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Background: Approximately 50% of patients undergoing primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI) have multivessel coronary disease (MVD). Evidence on the best PCI approach for these patients is conflicting. The aim of this study is to examine Australian data from the CONCORDANCE registry to describe the practice and outcomes of patients receiving multivessel vs culprit-only PCI., Methods: Two cohorts were constructed from MVD-STEMI patients undergoing primary PCI at 41 hospitals between 2009 and 2015: culprit-only PCI (n = 587; 87%) and multivessel PCI (n = 82; 12%). Clinical characteristics were described, and the outcomes were all-cause mortality, heart failure, and myocardial reinfarction, in-hospital and at 6-month follow-up. The relative prevalence of each procedure over time was also described., Results: The patient cohorts were comparable in age, sex, and cardiovascular risk factors. Patients with higher Killip scores were more likely to receive multivessel PCI (P=.02). The multivessel group was significantly more likely to have in-hospital cardiogenic shock (P<.01), myocardial reinfarction (P=.02), cardiac arrest (P=.02), and stroke (P=.01). There was no difference in the incidence of ischemic events at 6 months, but the multivessel group had a lower rate of planned repeat revascularizations (12% vs 2%; P=.03). There was no difference in the relative frequency of multivessel vs culprit-only PCI during the observation period., Conclusions: The relative frequency of multivessel vs culprit-only PCI has not changed from 2009-2015. Index complete revascularization for STEMI-MVD patients is more likely to be performed in those with worse presentations and is associated with worse in-hospital complications.

Introduction: For non-ST-segment elevation acute coronary syndrome (NSTEACS) there is a gap between the use of class I guideline recommended therapies and clinical practice. The Global Registry of Acute Coronary Events (GRACE) risk score is recommended in international guidelines for the risk stratification of NSTEACS, but its impact on adherence to guideline-indicated treatments and reducing adverse clinical outcomes is unknown. The objective of the UK GRACE Risk Score Intervention Study (UKGRIS) trial is to assess the effectiveness of the GRACE risk score tool and associated treatment recommendations on the use of guideline-indicated care and clinical outcomes., Methods and Analysis: The UKGRIS, a parallel-group cluster randomised registry-based controlled trial, will allocate hospitals in a 1:1 ratio to manage NSTEACS by standard care or according to the GRACE risk score and associated international guidelines. UKGRIS will recruit a minimum of 3000 patients from at least 30 English National Health Service hospitals and collect healthcare data from national electronic health records. The co-primary endpoints are the use of guideline-indicated therapies, and the composite of cardiovascular death, non-fatal myocardial infarction, new onset heart failure hospitalisation or cardiovascular readmission at 12 months. Secondary endpoints include duration of inpatient hospital stay over 12 months, EQ-5D-5L responses and utilities, unscheduled revascularisation and the components of the composite endpoint over 12 months follow-up., Ethics and Dissemination: The study has ethical approval (North East - Tyne & Wear South Research Ethics Committee reference: 14/NE/1180). Findings will be announced at relevant conferences and published in peer-reviewed journals in line with the funder's open access policy., Trial Registration Number: ISRCTN29731761; Pre-results., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ.)

Background: Increased access to reperfusion for ST elevation myocardial infarction (STEMI) has contributed to reduced mortality internationally. We describe temporal trends in pre-hospital care, in-hospital management and outcomes of the STEMI population in Australia., Methods: Temporal trends with multiple regression analysis on the management and outcomes of STEMI patients enrolled across 46 Australian hospitals in the Australian cohort of the Global Registry of Acute Coronary Events (GRACE) and the Cooperative National Registry of Acute Coronary Care Guideline Adherence and Clinical Events (CONCORDANCE) between February 1999 and August 2016., Results: 4,110 patients were treated for STEMI, mean age 62.5±13.7years (SD). The median door-to-balloon time of primary percutaneous coronary intervention (PPCI) decreased by 11minutes (p<0.01) although there was no increase in rates of PPCI (p=0.35). Access to non-primary PCI increased by 39% (p<0.01), provisioning of fibrinolysis decreased by 13% (p<0.01) and the median door-to-needle time of 35minutes remained unchanged (p=0.09). Prescription of medical therapies in-hospital remained high, and at discharge there was an increase in prescription of statins (p<0.01); aspirin including antiplatelets (p<0.01), beta blockers (p=0.023) and ACE/ARB (p=0.02). The occurrence of any in-hospital adverse clinical events declined by 78% (p<0.01) albeit, there was no reduction in mortality in-hospital (p=0.84) or within 6 months (p=0.81)., Conclusions: Over time, there has been increased access to non-primary PCI; shorter door-to-balloon times for PPCI; less adverse events in-hospital and fewer readmissions for unplanned revascularisation without the realisation of reduced mortality in-hospital or at 6 months., Trial Registration: CONCORDANCE Registry ACTRN: 12614000887673., (Copyright © 2018 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). All rights reserved.)

Background: Pulse pressure is a readily available vital sign that has been shown to independently predict outcomes in several cardiovascular disease states. We investigated the prognostic significance of pulse pressure (PP) and systolic blood pressure (SBP) among patients with acute coronary syndromes (ACS)., Methods: A total of 14,514 patients with ACS in the prospective, multicentre Global Registry of Acute Coronary Events (GRACE), expanded GRACE (GRACE-2) and Canadian Registry of Acute Coronary Events (CANRACE) were stratified by initial PP on presentation. Patient characteristics and in-hospital outcomes were compared by PP quartiles and the independent prognostic significance of PP for in-hospital mortality was quantified. We compared the discriminative ability (c-statistic) of models incorporating either PP or SBP., Results: Patients with higher PPs were older, more frequently female and had higher prevalence rates of conventional cardiovascular risk factors (all p  < 0.01). Lower PP was associated with ST-segment elevation myocardial infarction presentation, higher GRACE risk scores and higher rates of adverse in-hospital outcomes ( p  < 0.001). PP was strongly correlated with SBP (Pearson's correlation coefficient = 0.79, p  < 0.001). After adjustment for other GRACE risk model predictors, lower PP was independently associated with in-hospital mortality (first vs. fourth quartile [reference]: adjusted odds ratio 2.57, 95% confidence interval 1.80-3.67). The c-statistic was slightly higher for the multivariable model incorporating SBP as compared to the model with PP (0.868 vs. 0.864, respectively, p  = 0.028) for in-hospital mortality., Conclusion: Higher presenting PP is associated with increased age and more prevalent cardiovascular risk factors, whereas patients with lower PP present with worse clinical characteristics and in-hospital outcomes. Lower PP is an independent adverse prognosticator in ACS. However, PP did not improve the discriminatory performance of the GRACE risk score compared with SBP.

Background: Socioeconomic status (SES) is a social determinant of both health and receipt of health care services, but its impact is under-studied in acute coronary syndrome (ACS). The aim of this study was to examine the influence of SES on in-hospital care, and clinical events for patients presenting with an ACS to public hospitals in Australia., Methods: Data from 9064 ACS patient records were collected from 41 public hospitals nationwide from 2009 as part of the Cooperative National Registry of Acute Coronary Syndrome Care (CONCORDANCE) registry. For this analysis, we divided the cohort into four socioeconomic groups (based on postcode of usual residence) and compared the in-hospital care provided and clinical outcomes before and after adjustment for both patient clinical characteristics and hospital clustering., Results: Patients were divided into four SES groups (from the most to the least disadvantaged: 2042 (23%) vs. 2104 (23%) vs. 1994 (22%) vs. 2968 (32%)). Following adjustments for patient characteristics, there were no differences in the odds of receiving coronary angiogram, revascularisation, prescription of recommended medication, or referral to cardiac rehabilitation across the SES groups (p=0.06, 0.69, 0.89 and 0.79, respectively). After adjustment for clinical characteristics, no associations were observed for in-hospital and cumulative death (p=0.62 and p=0.71, respectively). However, the most disadvantaged group were 37% more likely to have a major adverse cardiovascular event (MACE) than the least disadvantaged group (OR (95% CI): 1.37 (1.1, 1.71), p=0.02) driven by incidence of in-hospital heart failure., Conclusions: Although there may be gaps in the delivery of care, this delivery of care does not differ by patient's SES. It is an encouraging affirmation that all patients in Australian public hospitals receive equal in-hospital care, and the likelihood of death is comparable between the SES groups., (Copyright © 2017 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.)

Aims: There is little information on clinical risk stratification (CRS) compared to objective risk tools in patients with non-ST elevation acute coronary syndromes (NSTEACS). We quantified CRS use, its agreement with Global Registry of Acute Coronary Events (GRACE) risk scores (GRS), and association with outcomes., Methods and Results: Data were extracted from the Australian Cooperative National Registry of Acute Coronary Care, Guideline Adherence and Clinical Events (CONCORDANCE), a multi-centre NSTEACS registry. From February 2009 to December 2015, 4512 patients from 41 sites were included. Predictors of CRS use and association with treatment were identified, CRS-GRS agreement determined and prediction of in-hospital and 6-month mortality compared. Clinical risk stratification was documented in 21% of patients. Family history of coronary disease was the only independent predictor of CRS use [odds ratio (OR) 1.23, 95% confidence interval (95% CI) 1.04-1.45]; electrocardiogram changes (OR 0.8, 95% CI 0.68-0.96), elevated biomarkers (OR 0.59, 95% CI 0.48-0.73), dementia (OR 0.56, 95% CI 0.36-0.84), and an urban hospital setting (OR 0.41, 95% CI 0.19-0.89) were independent negative predictors. A treatment-risk paradox was observed: high CRS risk patients received less anticoagulation (79% vs. 88%, P = 0.001) and angiography (83% vs. 71%, P < 0.001). CRS-GRS agreement was poor (kappa coefficient = 0.034) and CRS less predictive for in-hospital (c-statistic 0.54 vs. 0.87, P < 0.001) and 6-month (c-statistic 0.55 vs. 0.74, P < 0.01) mortality., Conclusion: In Australia, CRS does not guide treatment, correlate with GRS or predict outcomes. This study suggests the need for greater awareness and integration of validated tools such as the GRACE score to optimally direct treatment and potentially improve outcomes.

Background Little is known about the prognostic implications of frailty, a state of susceptibility to stressors and poor recovery to homeostasis in older people, after myocardial infarction ( MI ). Methods and Results We studied 3944 MI patients aged ≥65 years treated at 41 Australian hospitals from 2009 to 2016 in the CONCORDANCE ( Australian Cooperative National Registry of Acute Coronary Care, Guideline Adherence and Clinical Events ) registry. Frailty index ( FI ) was determined using the health deficit accumulation method. All-cause and cardiac-specific mortality at 6 months were compared between frail ( FI >0.25) and nonfrail ( FI ≤0.25) patients. Among 1275 patients with ST-segment-elevation MI (STEMI), 192 (15%) were frail, and among 2669 non-STEMI ( NSTEMI) patients, 902 (34%) were frail. Compared with nonfrail counterparts, frail STEMI patients received 30% less reperfusion therapy and 22% less revascularization during index hospitalization; frail NSTEMI patients received 30% less diagnostic angiography and 39% less revascularization. Unadjusted 6-month all-cause mortality ( STEMI : 13% versus 3%; NSTEMI : 13% versus 4%) and cardiac-specific mortality ( STEMI : 6% versus 1.4%, NSTEMI : 3.2% versus 1.2%) were higher among frail patients. After adjustment for known prognosticators, FI was significantly associated with higher 6-month all-cause ( STEMI : odds ratio: 1.74 per 0.1 FI [ 95% confidence interval, 1.37-2.22], P<0.001; NSTEMI : odds ratio: 1.62 per 0.1 FI [95% confidence interval, 1.40-1.87], P<0.001) but not cardiac-specific mortality ( STEMI : P=0.99; NSTEMI : P=0.93). Conclusions Frail patients receive lower rates of invasive cardiac care during MI hospitalization. Increased frailty was independently associated with increased postdischarge all-cause mortality but not cardiac-specific mortality. These findings inform identification of frailty during MI hospitalization as a potential opportunity to address competing risks for mortality in this high-risk population.

Background: Despite being recommended in acute coronary syndrome (ACS) guidelines, the use of invasive management within specific risk groups continues to be debated. This study examines the change in the use of invasive management in ACS by patient risk and the associated change in mortality within Australia over the last 17 years., Methods: Pooled cohorts derived from five ACS registries (ACACIA, CONCORDANCE, GRACE, Snapshot-ACS, and Predict) spanned from 1999 to 2015. After excluding patients without a final diagnosis of ACS (n = 4460), enrolled outside Australia (n = 1477) and without an enrolling year (n = 4), 15 912 patients were analysed. Data was stratified across three time periods (1999-2004, 2005-2009, and 2010-2015) using clinical risk characteristics (age, ACS diagnosis, biomarker elevation, and GRACE score) to monitor change in practice., Results: Over the 17-year period, the use of invasive management increased (4073/6863 (59.3%) cases [1999-2009] vs. 6670/8706 (76.6%) cases [2010-2015]). Invasive management accounted for improvements in mortality in intermediate- and high-risk groups (intermediate risk: 14% (95% CI 1-66%) [1999-2009] vs. 49% (95% CI 2-59%) [2010-2015]; high risk: 24% (95% CI 6-42%) [1999-2009] vs. 48% (95% CI 19-76%) [2010-2015]). Patients receiving no angiography compared with interventional management had worse outcomes (1999-2004 1.55 HR [95% CI 1.36-1.80], P < 0.0001 vs. 2010-2015 1.90 HR [95% CI 1.45-2.51], P < 0.0001)., Conclusions: Clinical practice in ACS has changed over the last 17 years with positive outcomes seen with invasive management among high-risk patients. Unfortunately, a considerable burden of mortality remains in patients managed medically, highlighting a need for more focused strategies that improve care and outcomes in this group., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.)

Aims: Acute coronary syndrome (ACS) is a costly condition for health service provision yet variation in the delivery of care between hospitals persists. A composite measure of adherence with evidence-based clinical-process indicators (CPIs) could better inform hospital performance reporting and clinical outcomes in the management of ACS., Methods: Data on 7444 ACS patients from 39 Australian hospitals were used to derive a hospital-specific composite quality score by calculating mean adherence to 14 evidence-based CPIs. Using the generalized estimating equation to account for clustering of patients within hospitals and the GRACE risk score to adjust for differences in presenting risk, we evaluated associations between the hospital-specific composite quality score, in-hospital major adverse events, in-hospital mortality and mortality and readmission for ACS at 6 months., Results: Hospitals had a mean adherence of 68.3% (SD 21.7) with the composite quality score. There was significant variation between hospital adherence tertile 1 (79%) and tertile 3 (56%), P < 0.0001. With risk adjustment, there was an association between hospitals with a higher composite quality score and reduced in-hospital adverse events (OR: 0.85, CI: 0.71-0.99) and survival at hospital discharge (OR: 0.47; 95% CI: 0.28-0.77). There was trending improvement in survival at 6 months (OR 0.48; CI: 0.20-1.16) and fewer readmissions to hospital for ACS at 6 months (OR 0.79; CI 0.60-1.05)., Conclusion: The association between the quality composite score and reduced in-hospital events and survival at hospital discharge supports the utility of reporting CPIs in routine hospital performance reporting on the management of ACS., Australia and New Zealand Clinical Trial Registration (anzctr): CONCORDANCE Registry ACTRN12614000887673., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.)

We examined the relations between right bundle branch block (RBBB) and clinical characteristics, management, and outcomes among a broad spectrum of patients with acute coronary syndrome (ACS). Admission electrocardiograms of patients enrolled in the Global Registry of Acute Coronary Events (GRACE) electrocardiogram substudy and the Canadian ACS Registry I were analyzed independently at a blinded core laboratory. We performed multivariable logistic regression analysis to assess the independent prognostic significance of admission RBBB on in-hospital and 6-month mortality. Of 11,830 eligible patients with ACS (mean age 65; 66% non-ST-elevation ACS), 5% had RBBB. RBBB on admission was associated with older age, male sex, more cardiovascular risk factors, worse Killip class, and higher GRACE risk score (all p <0.01). Patients with RBBB less frequently received in-hospital cardiac catheterization, coronary revascularization, or reperfusion therapy (all p <0.05). The RBBB group had higher unadjusted in-hospital (8.8% vs 3.8%, p <0.001) and 6-month mortality rates (15.1% vs 7.6%, p <0.001). After adjusting for established prognostic factors in the GRACE risk score, RBBB was a significant independent predictor of in-hospital death (odds ratio 1.45, 95% CI 1.02 to 2.07, p = 0.039), but not cumulative 6-month mortality (odds ratio 1.29, 95% CI 0.95 to 1.74, p = 0.098). There was no significant interaction between RBBB and the type of ACS for either in-hospital or 6-month mortality (both p >0.50). In conclusion, across a spectrum of ACS, RBBB was associated with preexisting cardiovascular disease, high-risk clinical features, fewer cardiac interventions, and worse unadjusted outcomes. After adjusting for components of the GRACE risk score, RBBB was a significant independent predictor of early mortality., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Cohort studies of STEMI patients have reported that over 30% receive no reperfusion. Barriers to greater use of reperfusion in STEMI patients require further elucidation., Methods: We collected data on STEMI patients with no reperfusion as part of the SNAPSHOT ACS Registry, which recruited consecutive ACS patients in 478 hospitals throughout Australia and New Zealand during 14-27 May 2012., Results: Of 4387 patients enrolled, 419 were diagnosed with STEMI. Primary PCI (PPCI) was performed in 160 (38.2%), fibrinolysis was used in 105 (25.1%), and 154 (36.7%) had no reperfusion. Patients with no reperfusion had a mean age of 70.3±15.0 years compared with 63.1±13.5 in the reperfusion group (p<0.0001). There were more females in the no reperfusion group (37.1% v 23.0% p=0.002) and they were significantly more likely to have prior PCI or CABG, heart failure, atrial fibrillation, chronic kidney disease and other vascular disease, and to be nursing home residents (all p<0.05). Patients without reperfusion had a significantly higher mortality in hospital (11.7% v 4.9%, p=0.011). In 370 patients who presented within 12hours, 28 had early angiography without PCI, which was considered an attempt at reperfusion. Therefore reperfusion was attempted in 293 of 370 eligible patients (79.2%)., Conclusion: Of consecutive STEMI patients, 36.7% did not receive any reperfusion and they had a higher risk of death in hospital. In eligible patients, reperfusion was attempted in 79.2%. National strategies to encourage earlier medical contact and greater use of reperfusion in eligible patients may lead to better outcomes., (Copyright © 2015 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.)

Background: Assessing risk and weighing the potential benefits from evidence-based therapies are essential in the clinical decision making process of optimizing care and outcomes for patients presenting with acute coronary syndromes (ACS). Such practices are advocated in international clinical guidelines of ACS care. While the GRACE risk score (GRS) is a guideline advocated, well-validated risk stratification tool, its utility in improving care and outcomes remains unproven, and its application has been limited in routine clinical practice., Objective: This study will assess the effectiveness using the GRS tool and treatment recommendations during patient assessment on improving the application of guideline-recommended therapies in ACS care., Design: This study employs a PROBE (prospective cluster [hospital-level] randomized open-label, blinded endpoint) design to evaluate objective measures of hospital performance, with clinical events adjudicated by a blinded event committee. This randomized study is nested within the established CONCORDANCE registry of ACS patients, with existing methods for data collection and monitoring of care and clinical outcomes. The hospital-level intervention is the integration of the GRS into routine ACS patient assessment process. The study will assess the use of early invasive management, prescription of guideline recommended pharmacology and referral to cardiac rehabilitation by hospital discharge; with the key composite clinical endpoint of cardiovascular death, new or recurrent myocardial infarction, in-hospital heart failure or cardiovascular readmission at 12 months. Health economic impacts of risk stratification implementation will also be evaluated. The study will recruit 3000 patients from 30 hospitals., Summary: The AGRIS trial will establish the effect of routine objective risk stratification using the GRACE risk score on ACS care and clinical outcomes., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Purpose: Short-term outcomes have been well characterized in acute coronary syndromes; however, longer-term follow-up for the entire spectrum of these patients, including ST-segment-elevation myocardial infarction, non-ST-segment-elevation myocardial infarction, and unstable angina, is more limited. Therefore, we describe the longer-term outcomes, procedures, and medication use in Global Registry of Acute Coronary Events (GRACE) hospital survivors undergoing 6-month and 2-year follow-up, and the performance of the discharge GRACE risk score in predicting 2-year mortality., Methods: Between 1999 and 2007, 70,395 patients with a suspected acute coronary syndrome were enrolled. In 2004, 2-year prospective follow-up was undertaken in those with a discharge acute coronary syndrome diagnosis in 57 sites., Results: From 2004 to 2007, 19,122 (87.2%) patients underwent follow-up; by 2 years postdischarge, 14.3% underwent angiography, 8.7% percutaneous coronary intervention, 2.0% coronary bypass surgery, and 24.2% were re-hospitalized. In patients with 2-year follow-up, acetylsalicylic acid (88.7%), beta-blocker (80.4%), renin-angiotensin system inhibitor (69.8%), and statin (80.2%) therapy was used. Heart failure occurred in 6.3%, (re)infarction in 4.4%, and death in 7.1%. Discharge-to-6-month GRACE risk score was highly predictive of all-cause mortality at 2 years (c-statistic 0.80)., Conclusion: In this large multinational cohort of acute coronary syndrome patients, there were important later adverse consequences, including frequent morbidity and mortality. These findings were seen in the context of additional coronary procedures and despite continued use of evidence-based therapies in a high proportion of patients. The discriminative accuracy of the GRACE risk score in hospital survivors for predicting longer-term mortality was maintained., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: As there are limited data evaluating "clinical intuition" in risk prediction among acute coronary syndromes (ACS) patients. We evaluated the relationship between perceived and "scored" risk in ACS patients, and their association with care and outcome., Methods and Results: Within a prospective multi-center international ACS study from 58 hospitals in Australia, China, India and Russia enrolling patients between May 2009 and February 2011, at least 2 physicians involved in each patient's care estimated the patient's untreated risk, and the change in risk with invasive management. The association between clinical factors and physician perceived risk was assessed with multilevel mixed-effects regression models. Risk underestimation was defined as when physician-predicted risk was lower than GRACE score calculated risk and was used to compare clinical care and 6 month mortality. In total, 1542 patients and 4230 patient-specific physicians' estimates were obtained. By 6 months 48/1542 (3.1%) of patients had died compared with an estimated rate of 2.5% with full treatment. Advanced age, hypotension, tachycardia and ST changes on ECG were associated with increased perceived risk, while female gender was associated with lower perceived risk. Clinician risk underestimation was associated with less guideline therapy and higher 6-month mortality (not underestimated: 10/967 (1.0%) vs. one physician underestimated: 25/429 (5.8%) vs. all physician's underestimated: 13/146 (8.9%), any underestimation vs. no underestimation adjusted OR: 6.0 [95% CI: 2.3-15.5, p<0.001])., Conclusions: Clinical risk prediction using established risk characteristics is not consistently observed in clinical practice. Studies evaluating the implementation and outcomes associated with objective risk prediction are warranted., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Purpose of Review: Registries are becoming an increasingly important component of clinical practice through the collection of clinical data including outcomes on representative populations of patients. An understanding of registry structure and function is important for practicing cardiovascular clinicians. Clinical populations may be identified on the basis of procedures they undergo (procedural registries), or their clinical condition (disease registries). Registries provide opportunities to document and improve quality of care. They also provide insights into the nature of disease and the benefit of treatments in subgroups of patients, and poorly resourced environments, that are not well represented in randomized clinical trials., Recent Findings: To maximize the value of registries, minimum quality criteria must be met. These include clear definitions of the included populations, an unbiased inclusive patient sampling strategy, high quality data with processes to ensure this, a clear governance structure, and adherence to relevant ethical and privacy guidelines. Statistical techniques adjusting for the nonrandomized nature of treatment allocations continue to evolve. There is increasing potential for randomized controlled trials to be conducted within registry cohorts. By using the same clinical data for both the registry and the trial, and enrolling unselected patients, this cost-effective approach provides information on the effectiveness of care in the pragmatic clinical environment., Summary: The potential of these rich clinical data sources is yet to be realized. Future developments that will enhance their value include improved efficiencies by integration with the electronic medical record, more widespread crosstalk between high quality registries facilitated by data linkage, simplification of ethical processes, and development of sustainable funding models.

The early diagnosis of acute coronary syndrome (ACS) remains challenging, and a considerable proportion of patients are diagnosed with "possible" ACS on admission. The Global Registry of Acute Coronary Events (GRACE/GRACE(2)) and Canadian Registry of Acute Coronary Events (CANRACE) enrolled 16,618 Canadian patients with suspected ACS in 1999 to 2008. We compared the demographic and clinical characteristics, use of cardiac procedures, prognostic accuracy of the GRACE risk score, and in-hospital outcomes between patients given an admission diagnosis of "definite" versus "possible" ACS by the treating physician. Overall, 11,152 and 5,466 patients were given an initial diagnosis of "definite" ACS and "possible" ACS, respectively. Patients with a "possible" ACS had higher GRACE risk score (median 130 vs 125) and less frequently received aspirin, clopidogrel, heparin, or β blockers within the first 24 hours of presentation and assessment of left ventricular function, stress testing, cardiac catheterization, and percutaneous coronary intervention (all p <0.05). Patients with "possible" ACS had greater rates of in-hospital myocardial infarction (9.0% vs 2.0%, p <0.05) and heart failure (12% vs 8.9%, p <0.05). The GRACE risk score demonstrated excellent discrimination for in-hospital mortality in both groups and for the entire study population. In conclusion, compared to patients with "definite" ACS on presentation, those with "possible" ACS had higher baseline GRACE risk scores but less frequently received evidence-based medical therapies within 24 hours of admission or underwent cardiac procedures during hospitalization. The GRACE risk score provided accurate risk assessment, regardless of the initial diagnostic impression., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: Readmission following an acute coronary syndrome (ACS) is frequent in our community. Patient specific factors identifying those at risk of readmission are poorly described., Methods: Data were analysed from 5219 patients with an ACS enrolled in the Australian and New Zealand population of the Global Registry of Acute Coronary Events (GRACE) between 1999 and 2007. Patients who were readmitted for cardiovascular disease within 6 months of discharge were identified; regression analysis was used to predict independent patient factors associated with readmission 1 month and 1-6 months after discharge., Results: 1048 patients (20.1%) were readmitted within 6 months, with a significant proportion (n=434, 41.4%) of readmissions occurring within 30 days of discharge. Readmission within 6 months was associated with a higher incidence of unscheduled cardiac catheterisation (HR 25.64, 95% CI 18.41 to 35.71), unscheduled percutaneous coronary intervention (PCI) (HR 15.78, 95% CI 10.56 to 23.59), stroke (HR 1.92, 95% CI 1.08 to 3.43), and death (HR 2.40, 95% CI 1.66 to 3.49). Recurrent ischemia in hospital and a diagnosis of S-T elevation myocardial infarction during the index admission were associated with the strongest risk of early rehospitalisation, while revascularisation by PCI or coronary artery bypass surgery (CABG) was associated with lowest risk of early readmission. A history of heart failure, prior myocardial infarction or angina was associated with a greater likelihood of later rehospitalisation, whereas revascularisation by CABG was associated with the lowest risk of later rehospitalisation., Conclusions: Several patient and clinical factors identify patients at higher risk of readmission. Identifying these factors and escalating in-hospital and post-discharge care for these higher risk patients may prevent readmission and improve outcome.

Background: There are limited recent data on the prevalence and potentially different adverse impact of the various types of recurrent ischemia (RI) in unselected patients with acute coronary syndromes(ACS). We examined the clinical features and treatment associated with, and the differential prognostic impact of, the various types of RI in unselected patients across the broad spectrum of ACS in the contemporary era., Methods: The Global Registry of Acute Coronary Events (GRACE) was a prospective, multinational registry of patients hospitalized for ACS. Data were collected on standardized case report forms., Results: Of the 29,400 ACS patients enrolled in May 2000-March 2007, 21% developed RI; 2.4%, 4.9%, and 16% had myocardial (re-)infarction [(re-)MI], RI with ST-segment changes, and RI without ST-segment changes (not mutually exclusive), respectively. Rates of in-hospital mortality and complications, and 6-month mortality were significantly higher among patients with RI compared to those without; the rates were highest for patients who developed (re-)MI, followed by those with RI and ST-segment changes. After adjusting for other validated prognosticators in the GRACE risk score, all three types of RI retained an independent association with both higher in-hospital and post-discharge 6-month mortality. Early revascularization was associated with lower in-hospital mortality only in the group with (re-)MI (P for interaction=0.003)., Conclusions: Despite the current use of intensive medical therapies, RI remains a common and serious consequence across the spectrum of ACS. Different types of RI confer a variable adverse prognostic impact. Re-MI is associated with the worst outcome, which appears to be mitigated by early revascularization. Our findings underscore the persistent need to improve the treatment of ACS., (Copyright © 2009 Elsevier Ireland Ltd. All rights reserved.)

Background: Smoking induces CYP1A2, thereby enhancing clopidogrel conversion to its active metabolite. We sought to determine the association between clopidogrel use and clinical outcomes in smokers versus nonsmokers with a broad spectrum of acute coronary syndrome (ACS)., Methods: We examined the association between early clopidogrel use in-hospital and 6-month outcomes among 44,426 patients with ACS in relation to smoking status in the Global Registry of Acute Coronary Events. We tested for heterogeneity of clopidogrel effect among smokers versus nonsmokers in separate multivariable models that adjusted for (1) established prognosticators in the Global Registry of Acute Coronary Events risk score and (2) independent predictors of major bleeding., Results: Rates of in-hospital mortality, death/myocardial infarction, and major bleeding were 4.3%, 5.9%, and 2.5%, respectively. Current smokers (n = 12,149) were more likely to be younger men without documented vascular disease; had lower rates of hypertension, hyperlipidemia, and diabetes; and more frequently presented with ST elevation (all P < .0001). Early clopidogrel use (55%) was associated with a reduction in the composite endpoint of mortality and myocardial infarction both in-hospital and at 6 months among current smokers and nonsmokers. There was no interaction between current smoking and clopidogrel use for ischemic endpoints. Major bleeding associated with early clopidogrel use was actually lower among current smokers compared with nonsmokers., Conclusions: Despite prior observations of smoking-enhanced clopidogrel effects, early clopidogrel use among smokers presenting with ACS compared with nonsmokers was not independently associated with a greater reduction in cardiovascular events. In contrast with nonsmokers, clopidogrel use among smokers was not associated with excess bleeding, perhaps because of unmeasured confounders., (Copyright © 2010 Mosby, Inc. All rights reserved.)

Objectives: The purpose of this study is to evaluate hospital mortality and major bleeding rates among patients receiving low molecular weight heparin (LMWH), unfractionated heparin (UFH), or both, and to investigate whether concomitant glycoprotein (GP) IIb/IIIa antagonists and coronary intervention affect patterns of use and outcomes with different heparins., Background: With widespread use of glycoprotein (GP) IIb/IIIa inhibitors and invasive treatments, patients with high-risk acute coronary syndrome (ACS) may have a greater bleeding risk and may not gain additional benefit from LMWHs. The purpose of this study is to evaluate hospital mortality and major bleeding rates among patients receiving LMWH, UFH, or both, and to investigate whether concomitant GP IIb/IIIa antagonists and coronary intervention affect patterns of use and outcomes with different heparins., Methods: Data were analyzed from 28,445 patients with ACS; 21,287 had non-ST-segment elevation myocardial infarction or unstable angina and received LMWH or UFH., Results: Fifty-one percent of patients received LMWH, 32% UFH, and 17% both. The lowest inhospital mortality and bleeding rates occurred with LMWH (2.7% and 1.8% vs UFH, 4.1% and 2.7%; all P < .0001). After multivariable analysis, LMWH was associated with lower inhospital mortality rates in patients not treated with GP IIb/IIIa antagonists, irrespective of whether they had a percutaneous coronary intervention (PCI) (odds ratio 0.77, 95% confidence interval 0.63-0.94 without PCI vs odds ratio 0.45, 95% confidence interval 0.21-0.98 with PCI). Excess bleeding occurred with PCI in LMWH-treated patients. Patients older than 75 years who received GP IIb/IIIa antagonists and any antithrombotic but not PCI had an increased risk of major bleeding (LMWH 14%, UFH 8.3%)., Conclusions: In patients with non-ST-elevation ACS without GP IIb/IIIa antagonists, LMWH was associated with a lower mortality rate and more bleeding episodes in PCI-treated patients than UFH; no differences occurred with GP IIb/IIIa antagonists. Elderly patients managed medically with GP IIb/IIIa antagonists and either heparin had a very high major bleeding risk.

Background: There are limited data describing the presenting characteristics, management, and outcomes of diabetic and nondiabetic patients with an acute coronary syndrome (ACS)., Objective: To examine differences in these factors, patients with ST-segment elevation acute myocardial infarction, non-ST-segment elevation acute myocardial infarction, and unstable angina were enrolled in a large multinational coronary disease registry., Methods: The Global Registry of Acute Coronary Events is a prospective observational study of patients hospitalized with an ACS at 94 hospitals in 14 countries. The study sample consisted of 5403 patients with ST-segment elevation acute myocardial infarction, 4725 with non-ST-segment elevation acute myocardial infarction, and 5988 with unstable angina., Results: Approximately 1 in 4 patients presented to participating hospitals with a history of diabetes. Patients with diabetes were older, more often women, with a greater prevalence of comorbidities, and they were less likely to be treated with effective cardiac therapies than nondiabetic patients. Patients with diabetes who developed an ACS were at increased risk for each hospital outcome examined including heart failure, renal failure, cardiogenic shock, and death. These differences remained after adjustment for potentially confounding prognostic factors., Conclusions: A considerable proportion of patients with an ACS has diabetes and is at increased risk for adverse outcomes compared with patients without diabetes. There are certain proven therapeutic strategies that remain underused in the diabetic population. A more widespread awareness of this increased risk and a more diligent use of proven cardiac treatment approaches are indicated for patients with diabetes who develop an ACS.

Relatively limited data are available, particularly from the perspective of a multinational registry, about the post-discharge outcomes and management practices of patients with an acute coronary syndrome (ACS). The objectives of this longitudinal study were to examine 6-month outcomes in a large multinational sample of patients hospitalized with an ACS. A total of 5,476 patients with ST-segment elevation acute myocardial infarction (STEAMI), 5,209 patients with non-ST-segment elevation acute myocardial infarction (NSTEAMI), and 6,149 patients with unstable angina pectoris discharged from 90 hospitals in 14 countries comprised the study population. The study sample was recruited from 18 cluster sites in 14 countries that are currently collaborating in the Global Registry of Acute Coronary Events (GRACE) study. The 6-month post-discharge death rates were 4.8% in patients with STEAMI, 6.2% in patients with NSTEAMI, and 3.6% in patients with unstable angina pectoris. Approximately 1 in 5 of each of our comparison groups were rehospitalized for heart disease during the 6-month follow-up, and approximately 15% of each of the respective study cohorts underwent coronary revascularization during follow-up. Demographic and clinical characteristics of post-discharge decedents were identified according to type of ACS. Our results suggest that a considerable proportion of patients who were discharged from the hospital after an ACS, with some differences noted according to type of ACS, remain at increased risk for adverse outcomes during the relatively brief post-discharge period. These data suggest the need for better long-term medical management and more intense follow-up of patients with an ACS to improve their long-term outlook.

Aims: Despite advances in the treatment of acute coronary syndromes based on randomized trial data and published guidelines, the extent to which such treatments are applied in practice remains uncertain. Data from clinical trials derive from selected geographical areas and in highly selected populations of patients, and hence may not reflect the overall population. The aim of the study was to investigate variations in hospital management and outcome using unselected data collected in the prospective Global Registry of Acute Coronary Events (GRACE)., Methods and Results: The 95 hospitals in GRACE were organized into 18 population-based clusters in 14 countries. Information was recorded about patient management and outcome during hospitalization and after discharge. Data on treatments administered were analysed by baseline condition, hospital type, by the presence or absence of a catheterization laboratory, and by geographical region. Of 11543 patients, 44% had an admission diagnosis of unstable angina, 36% presented with myocardial infarction, 9% were admitted to rule out a myocardial infarction, 7% had chest pain and 4% were hospitalized for 'other cardiac' and 'non-cardiac' diagnoses. Of the total GRACE population 38% had a final diagnosis of unstable angina, 30% ST-segment elevation myocardial infarction, 25% non-ST-segment elevation myocardial infarction, and 7% of 'other cardiac' and 'non-cardiac' final diagnoses. The event rates for hospital death or reinfarction were six and 2% for non-ST-segment elevation myocardial infarction, seven and 3% for ST-segment elevation myocardial infarction, and 3% hospital death for unstable angina. The use of aspirin was similar across all hospital types and geographical regions. In contrast, the use of percutaneous coronary intervention and glycoprotein IIb/IIIa inhibitors was higher (P<0.0001) in teaching hospitals and hospitals with catheterization laboratories and was also higher in the United States. At discharge a higher percentage (P<0.0001) of patients received angiotensin-converting enzyme inhibitors in hospitals without catheterization laboratories. The use of statins was lower in non-teaching hospitals and in centres without a catheterization laboratory., Conclusions: The GRACE study reveals substantial differences in the management of patients based on hospital type and geographical location. Further analyses will determine whether such variations translate into differences in longer term outcomes. GRACE provides a multinational reference for the implementation of therapies of proven efficacy., (Copyright 2002 The European Society of Cardiology. Published by Elsevier Science Ltd. All rights reserved.)

Background: The American College of Cardiology (ACC)/American Heart Association (AHA) guidelines for exercise testing suggest that only selected groups of high-risk patients should undergo routine functional testing after percutaneous transluminal coronary angioplasty (PTCA) for the detection of restenosis., Objectives: Our purpose was (1) to document the patterns of use of post-PTCA functional testing and (2) to determine whether the choice of functional testing strategy is related to clinical characteristics of patients or whether physicians use a similar strategy for all their patients., Methods: The Routine Versus Selective Exercise Treadmill Testing After Angioplasty (ROSETTA) Registry is a prospective study examining the use of functional testing among 788 patients at 13 centers in 5 countries., Results: During the 6-month period after a successful PTCA, 49% of patients underwent functional testing (range among centers 10%-81%). Among patients who underwent functional testing, 39% had a clinical indication and 61% had functional testing as a routine follow-up. The first functional test was performed a median of 7 weeks after PTCA, with 13% of patients having second tests at a median of 14 weeks and 4% having additional tests at a median of 20 weeks. Univariate and multivariate analyses demonstrated that the chief determinant of the use of routine functional testing was clinical center. Aside from age (P <.0001), no baseline clinical or procedural characteristics were consistently associated with the use of routine functional testing after PTCA., Conclusions: Physicians do not appear to be adhering to the ACC/AHA guidelines for exercise testing regarding the routine use of post-PTCA functional testing. None of the clinical characteristics identified by the ACC/AHA guidelines were associated with the routine use of post-PTCA functional testing, and the primary determinant of functional testing was the location of the center at which the patient had the PTCA.