In-hospital outcomes associated with fibrinolytic and thienopyridine use in patients with ST-segment elevation acute myocardial infarction. The global registry of acute coronary events.

INTRODUCTION AND OBJECTIVES: To investigate how thienopyridine treatment, with or without associated fibrinolysis, affects the rates of major bleeding and inhospital death in patients with ST-elevation myocardial infarction (STEMI). METHODS: The rates of major bleeding and in-hospital death were studied in 14,259 consecutive patients with STEMI. During hospitalization, 5340 (38%) received thienopyridines, 3007 (21%) received fibrinolytic drugs, and 2044 (14%) received both. RESULTS: Major bleeding occurred more frequently in patients who received thienopyridines with or without fibrinolytics, in 4.6% and 4.1%, respectively, compared with 2.3% in those who received fibrinolytics alone and 2.8% in those who received neither (P< .001). Multivariate analysis, which included adjustments for risk factors for bleeding, percutaneous coronary intervention and cardiac catheterization, showed that thienopyridine treatment was an independent risk factor for bleeding (odds ratio=1.68; 95% confidence interval, 1.23-2.31). In-hospital mortality was lower in patients who received a thienopyridine, and such treatment was an independent predictor of lower mortality (odds ratio=0.50; 95% confidence interval, 0.39-0.60). CONCLUSIONS: Thienopyridine treatment was associated with an increased risk of major bleeding but also with a better in-hospital prognosis. These findings in unselected patients with STEMI, who are representative of those seen in daily clinical practice, complement, but do not replace, the data obtained in randomized clinical trails of selected patients.

Evolución hospitalaria asociada al empleo de fibrinolíticos y tienopiridinas en pacientes con infarto agudo de miocardio y elevación del segmento ST. The Global Registry of Acute Coronary Events / In-hospital outcomes associated with fibrinolytic and thienopyridine use in patients with ST-segment elevation acute myocardial infarction. The Global Registry of Acute Coronary Events

Introducción y objetivos. Investigar la incidencia de hemorragias graves y la mortalidad hospitalaria en pacientes con infarto de miocardio y elevación del segmento ST (IAMCEST) en relación con la administración de tienopiridinas con o sin tratamiento trombolítico asociado. Métodos. Se estudió la incidencia de hemorragias graves y mortalidad hospitalaria en 14.259 pacientes consecutivos con IAMCEST. En total, 5.340 (38%) pacientes recibieron tratamiento con tienopiridinas, 3.007 (21%) recibieron fármacos trombolíticos y 2.044 (14%), ambos tipos de fármacos durante el periodo de hospitalización. Resultados. Las hemorragias graves fueron más frecuentes en los pacientes que recibieron tienopiridinas con o sin fármacos trombolíticos asociados (el 4,6 y el 4,1%, respectivamente) que en los pacientes que sólo recibieron fibrinolíticos (2,3%) o ninguno de los dos tipos de fármacos (2,8%) (p < 0,001). En el análisis multivariable, ajustado para los factores de riesgo hemorrágico y cateterismo cardiaco o intervención coronaria percutánea, el tratamiento con tienopiridinas se identificó como un factor independiente de hemorragia (odds ratio [OR] = 1,68; intervalo de confianza [IC] del 95%, 1,23-2,31). La mortalidad intrahospitalaria fue menor en los pacientes que recibieron tienopiridinas, lo que se identificó como factor independiente relacionado con menor mortalidad (OR = 0,50; IC del 95%, 0,39-0,60). Conclusiones. El tratamiento con tienopiridinas se asoció con un aumento del riesgo de hemorragias, pero con mejor pronóstico intrahospitalario. Estos resultados, en pacientes no seleccionados con diagnóstico de IAMCEST y representativos de la práctica clínica diaria complementan, pero no reemplazan, la información derivada de ensayos clínicos en enfermos seleccionados y con distribución aleatoria del tratamiento (AU)

Introduction and objectives. To investigate how thienopyridine treatment, with or without associated fibrinolysis, affects the rates of major bleeding and inhospital death in patients with ST-elevation myocardial infarction (STEMI). Methods. The rates of major bleeding and in-hospital death were studied in 14 259 consecutive patients with STEMI. During hospitalization, 5340 (38%) received thienopyridines, 3007 (21%) received fibrinolytic drugs, and 2044 (14%) received both. Results. Major bleeding occurred more frequently in patients who received thienopyridines with or without fibrinolytics, in 4.6% and 4.1%, respectively, compared with 2.3% in those who received fibrinolytics alone and 2.8% in those who received neither (P < .001). Multivariate analysis, which included adjustments for risk factors for bleeding, percutaneous coronary intervention, and cardiac catheterization, showed that thienopyridine treatment was an independent risk factor for bleeding (odds ratio =1.68; 95% confidence interval, 1.23-2.31). In-hospital mortality was lower in patients who received a thienopyridine, and such treatment was an independent predictor of lower mortality (odds ratio =0.50; 95% confidence interval, 0.39-0.60). Conclusions. Thienopyridine treatment was associated with an increased risk of major bleeding but also with a better in-hospital prognosis. These findings in unselected patients with STEMI, who are representative of those seen in daily clinical practice, complement, but do not replace, the data obtained in randomized clinical trails of selected patients. risk factor for bleeding (odds ratio=1.68; 95% confidence interval, 1.23-2.31). In-hospital mortality was lower in patients who received a thienopyridine, and such treatment was an independent predictor of lower mortality (odds ratio=0.50; 95% confidence interval, 0.39-0.60). Conclusions. Thienopyridine treatment was associated with an increased risk of major bleeding but also with a better in-hospital prognosis. These findings in unselected patients with STEMI, who are representative of those seen in daily clinical practice, complement, but do not replace, the data obtained in randomized clinical trails of selected patients (AU)

Association of elevated fasting glucose with increased short-term and 6-month mortality in ST-segment elevation and non-ST-segment elevation acute coronary syndromes: the Global Registry of Acute Coronary Events.

BACKGROUND: Elevated blood glucose level at admission is associated with worse outcome after a myocardial infarction. The impact of elevated glucose level, particularly fasting glucose, is less certain in non-ST-segment elevation acute coronary syndromes. We studied the relationship between elevated fasting blood glucose levels and outcome across the spectrum of ST-segment elevation and non-ST-segment elevation acute coronary syndromes in a large multicenter population broadly representative of clinical practice. METHODS: Fasting glucose levels were available for 13 526 patients in the Global Registry of Acute Coronary Events. A multivariate logistic regression analysis was used for assessing the association between admission or fasting glucose level and in-hospital or 6-month outcome, adjusted for the variables from the registry risk scores. RESULTS: Higher fasting glucose levels were associated with a graded increase in the risk of in-hospital death (odds ratios [95% confidence intervals] vs <100 mg/dL: 1.51 [1.12-2.04] for 100-125 mg/dL, 2.20 [1.64-2.60] for 126-199 mg/dL, 5.11 [3.52-7.43] for 200-299 mg/dL, and 8.00 [4.76-13.5] for > or =300 mg/dL). When taken as a continuous variable, higher fasting glucose level was related to a higher probability of in-hospital death, without detectable threshold and irrespective of whether patients had a history of diabetes mellitus. Higher fasting glucose levels were found to be associated with a higher risk of postdischarge death up to 6 months. The risk of postdischarge death at 6 months was significantly higher with fasting glucose levels between 126 and 199 mg/dL (1.71 [1.25-2.34]) and 300 mg/dL or greater (2.93 [1.33-6.43]), but not within the 200- to 299-mg/dL range (1.08 [0.60-1.95]). CONCLUSIONS: Short-term and 6-month mortality was increased significantly with higher fasting glucose levels in patients across the spectrum of acute coronary syndromes, thus extending this relation to patients with non-ST-segment elevation myocardial infarction. The relation between fasting glucose level and risk of adverse short-term outcomes is graded across different glucose levels with no detectable threshold for diabetic or nondiabetic patients.

Association of Elevated Fasting GlucoseWith Increased Short-term and 6-Month Mortality in ST-Segment Elevation and Non–ST-Segment Elevation Acute Coronary Syndromes

Background: Elevated blood glucose level at admission is associated with worse outcome after a myocardial infarction. The impact of elevated glucose level, particularly fasting glucose, is less certain in non–ST-segment elevation acute coronary syndromes. We studied the relationshipbetween elevated fasting blood glucose levels and outcome across the spectrum of ST-segment elevation andnon–ST-segment elevation acute coronary syndromes in a large multicenter population broadly representative of clinical practice.Methods: Fasting glucose levels were available for 13 526 patients in the Global Registry of Acute Coronary Events. A multivariate logistic regression analysis was used forassessing the association between admission or fasting glucose level and in-hospital or 6-month outcome, adjustedfor the variables from the registry risk scores. Results: Higher fasting glucose levels were associated with a graded increase in the risk of in-hospital death (odds ratios [95% confidence intervals] vs 100 mg/dL: 1.51 [1.12-2.04] for 100-125 mg/dL, 2.20 [1.64-2.60] for 126-199 mg/ dL, 5.11 [3.52-7.43] for 200-299 mg/dL, and 8.00 [4.76-13.5] for 300 mg/dL). When taken as a continuous variable, higher fasting glucose level was related to a higherprobability of in-hospital death, without detectable threshold and irrespective of whether patients had a history ofdiabetes mellitus. Higher fasting glucose levels were found to be associated with a higher risk of postdischarge deathup to 6 months. The risk of postdischarge death at 6 monthswas significantly higher with fasting glucose levels between 126 and 199 mg/dL (1.71 [1.25-2.34]) and 300mg/dL or greater (2.93 [1.33-6.43]), but not within the 200- to 299-mg/dL range (1.08 [0.60-1.95])...

Bleeding events with antithrombotic therapy in patients with unstable angina or non-ST-segment elevation myocardial infarction; insights from a large clinical practice registry (GRACE).

BACKGROUND: Thienopyridine use, in particular clopidogrel in acute coronary syndromes, has been associated with an improvement in outcome. However, little information is available regarding their bleeding risk when used in combination with other antithrombotic agents and revascularisation. METHODS: In a large, multinational, prospective registry, the Global Registry of Acute Coronary Events, the major bleeding rate (using GRACE criteria) of 27,358 patients with unstable angina or non-ST-elevation myocardial infarction was recorded during index admission. The interaction of thienopyridines on major bleeding with other antithrombotic agents and with revascularisation was analysed. RESULTS: The 11,478 patients who received thienopyridines during hospitalisation experienced a significant increase in major bleeding (2.8% with thienopyridines, 2.2% without thienopyridines; p=0.002). No significant interaction with glycoprotein IIb/IIIa inhibitors and thienopyridines was seen with regard to bleeding. Thienopyridines with unfractionated heparin did not alter bleeding risk, but thienopyridines with low molecular weight heparin was associated with a significant excess of bleeding (2.1% with thienopyridines, 1.3% without thienopyridines; p=0.004). There was no significant difference in major bleeding with thienopyridines in patients who did or did not undergo revascularisation. CONCLUSIONS: Major bleeding was increased in patients receiving thienopyridines. No increase in bleeding risk was seen in patients having revascularisation.

Interactions between heparins, glycoprotein IIb/IIIa antagonists, and coronary intervention. The Global Registry of Acute Coronary Events (GRACE).

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.

Use of proven therapies in non-ST-elevation acute coronary syndromes according to evidence-based risk stratification.

BACKGROUND: Current guidelines advise the use of risk stratification to determine which patients should receive more aggressive antithrombotic and invasive therapies. Our objective was to evaluate the relationship between risk stratification and therapeutic decision making in patients with non-ST-segment elevation acute coronary syndromes. METHODS: We analyzed data from 15,026 patients with acute coronary syndrome who were enrolled into the GRACE registry between 1999 and 2003. We assessed the evidence-based use of antithrombotic therapy and early invasive strategy according to risk profile defined by baseline troponin elevation, presenting ST-segment depression, and GRACE risk score. Patients with possible contraindications were removed to define the use of therapies specifically among clearly eligible patients. RESULTS: Patients with elevated troponin were more likely to receive enoxaparin (60% vs 50.4%, respectively), GP IIb/IIIa inhibitors (32.8% vs 17.6%), and to undergo catheterization (66% vs 54%) and percutaneous coronary intervention (37.4% vs 25.6%; all P < .0001). Patients with ST depression received modestly more enoxaparin and GP IIb/IIIa than those without ST depression, but not more catheterization (P = .8) or percutaneous coronary intervention (P = .09). Highest risk patients were somewhat less likely to receive enoxaparin (P < .0001) and cardiac catheterization (P = .0002) according to GRACE risk deciles. CONCLUSIONS: In spite of current guidelines recommending the use of selected therapies in high-risk patients, there is no clear correlation of use of effective therapies with overall risk profile even among eligible patients. Thus, there is substantial opportunity to improve use of effective therapies, especially in high-risk populations.

Invasive vs non-invasive treatment in acute coronary syndromes and prior bypass surgery.

BACKGROUND: We evaluated the association between invasive and non-invasive management and hospital and 6-month outcomes in patients with a prior coronary artery bypass graft (CABG) who experienced an acute coronary syndrome. METHODS: Data were analysed from patients with a prior CABG who developed an acute coronary syndrome and were enrolled in the Global Registry of Acute Coronary Events. From 44,991 patients included in the study, 3853 fulfilled the inclusion criteria. Of these, 3356 received non-invasive treatment approaches while 497 underwent invasive treatment (percutaneous coronary intervention [PCI] within 48 h of admission). RESULTS: The primary composite endpoint of death, non-fatal myocardial infarction, and recurrent ischaemia during hospitalization was similar in patients in the non-invasive and invasive groups (31% vs 30%, respectively; P=0.53). The rates of hospital mortality (non-invasive 3.4% vs invasive 3.2%) and non-fatal myocardial infarction (3.4% vs 5.1%, respectively) were similar. At 6-month follow-up, the mortality rate was 6.5% in the non-invasive group vs 3.4% in the invasive group (P<0.02); the combined endpoint of death or myocardial infarction was lower in the invasive group (P<0.01). Multivariable analysis showed that, at 6-month follow-up, the combined endpoint of death, non-fatal myocardial infarction, and rehospitalization for heart disease was similar (P=0.10). A greater proportion of patients in the invasive group required unscheduled diagnostic and therapeutic invasive procedures compared with those in the non-invasive group (angiography 15.4% vs 8.1%; PCI 10% vs 5.0%; both P<0.001). CONCLUSIONS: The results from this observational study show no statistically significant differences in hospital outcomes between acute coronary syndrome patients with a prior CABG who undergo invasive or non-invasive treatment. Invasively treated patients experienced higher rates of readmission and additional cardiac procedures than non-invasively treated patients but a lower incidence of cardiovascular complications at 6 months.

Patterns of use and potential impact of early beta-blocker therapy in non-ST-elevation myocardial infarction with and without heart failure: the Global Registry of Acute Coronary Events.

BACKGROUND: Early beta-blocker (BB) therapy improves outcomes in ST-segment elevation myocardial infarction; however, limited data are available on its early use and its impact in non-ST-segment elevation myocardial infarction (NSTEMI). METHODS: We evaluated data from 7106 patients with NSTEMI, without contraindications to BBs, enrolled in the Global Registry of Acute Coronary Events between April 1999 and September 2004. Baseline characteristics, management, and outcomes were analyzed according to the use of oral (+/-intravenous) BB within 24 hours of presentation. Multivariable analysis was conducted adjusting for comorbidities using the Global Registry of Acute Coronary Events risk model (c statistic 0.83). RESULTS: Beta-blocker therapy was initiated within the first 24 hours in 76% of patients with NSTEMI (79% with Killip class I vs 62% with class II/III; P < .001). Failure to initiate BBs within the first 24 hours was associated with lower rates of subsequent BB therapy (P < .001) and other evidence-based therapies. Early BB therapy was correlated with lower hospital mortality for NSTEMI patients (OR 0.58, 95% CI 0.42-0.81) and for those with Killip class II/III (OR 0.39, 95% CI 0.23-0.68) with a trend toward lower mortality in the Killip class I group (OR 0.77, 95% CI 0.49-1.21). At 6 months postdischarge, early BB use was associated with lower mortality in NSTEMI patients (OR 0.75, 95% CI 0.56-0.997) with a trend toward lower mortality in patients with Killip class I or II/III. CONCLUSIONS: Many eligible patients do not receive early BB therapy. Treatment with early BBs may have a beneficial impact on hospital and 6-month mortality in all patients, including those presenting with heart failure.

Prediction of risk of death and myocardial infarction in the six months after presentation with acute coronary syndrome: prospective multinational observational study (GRACE).

OBJECTIVE: To develop a clinical risk prediction tool for estimating the cumulative six month risk of death and death or myocardial infarction to facilitate triage and management of patients with acute coronary syndrome. DESIGN: Prospective multinational observational study in which we used multivariable regression to develop a final predictive model, with prospective and external validation. SETTING: Ninety four hospitals in 14 countries in Europe, North and South America, Australia, and New Zealand. POPULATION: 43,810 patients (21,688 in derivation set; 22,122 in validation set) presenting with acute coronary syndrome with or without ST segment elevation enrolled in the global registry of acute coronary events (GRACE) study between April 1999 and September 2005. MAIN OUTCOME MEASURES: Death and myocardial infarction. RESULTS: 1989 patients died in hospital, 1466 died between discharge and six month follow-up, and 2793 sustained a new non-fatal myocardial infarction. Nine factors independently predicted death and the combined end point of death or myocardial infarction in the period from admission to six months after discharge: age, development (or history) of heart failure, peripheral vascular disease, systolic blood pressure, Killip class, initial serum creatinine concentration, elevated initial cardiac markers, cardiac arrest on admission, and ST segment deviation. The simplified model was robust, with prospectively validated C-statistics of 0.81 for predicting death and 0.73 for death or myocardial infarction from admission to six months after discharge. The external applicability of the model was validated in the dataset from GUSTO IIb (global use of strategies to open occluded coronary arteries). CONCLUSIONS: This risk prediction tool uses readily identifiable variables to provide robust prediction of the cumulative six month risk of death or myocardial infarction. It is a rapid and widely applicable method for assessing cardiovascular risk to complement clinical assessment and can guide patient triage and management across the spectrum of patients with acute coronary syndrome.

Image-guided resection of high-grade glioma: patient selection factors and outcome.

OBJECT: In patients with glioma, image-guided surgery helps to define the radiographic limits of the tumor to maximize safety and the extent of resection while minimizing damage to eloquent brain tissue. The authors hypothesize that image-guided resection (IGR) techniques are associated with improved outcomes in patients with malignant glioma. METHODS: Data recorded in 486 patients enrolled in the Glioma Outcomes Project were analyzed in this study. Demographic data and outcomes in patients who underwent IGR were compared with those in patients who underwent resection without IGR. Univariate analysis performed with chi-square testing was used to compare patient presentation, tumor characteristics, and death rates. Multivariate logistic regression was used to predict various outcome parameters. Patients who underwent IGR were younger and had smaller, lower-grade tumors than those in whom IGR was not performed. They were more likely to present with seizure and normal consciousness. Unexpectedly, gross-total resection was performed in significantly fewer patients with IGR than in individuals without IGR. Patients with IGR were more likely to be discharged home with the ability to live independently, and they had a shorter duration of hospital stay than patients without IGR. Survival was significantly longer in patients who underwent IGR, but multivariate analysis showed that glioblastoma multiforme (GBM) and age accounted for these observations. CONCLUSIONS: Selection bias occurs regarding patients who receive IGR; these biases include younger age, presentation with seizure and normal level of consciousness, tumor diameter less than 4 cm, and non-GBM on histopathological studies. Outcome appears to be improved in patients who undergo IGRs of high-grade gliomas. It is unclear if these improved outcomes are due to the selection of a more favorable patient population or to the IGR techniques themselves. It is likely that the full potential of image guidance in glioma surgery will not be realized until it is applied to a wider range of patients.

Circulating secretory phospholipase A2 activity predicts recurrent events in patients with severe acute coronary syndromes.

OBJECTIVES: The purpose of this study was to determine the prognostic value of circulating secretory phospholipase A2 (sPLA2) activity in patients with acute coronary syndromes (ACS). BACKGROUND: The plasma level of type IIA sPLA2 is a risk factor for coronary artery disease (CAD) and is associated with adverse outcomes in patients with stable CAD. The prognostic impact of sPLA2 in patients with ACS is unknown. METHODS: Secretory phospholipase A2 antigen levels and activity were measured in plasma samples of 446 patients with ACS, obtained at the time of enrollment. RESULTS: Baseline sPLA2 activity was associated with the risk of death and myocardial infarction (MI). The unadjusted rate of death and MI increased in a stepwise fashion with increasing tertiles of sPLA2 activity (p < 0.0001). The association remained significant in the subgroup of patients who had MI with ST-segment elevation (p = 0.014) and the subgroup of patients who had unstable angina or non-ST-segment elevation MI (p < 0.002). After adjustment for clinical and biological variables, the hazard ratios for the combined end point of death or MI in the third tertile of sPLA2 compared with the first and second tertiles was 3.08 (95% confidence interval, 1.37 to 6.91, p = 0.006). CONCLUSIONS: A single measurement of plasma sPLA2 activity at the time of enrollment provides strong independent information to predict recurrent events in patients with ACS.

In-hospital revascularization and one-year outcome of acute coronary syndrome patients stratified by the GRACE risk score.

In the prospective, multicenter Canadian Acute Coronary Syndromes Registry, in-hospital revascularization was independently associated with better 1-year survival only among patients with high-risk non-ST-elevation acute coronary syndromes stratified by the Global Registry of Acute Coronary Events risk score; similar benefits were not observed in the low- and intermediate-risk groups. The Global Registry of Acute Coronary Events risk score appears to be a useful risk stratification tool that identifies high-risk patients for whom more aggressive treatment is warranted.

Treating patients with acute coronary syndromes with aggressive antiplatelet therapy (from the Global Registry of Acute Coronary Events).

Few data exist on the use of aggressive combination therapy with thienopyridines and glycoprotein IIb/IIIa inhibitors in higher risk patients with an acute coronary syndrome (ACS). The aim of this study was to characterize the combined use of these agents and the associated hospital outcomes in patients with ACS enrolled in the multinational Global Registry of Acute Coronary Events. Data from 8,081 patients with non-ST-segment elevation myocardial infarction or unstable angina were analyzed. Of these patients, 5,070 (62.7%) received aspirin and a thienopyridine, and the remainder received aspirin, a thienopyridine, and a glycoprotein IIb/IIIa blocker. The presence of a non-ST-segment elevation myocardial infarction; a history of diabetes or coronary artery bypass surgery; performance of in-hospital catheterization, percutaneous coronary intervention, or coronary artery bypass grafting; and in-hospital use of heparin were independent predictors of the use of triple antiplatelet therapy with aspirin, thienopyridines, and glycoprotein IIb/IIIa blockers. Increased diastolic blood pressure and increased serum creatinine were associated with a failure to prescribe triple therapy. An increased risk of major bleeding during hospitalization was associated with the use of triple antiplatelet therapy (odds ratio 1.6, 95% confidence interval 1.2 to 2.2). Aggressive antiplatelet therapy was used in approximately 2 of every 5 patients presenting with an ACS. Triple therapy was associated with the performance of catheterization and/or percutaneous coronary intervention, as well as high-risk patient features. Although no differences in hospital death rates were evident in patients receiving triple therapy, this population was at significantly increased risk of major bleeding episodes during hospitalization.

Medication performance measures and mortality following acute coronary syndromes.

PURPOSE: To identify patient and health care factors which are related to the use of medical treatments that comprise quality measures and to assess the relation of these measures with mortality. METHODS: The study sample consisted of 20 140 patients with acute coronary syndromes from the international GRACE registry. Multivariable logistic regression modeling was used to determine predictors of quality performance. Quality indicators were use of aspirin and beta-blockers within 24 hours and at hospital discharge, use of angiotensin-converting enzyme (ACE) inhibitors at discharge, and in-hospital mortality. RESULTS: Use of medications in eligible patients at discharge ranged from 73% for ACE inhibitors to 93% for aspirin. High-risk features (eg, heart failure, older age) were related to failure to use aspirin and beta-blockers. Being at a teaching hospital and care by a cardiologist were associated with better use of aspirin and beta-blockers. Coronary artery bypass surgery was associated with failure to use ACE inhibitors and aspirin. When hospitals were divided into quartiles of quality performance, adjusted in-hospital mortality was 4.1% in the top versus 5.6% in the bottom quartile, representing a 27% (95% confidence interval: 11% to 42%) lower relative mortality. CONCLUSION: Identification of factors associated with failure to use proven treatments, including high-risk groups that would derive particular benefit from effective therapies, provides an opportunity to focus quality improvement interventions. The association of lower hospital mortality with better use of selected medical treatments supports their measurement to improve quality of care.

Relation of timing of cardiac catheterization to outcomes in patients with non-ST-segment elevation myocardial infarction or unstable angina pectoris enrolled in the multinational global registry of acute coronary events.

We assessed whether timing of catheterization is associated with the type of non-ST-segment elevation acute coronary syndrome and/or outcome in patients who were enrolled in the Global Registry of Acute Coronary Events. Overall, 8,853 patients who had unstable angina pectoris or non-ST-elevation myocardial infarction were categorized according to timing of catheterization: expeditive (<24 hours), early (24 to 48 hours), and delayed (>48 hours). Patients in the delayed group were older, more frequently had previous myocardial infarction or stroke, and had a higher risk score compared with those in the expeditive and early groups (all p < or =0.001). Killip class IV at admission, non-ST-elevation myocardial infarction, and Q waves after the index electrocardiogram were more common in the expeditive group (all p <0.0001). Patients in the expeditive and early groups were treated more aggressively with medications than were those in the delayed group. The in-hospital composite end point (death, stroke, or major bleed) occurred most frequently in the expeditive group (expeditive 6.6%, early 3.9%, delayed 5.1%, p = 0.0005), as did in-hospital death (expeditive 3.5%, early 1.4%, delayed 2.0%, p <0.0001). The highest incidence of death during follow-up occurred in the delayed group (3.8% delayed vs 2.8% expeditive/early, p = 0.0210). Multivariate regression analysis suggested that expeditive catheterization was related to in-hospital death and death from time of catheterization to 6 months. We conclude that expeditive catheterization is associated with unstable presenting features that contribute significantly to the higher risk of death and death or myocardial infarction in hospital compared with patients who undergo later catheterization.

Magnitude of and risk factors for in-hospital and postdischarge stroke in patients with acute coronary syndromes: findings from a Global Registry of Acute Coronary Events.

BACKGROUND: Stroke is a recognized complication after acute myocardial infarction, but few studies have investigated the incidence and outcome of stroke in patients with acute coronary syndrome (ACS). This study examined the incidence and outcomes of hemorrhagic and nonhemorrhagic stroke and risk factors associated with stroke in patients with ACS. METHODS AND RESULTS: Data were obtained from 35,233 patients enrolled in the Global Registry of Acute Coronary Events (GRACE) with an ACS. In-hospital strokes occurred in 310 patients (0.9%), of which 100 (32.6%) were fatal. The incidence of in-hospital stroke was significantly higher in patients with ST-segment-elevation myocardial infarction than in non-ST-segment myocardial infarction or unstable angina (1.3%, 0.9%, 0.5%, respectively; P<0.001). Overall, 35.5% of in-hospital strokes occurred within 6 days of hospitalization. The strongest risk factor for in-hospital nonhemorrhagic stroke was in-hospital CABG, followed by in-hospital atrial fibrillation, previous stroke, initial enzyme elevation, and advanced age. Prior statin use was a protective factor. After controlling for potential confounders, in-hospital mortality was significantly higher among patients who experienced an in-hospital stroke (adjusted odds ratio, 8.3; 95% CI, 6.0 to 11.4). A total of 269 additional strokes (1.1%) occurred within 6 months after discharge from hospital, of which 56 (20.9%) were fatal. The most important risk factor for postdischarge stroke was the occurrence of an in-hospital stroke. CONCLUSIONS: Stroke is an uncommon event in patients with ACS but is associated with high mortality. Despite current therapy, the incidence of postdischarge stroke is not low. New approaches are warranted to reduce the risk of stroke in patients with ACS.

Impact of combined pharmacologic treatment with clopidogrel and a statin on outcomes of patients with non-ST-segment elevation acute coronary syndromes: perspectives from a large multinational registry.

AIMS: To evaluate clinical outcomes associated with the combined use of clopidogrel and statins vs. clopidogrel alone on a background of aspirin therapy in patients with the spectrum of acute coronary syndromes (ACS). METHODS AND RESULTS: Utilizing data from the Global Registry of Acute Coronary Events, we studied 15 693 patients admitted with non-ST-segment elevation myocardial infarction (MI) or unstable angina, dividing them according to discharge medications: aspirin alone (group I); aspirin + clopidogrel (group II); aspirin + statin (group III); aspirin + clopidogrel + statin (group IV). Among the groups of patients in whom clopidogrel was used (groups II and IV), group II patients were older, more likely to have prior MI, but less likely to have a history of prior revascularization. In-hospital cardiac catheterization and revascularization rates were similar between groups II and IV. Importantly, Kaplan-Meier analysis showed that the 6 month mortality rate was lower in group IV (log-rank test 22.8, P<0.0001). The hazard ratio for the 6 month mortality rate was adjusted using the Cox proportional hazard model for confounding variables and for propensity score, and the 6 month mortality rate for patients in group IV remained lower compared with those in group II [0.59 (0.41-0.86), P<0.0001]. CONCLUSION: Our data suggest that the combination of clopidogrel with a statin has synergistic effects on the clinical outcomes of patients with non-ST-segment elevation ACS.

A validated prediction model for all forms of acute coronary syndrome: estimating the risk of 6-month postdischarge death in an international registry.

CONTEXT: Accurate estimation of risk for untoward outcomes after patients have been hospitalized for an acute coronary syndrome (ACS) may help clinicians guide the type and intensity of therapy. OBJECTIVE: To develop a simple decision tool for bedside risk estimation of 6-month mortality in patients surviving admission for an ACS. DESIGN, SETTING, AND PATIENTS: A multinational registry, involving 94 hospitals in 14 countries, that used data from the Global Registry of Acute Coronary Events (GRACE) to develop and validate a multivariable stepwise regression model for death during 6 months postdischarge. From 17,142 patients presenting with an ACS from April 1, 1999, to March 31, 2002, and discharged alive, 15,007 (87.5%) had complete 6-month follow-up and represented the development cohort for a model that was subsequently tested on a validation cohort of 7638 patients admitted from April 1, 2002, to December 31, 2003. MAIN OUTCOME MEASURE: All-cause mortality during 6 months postdischarge after admission for an ACS. RESULTS: The 6-month mortality rates were similar in the development (n = 717; 4.8%) and validation cohorts (n = 331; 4.7%). The risk-prediction tool for all forms of ACS identified 9 variables predictive of 6-month mortality: older age, history of myocardial infarction, history of heart failure, increased pulse rate at presentation, lower systolic blood pressure at presentation, elevated initial serum creatinine level, elevated initial serum cardiac biomarker levels, ST-segment depression on presenting electrocardiogram, and not having a percutaneous coronary intervention performed in hospital. The c statistics for the development and validation cohorts were 0.81 and 0.75, respectively. CONCLUSIONS: The GRACE 6-month postdischarge prediction model is a simple, robust tool for predicting mortality in patients with ACS. Clinicians may find it simple to use and applicable to clinical practice.

Determinants and prognostic impact of heart failure complicating acute coronary syndromes: observations from the Global Registry of Acute Coronary Events (GRACE).

BACKGROUND: Few data are available on the impact of heart failure (HF) across all types of acute coronary syndromes (ACS). METHODS AND RESULTS: The Global Registry of Acute Coronary Events (GRACE) is a prospective study of patients hospitalized with ACS. Data from 16 166 patients were analyzed: 13 707 patients without prior HF or cardiogenic shock at presentation were identified. Of these, 1778 (13%) had an admission diagnosis of HF (Killip class II or III). HF on admission was associated with a marked increase in mortality rates during hospitalization (12.0% versus 2.9% [with versus without HF], P<0.0001) and at 6 months after discharge (8.5% versus 2.8%, P<0.0001). Of note, HF increased mortality rates in patients with unstable angina (defined as ACS with normal biochemical markers of necrosis; mortality rates: 6.7% with versus 1.6% without HF at admission, P<0.0001). By logistic regression analysis, admission HF was an independent predictor of hospital death (odds ratio, 2.2; P<0.0001). Admission HF was associated with longer hospital stay and higher readmission rates. Patients with HF had lower rates of catheterization and percutaneous cardiac intervention, and fewer received beta-blockers and statins. Hospital development of HF (versus HF on presentation) was associated with an even higher in-hospital mortality rate (17.8% versus 12.0%, P<0.0001). In patients with HF, in-hospital revascularization was associated with lower 6-month death rates (14.0% versus 23.7%, P<0.0001; adjusted hazard ratio, 0.5; 95% CI, 0.37 to 0.68, P<0.0001). CONCLUSIONS: In this observational registry, heart failure was associated with reduced hospital and 6-month survival across all ACS subsets, including patients with normal markers of necrosis. More aggressive treatment of these patients may be warranted to improve prognosis.