Presentation on theme: "Global Registry of Acute Coronary Events Assessing Today’s Practice Patterns to Enhance Tomorrow’s Care Acute coronary syndromes (ACS) represent a broad."— Presentation transcript:
1 Global Registry of Acute Coronary Events Assessing Today’s Practice Patterns to Enhance Tomorrow’s CareAcute coronary syndromes (ACS) represent a broad spectrum of conditions from the standpoint of diagnosis, treatment and prognosis. They range from unstable angina (UA) to non-ST-segment elevation myocardial infarction (NSTEMI) and ST-segment elevation myocardial infarction (STEMI).Use of fibrinolytic agents for patients with STEMI, combined with the use of other medical therapies such as low-molecular-weight heparin, unfractionated heparin, aspirin, and platelet inhibitors, have been shown to improve the outcomes for patients with ACS. However, no systematic studies have been carried out to characterize the prevalence of ACS, or to evaluate the clinical characteristics of patients with ACS or their routine daily management, especially from a worldwide perspective.In 1997, in response to the gap in understanding of ACS, discussions began about setting up a study into the management and outcomes of ACS patients. By early 1999, a pilot study was under way, which tested the feasibility of the project, and evaluated the data-collection methods and the case-report form. By mid-1999 the study, known as GRACE, or the Global Registry of Acute Coronary Events, was launched.Supported by an unrestricted educational grant from sanofi-aventis to the Center for Outcomes Research University of Massachusetts Medical School
2 What is GRACE? Global Registry of Acute Coronary Events Largest multinational registry covering the full spectrum of ACSGeneralizable patient inclusion criteriaIn-hospital and 6-month follow-upRepresentative of the catchment population: (clusters of hospitals)Full spectrum of hospitals and facilitiesTraining, audit and quality control
3 International Scientific Advisory Committee International Advisory Committee‘Americas’ clustersChair: JM Gore‘European’ clustersChair: KAA Fox8 advisors8 advisorsThe International Advisory Committee for GRACE comprises the principal investigator from each of the 16 clusters. Two Co-Chairs have been elected, one of whom oversees clusters in the ‘Americas’ and the other the non-American clusters. There are nine advisors and 40 subsite cardiologists for the ‘European’ clusters, and eight advisors and 41 subsite cardiologists for the ‘Americas’ clusters.40 subsite cardiologists40 subsite cardiologists
4 Scientific Advisory Committee Co-Chairs Keith AA Fox, UKJoel M Gore, USAPublications Kim A Eagle, USACo-Chairs Ph Gabriel Steg, FranceStudy Co-ordination Fred Anderson, University of MassachusettsArgentinaEnrique GurfinkelAustralia/New ZealandDavid BriegerAustriaGeorg GaulBelgiumFrans J Van de WerfBrazilÁlvaro AvezumCanadaShaun GoodmanGermanyDietrich C GulbaItalyGiancarlo AgnelliFranceGilles MontalescotPh Gabriel StegPolandAndrzej BudajSpainJosé López-SendónUnited KingdomKeith AA FoxMarcus FlatherUnited StatesFrederick A AndersonKim A EagleRobert J GoldbergJoel M GoreChristopher B GrangerBrian M Kennelly
5 Objectives of GRACEIdentify opportunities to improve the quality of care for patients with ACSDescribe diagnostic & treatment strategies, & hospital & post-discharge outcomesDevelop hypotheses for future clinical researchDisseminate findings to a wider audienceThe goal of GRACE is to improve the medical treatment of patients with ACS through better understanding of patient demographics, management, and in-hospital and post-discharge outcomes.The objectives of GRACE are to:Provide detailed data to the medical community to characterize current and evolving practice patterns, delivery of care, and resource utilization in the management of ACS.Provide data to support internal and external standards and benchmarking of treatment patterns and patient outcomes.Analyze the data collected in the GRACE database and design ancillary studies to address unanswered clinical questions.Disseminate findings through the publication of manuscripts in peer-reviewed medical journals.
6 Core GRACE Study Design ~100 hospitals in 14 countriesEurope, North & South America, Australia, New ZealandPopulation-based clusters with community hospitals and referral centresFirst consecutive cases per centre/month: qualifying symptoms PLUS evidence of CADRandom audit of all centres: 3 year cycle
7 Cluster Strategy for Study Sites: Population-Based Design 21318 advisorycommitteemembers~100 hospitals~10,000 ACSpatients/yearCurrently, 84 hospitals organized into 17 geographic clusters, each of which is led by a member of the International Advisory Committee, are participating in GRACE. These 17 regions were chosen to reflect the type of care received by patients with ACS in populations that vary according to demographic, clinical and treatment characteristics.1The design of GRACE is such that an unbiased and generalizable sample of patients with ACS is enrolled within each of the 17 locations. For each hospital, the first 10–20 qualifying cases (depending on the hospital size) discharged each month are enrolled in the registry. This approach results in approximately 120 cases per hospital being enrolled each year.1. The GRACE Investigators. Rationale and design of the GRACE (Global Registry of Acute Coronary Events) Project: a multinational registry of patients hospitalized with acute coronary syndromes. Am Heart J 2001;141:190–9.645
8 Multinational Site Network Argentina 6 sitesAustralia 7 sitesAustria siteBelgium 6 sitesBrazil 7 sitesCanada 6 sitesFrance 6 sitesGermany 5 sitesItaly 5 sitesNew Zealand 2 sitesPoland 6 sitesSpain 4 sitesUK 5 sitesUSA 18 sitesCurrently, 84 hospitals organized into 17 geographic clusters in 14 countries are participating in GRACE. These 17 regions were chosen to represent the type of care received by ACS patients in populations that varied according to patient demographics, and clinical and treatment characteristics.
9 89 Active Core Study Sites: 17 Clusters in 14 Countries Eighty-four study sites in 14 countries spanning four continents – North and South America, Europe, and Australia and New Zealand – are involved in recruiting patients for GRACE. Data collection began in April 1999, with the aim of enrolling 10,000 patients with ACS each year.
10 Status of 17 Core Clusters 70,359 cases enrolled85% six-month follow-upAs of June 2007, 84 hospitals located in 14 countries across four continents are involved in enrolling patients in GRACE. A total of 66,456 case-report forms have been received, and the post-discharge follow-up rate is 85%. One hundred five abstracts have been presented or have been accepted for presentation at major cardiology meetings, and sixty-three manuscripts have been published in peer-reviewed journals or are in press.Q4-2007
11 The “Big Picture” Core GRACE & GRACE2 GRACE CoreSubstudy 1Substudy 2Substudy 3The ongoing GRACE expansion, or GRACE2, has been launched to enable hospitals in countries that are not involved in the core GRACE study to participate in the project. As of August 2001, 158 hospitals in 23 countries – Australia, Austria, Bangladesh, Brazil, Bulgaria, Canada, China, Colombia, Ecuador, El Salvador, Guatemala, Italy, Latvia, Panama, Peru, Poland, Portugal, Romania, Ukraine, United Arab Emirates, United States, Uruguay, Venezuela – are actively enrolling patients in GRACE2. An additional 100 sites are expected to join the study.All publications arising from the GRACE database and any substudies will remain under the auspices of the core GRACE investigators.GRACE Core70,359 patients89 hospitals14 countriesGRACE231,982 patients158 hospitals23 countries
12 247 Core GRACE & GRACE2 Study Sites in 30 Countries* Eighty-four study sites in 14 countries spanning four continents – North and South America, Europe, and Australia and New Zealand – are involved in recruiting patients for GRACE. Data collection began in April 1999, with the aim of enrolling 10,000 patients with ACS each year.*30 countries = 16 GRACE2 + 7 core GRACE + 7 both
13 Status: December 31, 2007 89 Core & 158 Expanded Sites 30 countries247 hospitals102,341 casesAs of June 2007, 84 hospitals located in 14 countries across four continents are involved in enrolling patients in GRACE. A total of 66,456 case-report forms have been received, and the post-discharge follow-up rate is 85%. One hundred five abstracts have been presented or have been accepted for presentation at major cardiology meetings, and sixty-three manuscripts have been published in peer-reviewed journals or are in press.Q4-2007
15 Hospital Characteristics Q4-2001 vs. Current Quarter Q Q4-2007Number of HospitalsCoronary care unit 94% %Emergency department 86% %Cardiac catheterization laboratory % %Open heart surgery % %Hospital beds (mean)Coronary care unit beds (mean)ACS admissions (mean, per year)The majority of hospitals involved in GRACE have a coronary care unit and an emergency department. Over two-thirds of hospitals have access to cardiac catheterization facilities and one-half perform open heart surgery. The mean number of hospital beds is over 500, and the mean number of beds in the coronary care unit is 11. Each year, an average of over 600 patients are admitted to each hospital for suspected ACS.Q4-2007
16 70,359 Cases Enrolled as of December 31, 2007 Q4-2007
17 Classification of Cases The most common diagnosis for patients with ACS enrolled in the GRACE study is STEMI, with around one-third of patients hospitalized with the condition. The second most common category of ACS is NSTEMI at 30%, followed by UA at 29%. A minority of patients were diagnosed with ‘other cardiac’ or ‘noncardiac’ diagnoses.Q4-2007
18 Hospital Discharge Status STEMI NSTEMI UADeath 7% 4% 3%Home 77% 78% 87%Transfer * 10% 12% 9%Other 6% 6% 2%*Transfer to another acute care hospital.Q4-2007
19 Admission versus Final Diagnosis UAN=4999(44%)‘Rule-out’ MIN=957(9%)Unspecified chest painN=745(7%)Other cardiacN=381(3%)Non-cardiacN=125(1%)STEMIN=3419(30%)Non-STEMIN=2893(25%)Unstable anginaN=4397(38%)N=508(4%)N=326MIN=4100(36%)*Missing diagnosis in 236 patientsAdmission diagnoses versus final diagnoses (derived from discharge diagnosis, electrocardiographic changes and cardiac enzymes) in 11,543 patients with acute coronary syndromes. Figures expressed as percentage of total ACS.Fox KAA et al.Eur Heart J 2002;23:
20 Baseline Characteristics STEMI NSTEMI UA (n = 13,862) (11,316) (12,509)Median age (years)Male (%)Prior history (%)AnginaMyocardial infarctionPCI/CABG 8/5 15/14 25/19SmokingDiabetes mellitusHypertensionHyperlipidemiaParticipant in clin trial (%)
21 Hospital Treatment According to Admission Diagnosis MI UA ? MI Chest painn , , , ,266% % % %ACE inhibitorsAspirin-blockersCa2+ blockersGp IIb/IIIa: no PCIGp IIb/IIIa with PCILMWHUFHThrombolytic agents
26 Hospital Outcomes <0.0001 10.7 <0.0001 5.6 5.6 4.0 Lankes W et al.Eur Heart J 2002;23(Abstr Suppl):502.
27 What proportion of eligible patients receive reperfusion therapy?
28 Practice variation and missed opportunities for reperfusion in ST-segment-elevation myocardial infarction: findings from the Global Registry of Acute Coronary Events (GRACE)Kim A. Eagle, Shaun G. Goodman, Álvaro Avezum, Andrzej Budaj, Cynthia M. Sullivan, José López-Sendón, for the GRACE InvestigatorsLancet 2002;359:373-77
29 Missed Opportunities for Reperfusion ST ↑ or LBBB, <12 hrs from onset, no contraindicationsANC (%) US (%) AB (%) EUR (%)nPCI aloneLytic aloneBothNeitherAB, Argentina/Brazil; ANC, Australia/New Zealand/Canada; EUR, Europe; US, United StatesEagle KA et al. Lancet 2002;359:373-7.
30 Independent Predictors of No Reperfusion Variable OR (95% CI)Prior CABG ( )History of diabetes ( )History of congestive heart failure ( )Presentation without chest pain ( )*Age 75 years ( )*As compared to the <55 years age groupEagle KA et al. Lancet 2002;359:373-7.
31 Geographical Variation: Admission to Hospitals with/without Access to Cath Lab ANC, Australia/New Zealand/Canada; AB, Argentina/Brazil
32 Global patterns of use of antithrombotic and antiplatelet therapies in patients with acute coronary syndromes: Insights from the Global Registry of Acute Coronary Events (GRACE)Andrzej Budaj, David Brieger, Ph Gabriel Steg, Shaun G. Goodman, Omar H. Dabbous, Keith A. A. Fox, Álvaro Avezum, Christopher P. Cannon, Tomasz Mazurek, Marcus D. Flather, and Frans Van De Werf, for the GRACE InvestigatorsAm Heart J 2003;146:
33 Geographic Practice Variation Budaj A et al. Am Heart J 2003;146:
34 Antithrombotic Rx Used Cannon CP et al.Eur Heart J 2001;22(Abstr Suppl):592.
35 Incidence of Major Bleeding Cannon CP et al.Eur Heart J 2001;22(Abstr Suppl):592.
36 Multivariate Adjusted Odds of Major Hemorrhage 3.9%2.4%8.3%2.9%UFHLMWHUFH + IIb/IIIaLMWH +IIb/IIIaOR=0.55P<0.001OR=2.26The baseline characteristics of the population were well matched between the three treatment groups. Mean age was 60, 25% were female, 56% of patients had an MI at presentation and 9% presented with signs of congestive heart failure defined by Killip class. One quarter had the onset of ACS within 24 hoursLowerHigherCannon CP et al.Eur Heart J 2001;22(Abstr Suppl):592.4
37 Safety EventsCannon CP et al.Eur Heart J 2001;22(Abstr Suppl):592.
38 Major Cardiac EventsCannon CP et al.Eur Heart J 2001;22(Abstr Suppl):592.
39 Predictors of major bleeding in acute coronary syndromes: the Global Registry of Acute Coronary Events (GRACE)M. Moscucci, K.A.A. Fox, Christopher P. Cannon, W. Klein, José López-Sendón, G. Montalescot, K. White, R.J. Goldberg, for the GRACE InvestigatorsEuropean Heart Journal 2003;24:
40 Incidence of Major Bleeding Moscucci M et al.Eur Heart J 2003;24:
41 Predictors of Major Bleed Variables Overall UA STEMI NSTEMIAge (per 10 year ↑) x x x xFemale gender x x xHistory of renal insufficiency x x xHistory of bleeding x x x xKillip Class IV x MAP (per 20 mmHg ↓) x xIV Inotropics x x x xOther vasodilators x xThrombolytics x xDiuretics x x x xUnfractionated heparin x xIIb/IIIa receptor blockers x x xPA catheters x x x xPCI x x xThrombolytics and IIb/IIIa inhib x x xMoscucci M et al.Eur Heart J 2003;24:
42 In-Hospital Mortality Rates **********P<0.001Moscucci M et al.Eur Heart J 2003;24:
43 Outcome of “Low-risk” Patients with ACS Presentation with UA in the absence of dynamic ECG changes, no troponin elevation, no arrhythmia nor hypotensionAbnormal ECG in 38%,27% stress test, 37% echo, 52% angio6 month outcome:23% readmission12% revascularized3% deaths“Low-risk” is not no riskDevlin et al.Eur Heart J 2001;22(Abstr Suppl):525.
44 Evidence Based Medicine Total Population = 9,980ST MI Non- ST MI UA % of pts who areTherapy (n=2,501) (n=2,504) (n=3,631) eligibleASA X X XB blocker X XACE-I X XReperfusion XGP IIb/IIIa/LMWH X XGranger CB et al. J Am Coll Cardiol 2001;37(2 Suppl A):503A.
45 GRACE: Use of EBM in “Eligible” Patients 14%PTCA14%IIb/IIIa56%lytics48%LMWHn=5,373n=4,480n=3,254n=1,963n=4112Granger CB et al. J Am Coll Cardiol 2001;37(2 Suppl A):503A.
46 Management of acute coronary syndromes Management of acute coronary syndromes. variations in practice and outcome: Findings from the Global Registry of Acute Coronary Events (GRACE)K.A.A. Fox, S.G. Goodman, W. Klein, D. Brieger, P.G. Steg, O. Dabbous and Á. Avezum for the GRACE InvestigatorsEur Heart J 2002;23:
47 Geographic Practice Variation: Discharge Medication AT/AC, antithrombin or anticoagulantFox KAA et al. Eur Heart J 2002;23:
48 n=3420 of 8213 with CK, CK-MB & troponin measurements Increase in Diagnosis of MI Utilizing Troponinn=3420 of 8213 with CK, CK-MB & troponin measurementsThe most common diagnosis for patients with ACS enrolled in the GRACE study is UA, with around one-third of patients hospitalized with the condition. The second most common category of ACS is STEMI at 31%, followed by NSTEMI at 28%. A minority of patients were diagnosed with ‘other cardiac’ or ‘noncardiac’ diagnoses.Goodman SG et al. J Am Coll Cardiol 2001;37(2 Suppl A):358A.
49 In-Hospital Mortality OR & 95% CIn=1111*( )n=900n=124*( )( )The most common diagnosis for patients with ACS enrolled in the GRACE study is UA, with around one-third of patients hospitalized with the condition. The second most common category of ACS is STEMI at 31%, followed by NSTEMI at 28%. A minority of patients were diagnosed with ‘other cardiac’ or ‘noncardiac’ diagnoses.Goodman SG et al. J Am Coll Cardiol 2001;37(2 Suppl A):358A .*p<0.05
50 Impact of Aspirin on Presentation and Hospital Outcomes in Patients with Acute Coronary Syndromes (The Global Registry of Acute Coronary Events [GRACE])Frederick A. Spencer, Jose J. Santopinto, Joel M. Gore, Robert J. Goldberg, Keith A.A. Fox, Mauro Moscucci, Kami White, and Enrique P. GurfinkelAm J Cardiol 2002;90:
52 Type of ACS and Hospital Mortality in Patients with History of CAD Stratified By Prior ASA Impact of prior ASA on:STEMI 0.52 (0.44,0.61)*Death 0.69 (0.5,0.95)***Controlled for age, sex, medical hx, prior therapies, in hospital therapies**Controlled for above plus MI type
53 Type of ACS and Hospital Mortality in Patients without History of CAD Stratified By Prior ASA Impact of prior ASA on:STEMI 0.35 (0.30,0.40)*Death 0.77 (0.55,1.07)***Controlled for age, sex, medical hx, prior therapies, in hospital therapies** Controlled for above plus MI type
54 Association of Statin Therapy with Outcomes of Acute Coronary Syndromes: The GRACE Study Frederick A. Spencer, Jeanna Allegrone, Robert J. Goldberg, Joel M. Gore, Keith A.A. Fox, Christopher B. Granger, Rajendra H. Mehta and David Brieger for the GRACE Investigators*Ann Intern Med 2004;140:
55 Prior and Early Utilization of Statins in Patients with ACS: GRACE Ann. Intern Med. 2004;140:
56 Final Diagnosis of ACS Patients According to Previous Treatment with Statins *Multivariate analysis: Prior statin users less likely to present with STEMI -OR 0.79 (0.71,0.88)Ann. Intern Med. 2004;140:
57 Hospital Outcomes of ACS Patients Stratified by Statin Use Outcome Prior statins Prior & Hospital Hospital Statins Only Statin OnlyDeath (0.91,2.14) (0.16,0.25) 0.38 (0.30,0.48)Recurrent MI 0.69 (0.43,1.11) (0.75,1.07) 1.22 (1.08,1.37)Stroke (0.43,2.73) (0.42, 1.12) 0.80 (0.57, 1.14)Composite (0.74,1.41) (0.56,0.77) (0.78,0.97)*Compared to patients never receiving statinsAnn. Intern Med. 2004;140:
58 Comparison of Outcomes of Patients With Acute Coronary Syndromes With and Without Atrial FibrillationRajendra H. Mehta, Omar H. Dabbous, Christopher B. Granger, Polina Kuznetsova, Eva M. Kline-Rogers, Frederick A. Anderson, Jr., Keith A.A. Fox, Joel M. Gore, Robert J. Goldberg and Kim A. Eagle for the GRACE InvestigatorsAnn J Cardiol 2003;92:
59 Adjusted ORs for Hospital Events in Patients with ACS and New-Onset Atrial Fibrillation AF BetterAF WorseMajor bleedStrokeCardiac arrestPulmonary edemaShockDeathOdds RatioAm J Cardiol 2003;92(9):1031-6
60 Adjusted ORs for Hospital Events in Patients with ACS and Previous Atrial FibrillationAF BetterAF WorseMajor bleedStrokeCardiac arrestPulmonary edemaShockDeathOdds RatioAm J Cardiol 2003;92(9):1031-6
61 Determinants and Prognostic Impact of Heart Failure Complicating Acute Coronary Syndromes: Observations From the Global Registry of Acute Coronary Events (GRACE)Philippe Gabriel Steg, Omar H. Dabbous, Laurent J. Feldman, Alain Cohen-Solal, Marie-Claude Aumont, José López-Sendón, Andrzej Budaj, Robert J. Goldberg, Werner Klein, Frederick A. Anderson, Jr, for the Global Registry of Acute Coronary Events (GRACE) InvestigatorsCirculation. 2004;109:
62 Impact of Heart Failure on Admission on Hospital Mortality >75 years65-74 years55-64 years<55 years3.1 (2.4,3.9)3.3 (2.3,4.8)5.0 (2.9,8.3)10.1 (5.3,19.2)Lower oddsratio for death Higher odds of death*Relative to patients without HFCirculation 2004;109:
63 Death Rates from Hospital Admission to 6-Month Follow-Up for Patients According to Timing of Heart FailureCirculation 2004;109:
64 Hospital Case-Fatality Rates According to Development of Heart Failure Group HF (+) HF (-)All patients 12.0% 2.9%STEMI 16.5% 4.1%Non-STEMI 10.3% 3.0%Unstable angina % 1.6%Circulation 2004;109:
65 Stenting and Glycoprotein IIb/IIIa Inhibition in Patients With Acute Myocardial Infarction Undergoing Percutaneous Coronary Intervention: Findings From the Global Registry of Acute Coronary Events (GRACE)Gilles Montalescot, Frans Van de Werf, Dietrich C. Gulba, Àlvaro Avezum, David Brieger, Brian M. Kennelly, Tomasz Mazurek, Frederick Spencer, Kami White, and Joel M. Gore for the GRACE InvestigatorsCatheterization & Cardiovascular Interventions. 60: (2003)
66 Probability of Survival at 6 Months (all PCI) Death rates:+GP +stent 7.3% +GP –stent 12.8%-GP +stent 6.7% -GP – stent 14.4%Montalescot G et al.Catheter Cardiovasc Interv 2003;60:360-7.
67 Probability of Survival at 6 Months (Primary PCI) Death rates:+GP +stent 7.7% +GP –stent 7.4%-GP +stent 8.7% -GP –stent 20.1%Montalescot G et al.Catheter Cardiovasc Interv 2003;60:360-7.
68 Six-Month Outcomes in a Multinational Registry of Patients Hospitalized With an Acute Coronary Syndrome (The Global Registry of Acute Coronary Events [GRACE])Robert J. Goldberg, Kristen Currie, Kami White, David Brieger, Phillippe Gabriel Steg, Shaun G. Goodman, Omar Dabbous, Keith A.A. Fox and Joel M. Gore for the GRACE InvestigatorsAm J Cardiol 2004;93:
73 Survival Rate 6 Months Post Discharge for STEMI, NSTEMI, and UA Patients Goldberg RJ et al.Am J Cardiol 2004;93:
74 Factors Associated With An Increased Risk of Post-Discharge Death Characteristic STEMI Non-STEMIAge (yrs) HR % CI HR % CI>Medical historyHFMITIA/StrokeHospital complicationsCardiogenic shockHFStrokeGoldberg RJ et al.Am J Cardiol 2004;93:
75 Factors Associated with an Increased Risk of Post-Discharge Death in Patients with UACharacteristicAge (yrs) HR % CIMedical historyHFMIPCIHospital complicationsCardiogenic shockHFGoldberg RJ et al.Am J Cardiol 2004;93:
76 From guidelines to clinical practice: the impact of hospital and geographical characteristics on temporal trends in the management of acute coronary syndromes: The Global Registry of Acute Coronary Events (GRACE)Keith A.A. Fox, Shaun G. Goodman, Frederick A. Anderson Jr., Christopher B.Granger, Mauro Moscucci, Marcus D. Flather , Frederick Spencer, Andrzej Budaj, Omar H. Dabbous, Joel M. Gore on behalf of the GRACE InvestigatorsEuropean Heart Journal 2003;24:
93 Unique Features of GRACE Multi-national perspectiveFull spectrum of coronary syndromesIncreased data on demographics, presentation, management and outcomeRegular audits of data qualityFeedback to participating sites6-month follow-up