Global%20Registry%20of%20Acute%20Coronary%20Events%20Assessing%20Today

1
Global Registry of Acute Coronary
EventsAssessing Todays Practice Patterns to
Enhance Tomorrows Care

• 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 ACS
• Generalizable patient inclusion criteria
• In-hospital and 6-month follow-up
• Representative of the catchment population
  (clusters of hospitals)
• Full spectrum of hospitals and facilities
• Training, audit and quality control

3
International Scientific Advisory Committee
International Advisory Committee
Americas clusters Chair JM Gore
European clusters Chair KAA Fox
8 advisors
8 advisors
40 subsite cardiologists
40 subsite cardiologists
4
Scientific Advisory Committee
Co-Chairs Keith AA Fox, UK Joel M Gore, USA
Publications Kim A Eagle, USA Co-Chairs Ph
Gabriel Steg, France
Study Co-ordination Fred Anderson, University
of Massachusetts
Argentina Enrique Gurfinkel Australia/New
Zealand David Brieger Austria Georg Gaul Belgium
Frans J Van de Werf Brazil Álvaro Avezum Canada
Shaun Goodman
Germany Dietrich C Gulba Italy Giancarlo
Agnelli France Gilles Montalescot Ph Gabriel
Steg Poland Andrzej Budaj Spain José López-Sendón
United Kingdom Keith AA Fox Marcus Flather United
States Frederick A Anderson Kim A Eagle Robert J
Goldberg Joel M Gore Christopher B Granger Brian
M Kennelly
5
Objectives of GRACE

• Identify opportunities to improve the quality of
  care for patients with ACS
• Describe diagnostic treatment strategies,
  hospital post-discharge outcomes
• Develop hypotheses for future clinical research
• Disseminate findings to a wider audience

6
Core GRACE Study Design

• 100 hospitals in 14 countries
• Europe, North South America, Australia, New
  Zealand
• Population-based clusters with community
  hospitals and referral centres
• First 10-20 consecutive cases per centre/month
  qualifying symptoms PLUS evidence of CAD
• Random audit of all centres 3 year cycle

7
Cluster Strategy for Study Sites
Population-Based Design
2
1
3
18 advisory committee members
100 hospitals 10,000 ACS patients/year
4
6
5
8
Multinational Site Network
Argentina 6 sites Australia 7 sites Austria
6 site Belgium 6 sites Brazil 7 sites Canada 6
sites France 6 sites
Germany 5 sites Italy 5 sites New Zealand 2
sites Poland 6 sites Spain 4 sites UK 5
sites USA 18 sites
9
89 Active Core Study Sites 17 Clusters in 14
Countries
10
Status of 17 Core Clusters

• 70,359 cases enrolled
• 85 six-month follow-up

Q4-2007
11
The Big PictureCore GRACE GRACE2
GRACE Core 70,359 patients 89 hospitals 14
countries
GRACE2 31,982 patients 158 hospitals 23
countries
12
247 Core GRACE GRACE2 Study Sites in 30
Countries
30 countries 16 GRACE2 7 core GRACE 7 both
13
Status December 31, 200789 Core 158 Expanded
Sites

• 30 countries
• 247 hospitals
• 102,341 cases

Q4-2007
14
Internet Websitewww.outcomes.org/grace
15
Hospital CharacteristicsQ4-2001 vs. Current
Quarter

• 
  Q4-2001
  Q4-2007
• Number of Hospitals 109 89
• Coronary care unit 94 98
• Emergency department 86 88
• Cardiac catheterization laboratory 65
  72
• Open heart surgery 43 45
• Hospital beds (mean) 416
  523
• Coronary care unit beds (mean) 10
  11
• ACS admissions (mean, per year) 487
  585

Q4-2007
16
70,359 Cases Enrolledas of December 31, 2007
Q4-2007
17
Classification of Cases
Q4-2007
18
Hospital Discharge Status

• STEMI NSTEMI UA
• Death 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

Missing diagnosis in 236 patients
Admission 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 2002231177-89.
20
Baseline Characteristics

• STEMI
  NSTEMI UA
  (n 13,862) (11,316)
  (12,509)
• Median age (years) 65 68 66
• Male () 70 66 64
• Prior history ()
• Angina 43 56 78
• Myocardial infarction 20 32 41
• PCI/CABG 8/5 15/14 25/19
• Smoking 62 57 55
• Diabetes mellitus 21 28 26
• Hypertension 52 62 66
• Hyperlipidemia 38 47 54
• Participant in clin trial () 11 7 7

21
Hospital Treatment According to Admission
Diagnosis
MI
UA ? MI Chest pain n
16,304 15,266
3,474 3,266 ACE
inhibitors 69 56 56
55 Aspirin 94 92 92
92 ?-blockers 83 81 81
79 Ca2 blockers 15 34 30
29 Gp IIb/IIIa no PCI 5 4 7
7 Gp IIb/IIIa with PCI 26
11 15 18 LMWH
52 64 40
40 UFH 59 43 51
51 Thrombolytic agents 35 2 3 3
22
Diagnostic Procedures
23
Hospital Cardiac Interventions According to Final
Diagnosis
Intervention STEMI
NSTEMI UA n
13,862 11,316
12,509 Cardiac catheterization
62 57 49 PCI 45 31 23 CABG 4 7 6
24
Treatments at Discharge
STEMI
NSTEMI UA n
13,862 11,316
12,509 ACE inhibitors
67 56 52 Aspirin 92 89 88 ?-blockers
78 76 72 Ca2 blockers 10 20 31 Statins
63 59 57 Warfarin 8 7 7
25
Hospital Outcome by Final Diagnosis
26
Hospital Outcomes
lt0.0001
10.7
lt0.0001
5.6
5.6
4.0
Lankes W et al.Eur Heart J 200223(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 Investigators Lancet 2002359373-77
29
Missed Opportunities for Reperfusion
ST ? or LBBB, lt12 hrs from onset, no
contraindications ANC () US
() AB () EUR () n 269
327 339 739 PCI alone
1.1 17.7 13.9
16.2 Lytic alone 66.9 30.6
53.1 49.4 Both 2.2
18.7 5.0 4.9 Neither
29.7 33.0 28.0
29.5 AB, Argentina/Brazil ANC, Australia/New
Zealand/Canada EUR, Europe US, United States
Eagle KA et al. Lancet 2002359373-7.
30
Independent Predictors of No Reperfusion
Variable OR (95
CI) Prior CABG 2.28 (1.35 -
3.87) History of diabetes 1.46
(1.11 -1.94) History of congestive heart
failure 2.92 (1.84 - 4.67) Presentation
without chest pain 2.23 (2.13 - 4.89)
Age ?75 years 2.37 (1.82 - 3.08)
As compared to the lt55 years age group
Eagle KA et al. Lancet 2002359373-7.
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 Investigators Am Heart J
2003146999-1006.
33
Geographic Practice Variation
Budaj A et al. Am Heart J 2003146999-1006.
34
Antithrombotic Rx Used
Cannon CP et al.Eur Heart J 200122(Abstr
Suppl)592.
35
Incidence of Major Bleeding
Cannon CP et al.Eur Heart J 200122(Abstr
Suppl)592.
36
Multivariate Adjusted Odds of Major Hemorrhage
Major hem 3.9 2.4 8.3 2.9
UFH LMWH UFH IIb/IIIa LMWH IIb/IIIa
OR0.55 Plt0.001
OR2.26
0 0.5 1 2 3
Lower
Higher
Cannon CP et al.Eur Heart J 200122(Abstr
Suppl)592.
37
Safety Events
?
Cannon CP et al.Eur Heart J 200122(Abstr
Suppl)592.
38
Major Cardiac Events
Cannon CP et al.Eur Heart J 200122(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 Investigators European
Heart Journal 2003241815-1823
40
Incidence of Major Bleeding
Moscucci M et al.Eur Heart J 2003241815-23.
41
Predictors of Major Bleed
Variables Overall UA STEMI NSTEMI Age (per 10
year ?) x x x x Female gender x x x History of
renal insufficiency x x x History of
bleeding x x x x Killip Class IV xMAP (per 20
mmHg ?) x x IV Inotropics x x x x Other
vasodilators x x Thrombolytics x x Diuretics x
x x x Unfractionated heparin x x IIb/IIIa
receptor blockers x x x PA catheters x x x x PCI
x x x Thrombolytics and IIb/IIIa inhib x x x
Moscucci M et al.Eur Heart J 2003241815-23.
42
In-Hospital Mortality Rates




Plt0.001
Moscucci M et al.Eur Heart J 2003241815-23.
43
Outcome of Low-risk Patients with ACS

• Presentation with UA in the absence of dynamic
  ECG changes, no troponin elevation, no
  arrhythmia nor hypotension
• Abnormal ECG in 38,
• 27 stress test, 37 echo, 52 angio
• 6 month outcome
• 23 readmission
• 12 revascularized
• 3 deaths
• Low-risk is not no risk

Devlin et al.Eur Heart J 200122(Abstr
Suppl)525.
44
Evidence Based Medicine
Total Population 9,980
ST ? MI Non- ST ? MI UA of pts who are
Therapy (n2,501) (n2,504) (n3,631) eligible
ASA X X X B blocker X X ACE-I X X Reperf
usion X GP IIb/IIIa/LMWH X X
Granger CB et al. J Am Coll Cardiol 200137(2
Suppl A)503A.
45
GRACE Use of EBM in Eligible Patients
14 PTCA
14 IIb/IIIa
56 lytics
48 LMWH
n5,373
n4,480
n3,254
n1,963
n4112
Granger CB et al. J Am Coll Cardiol 200137(2
Suppl A)503A.
46
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 Investigators Eur Heart J
2002231177-1189
47
Geographic Practice VariationDischarge
Medication
Plt0.01 AT/AC, antithrombin or anticoagulant
Fox KAA et al. Eur Heart J 2002231177-89.
48
Increase in Diagnosis of MI Utilizing Troponin
Goodman SG et al. J Am Coll Cardiol 200137(2
Suppl A)358A.
49
In-Hospital Mortality
OR 95 CI
n1111

(3.3 - 10.1)
n900
n124

(1.6 - 5.7)
(0.6 - 7.4)


Goodman SG et al. J Am Coll Cardiol 200137(2
Suppl A)358A .
plt0.05
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. Gurfinkel Am J Cardiol
2002901056-1061
51
Impact of Prior ASA on ACS GRACE

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 2004140857-866
55
Prior and Early Utilization of Statins in
Patients with ACS GRACE
Patients
Ann. Intern Med. 2004140856-866.
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. 2004140856-866.
57
Hospital Outcomes of ACS Patients Stratified by
Statin Use
Outcome Prior statins Prior Hospital
Hospital Statins Only
Statin Only Death 1.39
(0.91,2.14) 0.20 (0.16,0.25) 0.38
(0.30,0.48) Recurrent MI 0.69 (0.43,1.11)
0.90 (0.75,1.07) 1.22 (1.08,1.37) Stroke 1.08
(0.43,2.73) 0.68 (0.42, 1.12) 0.80 (0.57,
1.14) Composite 1.02 (0.74,1.41) 0.66
(0.56,0.77) 0.87 (0.78,0.97)
Compared to patients never receiving statins
Ann. Intern Med. 2004140856-866.
58
Comparison of Outcomes of Patients With Acute
Coronary Syndromes With and Without Atrial
Fibrillation Rajendra 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 Investigators Ann J
Cardiol 2003921031-1036
59
Adjusted ORs for Hospital Events in Patients with
ACS and New-Onset Atrial Fibrillation
AF Better
AF Worse
Major bleed Stroke Cardiac arrest Pulmonary
edema Shock Death
?
?
?
?
?
?
0 0.5 1 1.5 2 2.5
3 3.5 4
Odds Ratio
Am J Cardiol 200392(9)1031-6
60
Adjusted ORs for Hospital Events in Patients with
ACS and Previous Atrial Fibrillation
AF Better
AF Worse
Major bleed Stroke Cardiac arrest Pulmonary
edema Shock Death
?
?
?
?
?
?
0 0.5 1
1.5 2 2.5
Odds Ratio
Am J Cardiol 200392(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)
Investigators Circulation. 2004109494-499
62
Impact of Heart Failure on Admission on Hospital
Mortality
gt75 years 65-74 years 55-64 years lt55 years
3.1 (2.4,3.9)
3.3 (2.3,4.8)
5.0 (2.9,8.3)
10.1 (5.3,19.2)
1 10
20
Lower odds ratio for death Higher odds of
death
Relative to patients without HF
Circulation 2004109494-499.
63
Death Rates from Hospital Admission to 6-Month
Follow-Up for Patients According to Timing of
Heart Failure

Circulation 2004109494-499.
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 6.7 1.6
Circulation 2004109494-499.
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 Investigators Catheterizati
on Cardiovascular Interventions. 60360-367
(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
200360360-7.
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
200360360-7.
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
Investigators Am J Cardiol 200493288-293
69
Six-Month Follow-Up
STEMI NSTEMI UA Death 5
(480/9414) 6 (496/7977) 4 (349/9357) Stroke 1
(110/9173) 1 (103/7749) 1 (79/9176) Rehospitaliz
ed 18 (1619/9147) 19 (1501/7721) 19
(1761/9150) Excluding events that occurred in
hospital
Goldberg RJ et al.Am J Cardiol 200493288-93.
70
Discharge to 6 Month Outcomes Cardiac
Interventions
Scheduled and unscheduled procedures
Goldberg RJ et al.Am J Cardiol 200493288-93.
71
6 Month Follow-up
Cannon CP et al.Eur Heart J 200122(Abstr
Suppl)592.
72
Total Outcomes Admission to 6 Months
73
Survival Rate 6 Months Post Discharge for STEMI,
NSTEMI, and UA Patients
Goldberg RJ et al.Am J Cardiol 200493288-93.
74
Factors Associated With An Increased Risk of
Post-Discharge Death
Characteristic STEMI Non-STEMI Age (yrs)
HR 95 CI HR 95 CI 65-74 3.48
2.00-6.06 2.17 1.27-3.72 gt75 8.95
5.28-15.20 5.30 3.19-8.80 Medical history
HF 2.21 1.61-3.04 2.20 1.71-2.84 MI 1.69
1.28-2.22 TIA/Stroke 1.37
1.03-1.84 Hospital complications Cardiogenic
shock 1.94 1.20-3.15 HF 2.16 1.65-2.83 1.91
1.49-2.44 Stroke 2.51 1.32-4.78
Goldberg RJ et al.Am J Cardiol 200493288-93.
75
Factors Associated with an Increased Risk of
Post-Discharge Death in Patients with UA
Characteristic Age (yrs) HR 95 CI
55-64 3.34 1.81-6.19 65-74 5.29
2.88-9.72 Medical history HF 2.23
1.61-3.08 MI 1.44 1.09-1.91 PCI 0.52
0.35-0.77 Hospital complications
Cardiogenic shock 4.01 1.73-9.28 HF 1.67
1.17-2.37
Goldberg RJ et al.Am J Cardiol 200493288-93.
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
Investigators European Heart Journal
2003241414-1424
77
Temporal Trends in ACS Diagnostic Categories
78
Temporal Trends STEMI In-hospital Therapies
Fox KAA et al. Eur Heart J 2003241414-24.
without PCI
79
Temporal Trends STEMI Reperfusion
Fox KAA et al. Eur Heart J 2003241414-24.
within 12 h
80
Temporal Trends NSTEMIIn-hospital Therapies
Fox KAA et al. Eur Heart J 2003241414-24.
81
GRACE Palm Pilot SoftwareIn-hospital,
6-monthsDeath, Death/MI Prediction Model
82
(No Transcript)
83
GRACE PDA Software
84
GRACE PDA Software
85
At Admission Risk Model
86
At Discharge Risk Model
87
GRACE Publications
88
Abstract Acceptance Rate (1999 to 2007)
Number of abstracts accepted 111
89
Manuscript Status
90
GRACE Quarterly Reports to Investigators
91
Quarterly ReportCurrent Quarter vs. Overall
92
Quarterly ReportTemporal Trends
93
Unique Features of GRACE

• Multi-national perspective
• Full spectrum of coronary syndromes
• Increased data on demographics, presentation,
  management and outcome
• Regular audits of data quality
• Feedback to participating sites
• 6-month follow-up