF is a negative independent predictor of in-hospital coronary angiography but was not found to be independently associated with adverse outcomes. All rights reserved.

METHODS: In 59,161 patients enrolled in the Global Registry of Acute Coronary Events Study between 2000 and 2007, we determined the incidence, prognosis, and factors associated with VF-CA.

RESULTS: Overall, 3618 patients (6.2%) developed VF-CA during their hospitalization for an ACS. Incidence rates of VF-CA declined over time. Patients who experienced VF-CA were on average older and had a greater burden of cardiovascular disease, yet were less likely to receive evidence-based cardiac therapies than patients in whom VF-CA did not occur. Hospital death rates were 55.3% and 1.5% in patients with and without VF-CA, respectively. There was a greater than 50% decline in the hospital death rates associated with VF-CA during the years under study. Patients with a VF-CA occurring after 48 h were at especially high risk for dying during hospitalization (82.8%).

CONCLUSION: Despite reductions in the magnitude of, and short-term mortality from, VF-CA, VF-CA continues to exert an adverse effect on survival among patients hospitalized with an ACS. Opportunities exist to improve the identification and treatment of ACS patients at risk for VF-CA to reduce the incidence of, and mortality from, this serious arrhythmic disturbance.

DESIGN AND SETTING: The Global Registry of Acute Coronary Events is a multinational, prospective, observational study involving 14 countries.

PATIENTS: Patients presenting to the hospital with a suspected ACS were stratified according to whether their predominant presenting symptoms included chest pain (ie, typical) or did not (ie, atypical). Demographics, medical history, hospital management, and outcomes were compared.

MEASUREMENTS AND RESULTS: Of the 20,881 patients in this analysis, 1,763 (8.4%) presented without chest pain, 23.8% of whom were not initially recognized as having an ACS. They were less likely to receive effective cardiac medications, and experienced greater hospital morbidity and mortality (13% vs 4.3%, respectively; p < 0.0001) than did patients with typical symptoms. After adjusting for potentially confounding variables, increased hospital mortality rates were noted in patients with dominant presenting symptoms of presyncope/syncope (odds ratio [OR], 2.0; 95% confidence interval [CI], 1.4 to 2.9), nausea or vomiting (OR, 1.6; 95% CI, 1.1 to 2.4), and dyspnea (OR, 1.4; 95% CI, 1.1 to 1.9), and in those with painless presentations of unstable angina (OR, 2.2; 95% CI, 1.4 to 3.5) and ST-segment elevation myocardial infarction (OR, 1.7; 95% CI, 1.2 to 2.2).

CONCLUSION: Patients with ACSs who present without chest pain are frequently misdiagnosed and undertreated. With the exception of diaphoresis, each dominant presenting symptom independently identifies a population that is at increased risk of dying. These patients experience greater morbidity and a higher mortality across the spectrum of ACSs.

METHODS: From 1999 to 2008, 14,196 Canadian patients with non-ST-segment elevation ACS were recruited into the Acute Coronary Syndrome I (ACSI), ACSII, Global Registry of Acute Coronary Events (GRACE/GRACE(2)), and Canadian Registry of Acute Coronary Events (CANRACE) prospective multicenter registries.

RESULTS: Women in the study population were found to be significantly older than men and were more likely to have a history of heart failure, diabetes, or hypertension. Fewer women were treated with thienopyridines, heparin, and glycoprotein IIb/IIIa inhibitors compared with men in GRACE and CANRACE. Female gender was independently associated with a lower in-hospital use of coronary angiography (adjusted odds ratio 0.76, 95% CI 0.69-0.84, P < .001) and higher in-hospital mortality (adjusted odds ratio 1.26, 95% CI 1.02-1.56, P = .036), irrespective of age (P for interaction =.76). Underestimation of patient risk was the most common reason for not pursuing an invasive strategy in both men and women.

CONCLUSIONS: Despite temporal increases in the use of invasive cardiac procedures, women with ACS are still more likely to be treated conservatively, which may be due to underestimation of patient risk. Furthermore, they have worse in-hospital outcomes. Greater awareness of this paradox may assist in bridging the gap between current guidelines and management practices.

METHODS: Of 4045 STEMI patients, 2024 received reperfusion therapy and had complete data on invasive management. They were stratified by reperfusion strategy used: primary percutaneous coronary intervention (PCI) (n =716); fibrinolysis with rescue PCI (n =177); fibrinolysis with urgent/elective PCI (n =210); and fibrinolysis without PCI (n =921). Data were collected on clinical and laboratory findings, and outcomes.

RESULTS: Compared with fibrinolytic-treated patients, patients treated with primary PCI were younger and had higher Killip class, had longer time to delivery of reperfusion therapy, and utilized more antiplatelet therapy but less heparin, beta-blockers and angiotensin-converting enzyme inhibitors. In-hospital death occurred in 2.7% of patients treated with primary PCI, 1.7% fibrinolysis-rescue PCI, 1.0% fibrinolysis-urgent/elective PCI, and 4.8% fibrinolysis-alone (P =0.009); the rates of death/reinfarction were 3.9%, 4.0%, 4.3%, and 7.1% (P =0.032), respectively. The rate of shock was highest in the primary PCI group. Rates of heart failure or major bleeding were similar in the 4 groups. In multivariable analysis, no PCI during hospitalization was associated with death and reinfarction (adjusted odds ratio = 1.66; 95% confidence interval, 1.03-2.70; P =0.04).

CONCLUSIONS: Clinical features, time to reperfusion, and medication utilization differed with respect to the reperfusion strategy. While low rates of re-infarction/death were observed, these complications occurred more frequently in those who did not undergo PCI during index hospitalization. Inc. All rights reserved.

METHODS: Using data from the Canadian Global Registry of Acute Coronary Events (GRACE), we stratified 14,090 ACS patients into 4 groups according to prior use of antithrombotic therapies and compared in-hospital management and outcomes.

RESULTS: Among 14,090 ACS patients, 7411 (52.6%) were not on prior ASA or warfarin therapy, 5724 (40.6%) were on ASA only, 593 (4.2%) were on warfarin only, and 362 (2.6%) were on both ASA and warfarin. ACS patients taking ASA and/or warfarin were older with more comorbidities than the patients on neither drug. Patients receiving prior warfarin only or ASA and warfarin were less likely to receive guideline-recommended therapies. Patients who were taking prior warfarin only had higher unadjusted rates of death, death and/or reinfarction (re-MI), congestive heart failure (CHF), and major bleeding as compared with patients on no prior therapy. Furthermore, patients who were taking ASA and warfarin had higher unadjusted rates of death and/or re-MI and CHF than patients on prior ASA only.

CONCLUSIONS: ACS patients on prior warfarin are a high-risk population, yet they receive less guideline-recommended therapies and have higher unadjusted adverse event rates during their index hospitalization. With the increasing use of oral anticoagulants, clinical trials are needed to guide the optimal management of these ACS patients. Inc. All rights reserved.

METHODS: A total of 18 cluster sites in 14 countries in North America, South America, Europe, Australia, and New Zealand are currently collaborating in GRACE. Clusters were chosen on the basis of local demographic characteristics and hospital facilities to ensure a representative sample of patients with ACS from each country. Patients are identified by use of either active or passive surveillance approaches. A standardized core case report form is completed for all patients. Information on patient demographics, medical history, acute symptoms, clinical characteristics, electrocardiographic findings, treatment approaches, and in-hospital outcomes is collected. Patients are followed up at 6 months after hospital discharge to identify recurrent coronary events, use of various medications, and mortality.

CONCLUSIONS: The information collected from the GRACE project will provide important and extensive insights into patient demographic and clinical characteristics, current practice patterns, and outcomes for patients with ACS from a number of countries throughout the world. Given the pressures of practicing evidence-based medicine, the results of GRACE should provide a multinational perspective into these important outcomes and identify practice variations that will allow new opportunities to improve patient care.

DESIGN: Multinational, prospective, observational study (GRACE, Global Registry of Acute Coronary Events).

SETTING: Patients hospitalised for a suspected acute coronary syndrome and enrolled in GRACE between April 1999 and December 2004.

PATIENTS: 29 039 patients with NSTE ACS.

MAIN OUTCOME MEASURES: Characteristics and outcomes were compared for trial-eligible (75.0%) and trial-ineligible (25.0%) patients.

RESULTS: GP IIb/IIIa inhibitors were administered to 20.0% of eligible and 15.3% of ineligible patients. Compared with eligible patients, ineligible patients who received GP IIb/IIIa inhibitors had significantly higher rates of hospital death (6.8% vs 3.7%) and major bleeding (4.9% vs 2.2%). After adjustment for their higher baseline risk, ineligible patients still experienced higher hospital death rates (adjusted odds ratio (OR) 1.60; 95% confidence interval (CI) 1.01 to 2.39), but not higher bleeding rates, than the eligible group. Use of GP IIb/IIIa inhibitors was associated with a trend towards lower 6-month mortality in eligible (OR 0.86, 95% CI 0.72 to 1.02) and ineligible (OR 0.82, 95% CI 0.65 to 1.05) patients compared with those in whom this therapy was not used.

CONCLUSIONS: GP IIb/IIIa inhibitors were markedly underused in the real-world population, irrespective of whether patients were trial-eligible or not. Despite the higher risk of ineligible patients, the benefits of GP IIb/IIIa inhibitors appear to be no less than in eligible patients.

DESIGN, SETTING AND PARTICIPANTS: Our analysis of the Australian and New Zealand cohort of the Global Registry of Acute Coronary Events (GRACE) included patients with ST-segment-elevation myocardial infarction (STEMI) and non-ST-segment-elevation ACS (NSTEACS) enrolled continuously between January 2000 and December 2007 from 11 metropolitan and rural centres in Australia and New Zealand.

RESULTS: 5615 patients were included in this analysis (1723 with STEMI; 3892 with NSTEACS). During 2000-2007 there was an increase in the use of statin therapy, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and thienopyridines (P < 0.0001 for each). Among patients with STEMI, there was an increase in emergency revascularisation with PCI (from 11% to 27% [P < 0.0001]), and inhospital coronary angiography (from 61% to 76% [P < 0.0001]). Among patients with NSTEACS, there was an increase in revascularisation with PCI (from 20% to 25% [P = 0.004]). Heart failure rates declined substantially among STEMI and NSTEACS patients (from 21% to 12% [P = 0.0002], and from 13% to 4% [P < 0.0001], respectively) as did rates of hospital readmission for ischaemic heart disease at 6 months (from 23% to 9% [P = 0.0001], and from 24% to 15% [P = 0.0001], respectively).

CONCLUSIONS: From 2000 to 2007 in Australia and New Zealand, there was a fall in inhospital events and 6-month readmissions among patients admitted with ACS. This showed an association with improved uptake of guideline-recommended medical and interventional therapies. These data suggest an overall improvement in the quality of care offered to contemporary ACS patients in Australia and New Zealand.