Global Registry of Acute Global Registry of Acute Coronary Events Coronary Events Assessing Today’s Practice Patterns to Assessing Today’s Practice Patterns to Enhance Tomorrow’s Care Enhance Tomorrow’s Care Supported by an unrestricted educational grant Supported by an unrestricted educational grant from from sanofi-aventis to the Center for Outcomes sanofi-aventis to the Center for Outcomes Research Research University of Massachusetts Medical School University of Massachusetts Medical School
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Global Registry of Acute Global Registry of Acute Coronary EventsCoronary Events
Assessing Today’s Practice Patterns to Assessing Today’s Practice Patterns to Enhance Tomorrow’s CareEnhance Tomorrow’s Care
Supported by an unrestricted educational grant from Supported by an unrestricted educational grant from sanofi-aventis to the Center for Outcomes Research sanofi-aventis to the Center for Outcomes Research
University of Massachusetts Medical SchoolUniversity of Massachusetts Medical School
What is GRACE?What is GRACE?
Global Registry of Acute Coronary EventsGlobal Registry of Acute Coronary Events Largest multinational registry covering the full Largest multinational registry covering the full
spectrum of ACSspectrum of ACS Generalizable patient inclusion criteria Generalizable patient inclusion criteria In-hospital and 6-month follow-upIn-hospital and 6-month follow-up Representative of the catchment population: Representative of the catchment population:
(clusters of hospitals)(clusters of hospitals) Full spectrum of hospitals and facilitiesFull spectrum of hospitals and facilities Training, audit and quality controlTraining, audit and quality control
International Scientific International Scientific Advisory CommitteeAdvisory Committee
International Advisory CommitteeInternational Advisory Committee
ArgentinaArgentina Enrique GurfinkelEnrique GurfinkelAustralia/New ZealandAustralia/New ZealandDavid BriegerDavid BriegerAustriaAustriaGeorg GaulGeorg GaulBelgium Belgium Frans J Van de WerfFrans J Van de WerfBrazil Brazil Álvaro AvezumÁlvaro AvezumCanada Canada Shaun GoodmanShaun Goodman
Germany Germany Dietrich C GulbaDietrich C GulbaItalyItalyGiancarlo AgnelliGiancarlo AgnelliFranceFranceGilles MontalescotGilles MontalescotPh Gabriel StegPh Gabriel StegPolandPolandAndrzej BudajAndrzej BudajSpainSpain José López-SendónJosé López-Sendón
United KingdomUnited KingdomKeith AA FoxKeith AA FoxMarcus FlatherMarcus FlatherUnited StatesUnited StatesFrederick A AndersonFrederick A AndersonKim A EagleKim A EagleRobert J GoldbergRobert J GoldbergJoel M GoreJoel M GoreChristopher B GrangerChristopher B GrangerBrian M KennellyBrian M Kennelly
Co-ChairsCo-Chairs Keith AA Fox, UKKeith AA Fox, UKJoel M Gore, USAJoel M Gore, USA
Publications Publications Kim A Eagle, USAKim A Eagle, USACo-ChairsCo-Chairs Ph Gabriel Steg, FrancePh Gabriel Steg, France
Study Co-ordinationStudy Co-ordination Fred Anderson, University of Massachusetts Fred Anderson, University of Massachusetts
Objectives of GRACEObjectives of GRACE
Identify opportunities to improve the quality Identify opportunities to improve the quality of care for patients with ACSof care for patients with ACS
Hospital Discharge StatusHospital Discharge Status
STEMISTEMI NSTEMI UA NSTEMI UA
DeathDeath 7%7% 4%4% 3%3%
HomeHome 77%77% 78%78% 87%87%
Transfer Transfer ** 10%10% 12%12% 9%9%
OtherOther 6%6% 6%6% 2%2%
**Transfer to another acute care hospital.Transfer to another acute care hospital.
Q4-2007Q4-2007
*Missing diagnosis in 236 patients
UAN=4999(44%)
‘Rule-out’ MIN=957(9%)
Unspecified chest pain
N=745(7%)
Other cardiacN=381(3%)
Non-cardiacN=125(1%)
STEMIN=3419(30%)
Non-STEMIN=2893(25%)
Unstable anginaN=4397(38%)
Other cardiacN=508(4%)
Non-cardiacN=326(3%)
MIN=4100(36%)
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.
Admission versus Final Admission versus Final DiagnosisDiagnosis
Fox KAA et al.Eur Heart J 2002;23:1177-89.Fox KAA et al.Eur Heart J 2002;23:1177-89.
Hospital Outcome by Hospital Outcome by Final DiagnosisFinal Diagnosis
Hospital OutcomesHospital Outcomes
0
4
8
12
Death Major bleed
Pat
ien
ts (
%)
Elderly patients (>=75)
Younger patients (65-<75)10.7
5.6
4.0
5.6
<0.0001
<0.0001
Lankes W et al.Eur Heart J 2002;23(Abstr Suppl):502.Lankes W et al.Eur Heart J 2002;23(Abstr Suppl):502.
What proportion of eligible patients What proportion of eligible patients receive reperfusion therapy?receive reperfusion therapy?
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 2002;359:373-77
Missed Opportunities for Missed Opportunities for ReperfusionReperfusion
ST ↑ or LBBB, <12 hrs from onset, no contraindications
Geographical Variation: Geographical Variation: Admission to Hospitals Admission to Hospitals with/without Access to Cath Labwith/without Access to Cath Lab
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 2003;146:999-1006.
3733
13
92
178
58
92
30
15
65
91
24
9
39
95
0
20
40
60
80
100
PCI GP IIb/IIIa LMWH ASA
Pat
ien
ts (
%)
United States
Australia/New Zealand/Canada
Europe
Argentina/Brazil
Geographic Practice VariationGeographic Practice Variation
Budaj A et al. Am Heart J 2003;146:999-1006.Budaj A et al. Am Heart J 2003;146:999-1006.
Antithrombotic Rx UsedAntithrombotic Rx Used
LMWH 46%
UFH 30%
UFH + llb/IIIa
4%
LMWH + llb/IIIa
2%
None 18%
Cannon CP et al.Eur Heart J 2001;22(Abstr Suppl):592.Cannon CP et al.Eur Heart J 2001;22(Abstr Suppl):592.
Incidence of Major BleedingIncidence of Major Bleeding
3.9
2.4
8.3
2.9
0
3
6
9
Major bleed
Pat
ien
ts (
%)
UFH
LMWH
UFH + IIb/IIIa
LMWH + IIb/IIIa
Cannon CP et al.Eur Heart J 2001;22(Abstr Suppl):592.Cannon CP et al.Eur Heart J 2001;22(Abstr Suppl):592.
Multivariate Adjusted Odds of Multivariate Adjusted Odds of Major HemorrhageMajor Hemorrhage
0 0.5 1 2 3Lower Higher
Major hemMajor hem 3.9%3.9%
2.4%2.4%
8.3%8.3%
2.9%2.9%
UFHUFH
LMWHLMWH
UFH +UFH +IIb/IIIaIIb/IIIa
LMWH +LMWH +IIb/IIIaIIb/IIIa
OR=0.55OR=0.55P<0.001P<0.001
OR=2.26OR=2.26
Cannon CP et al.Eur Heart J 2001;22(Abstr Suppl):592.Cannon CP et al.Eur Heart J 2001;22(Abstr Suppl):592.
Safety EventsSafety Events
0.1
0.7
1.2
0
0.6 0.7
0.3
0.6
0 0
2.9
1.5
0
1
2
3
ICH Stroke Plts
Pa
tie
nts
(%
)
UFHLMWHUFH + IIb/IIIaLMWH + IIb/IIIa
Cannon CP et al.Eur Heart J 2001;22(Abstr Suppl):592.Cannon CP et al.Eur Heart J 2001;22(Abstr Suppl):592.
Major Cardiac EventsMajor Cardiac Events
5
10.6
2.9
6.65
11.3
13.8
4.4
6.3
2.9
9.9
12.4
0
5
10
15
Death MI Death/MI
Pat
ien
ts (
%)
UFH
LMWH
UFH + IIb/IIIa
LMWH + IIb/IIIa
Cannon CP et al.Eur Heart J 2001;22(Abstr Suppl):592.Cannon CP et al.Eur Heart J 2001;22(Abstr Suppl):592.
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 2003;24:1815-1823
Incidence of Major BleedingIncidence of Major Bleeding
3.9
2.3
4.7 4.8
0
1
2
3
4
5
6
Major Bleed
% o
f P
ati
en
ts
Overall UA
NSTEMI STEMI
Moscucci MMoscucci M et al.et al.Eur Heart J 2003;24:1815-23.Eur Heart J 2003;24:1815-23.
Predictors of Major Bleed Predictors of Major Bleed VariablesVariables OverallOverall UAUA STEMISTEMI NSTEMINSTEMI
Age (per 10 year Age (per 10 year ↑)↑) xx xx xx xxFemale genderFemale gender xx xx xxHistory of renal insufficiencyHistory of renal insufficiency xx xx xxHistory of bleedingHistory of bleeding xx xx xx xxKillip Class IVKillip Class IV xxMAP (per 20 mmHg MAP (per 20 mmHg ↓)↓) xx xxIV InotropicsIV Inotropics xx xx xx xx
Other vasodilatorsOther vasodilators xx xx
ThrombolyticsThrombolytics xx xxDiureticsDiuretics xx xx xx xxUnfractionated heparinUnfractionated heparin xx xxIIb/IIIa receptor blockersIIb/IIIa receptor blockers xx xx xxPA cathetersPA catheters xx xx xx xxPCIPCI xx xx xxThrombolytics and IIb/IIIa inhibThrombolytics and IIb/IIIa inhib xx xx xx
Moscucci MMoscucci M et al.et al.Eur Heart J 2003;24:1815-23.Eur Heart J 2003;24:1815-23.
Moscucci MMoscucci M et al.et al.Eur Heart J 2003;24:1815-23.Eur Heart J 2003;24:1815-23.
Outcome of “Low-risk” Outcome of “Low-risk” Patients with ACSPatients with ACS
Presentation with UA in the absence of dynamic Presentation with UA in the absence of dynamic ECG changes, no troponin elevation, no arrhythmia ECG changes, no troponin elevation, no arrhythmia nor hypotensionnor hypotension
GP IIb/IIIa/LMWHGP IIb/IIIa/LMWH XX XXGranger CB et al. et al. J Am Coll CardiolJ Am Coll Cardiol 2001;37(2 Suppl A):503A. 2001;37(2 Suppl A):503A.
GRACE: Use of EBM in GRACE: Use of EBM in “Eligible” Patients“Eligible” Patients
93%
81%
64%70%
58%
71%
57%
89%
0%
20%
40%
60%
80%
100%
ASA B-blocker ACE-I Reperf LMWH/IIb/IIIa
% I
deal
Use
In-hosp
Discharge
14% PTCA
56% lytics
14% IIb/IIIa
48% LMWH
n=5,373 n=4,480 n=3,254 n=1,963 n=4112
Granger CB et al. et al. J Am Coll CardiolJ Am Coll Cardiol 2001;37(2 Suppl A):503A. 2001;37(2 Suppl A):503A.
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 2002;23:1177-1189
Geographic Practice Variation:Geographic Practice Variation:Discharge MedicationDischarge Medication
4753
94
4957
93
5450
94
53
26
93
0
20
40
60
80
100
ACE Statin AT/AC
Pat
ien
ts (
%)
United States
Australia/New Zealand/Canada
Europe
Argentina/Brazil
**P<0.01
AT/AC, antithrombin or anticoagulantFox KAA et al. Eur Heart J 2002;23:1177-89et al. Eur Heart J 2002;23:1177-89..
n=3420 of 8213 with CK, CK-MB
& troponin measurements
26
15
9
0
5
10
15
20
25
30
Troponin + in additionto CK ULN
Troponin + in additionto CK 2 x ULN
Troponin + in additionto CK-MB ULN
% In
cre
as
e in
Pa
tie
nts
w
ith
MI
Increase in Diagnosis of MI Increase in Diagnosis of MI Utilizing TroponinUtilizing Troponin
Goodman SG et al. et al. J Am Coll CardiolJ Am Coll Cardiol 2001;37(2 Suppl A):358A 2001;37(2 Suppl A):358A..
In-Hospital MortalityIn-Hospital Mortality
5.8
32.1
0
2
4
6
8
CK 2 x ULNTroponin–
CK 2 x ULNTroponin +
CK > 2 x ULNTroponin–
CK > 2 x ULNTroponin +
Od
ds
Ra
tio
(1.6 - 5.7)
(0.6 - 7.4)
(3.3 - 10.1)
*
OR & 95% CI
*p<0.05
n=900n=900n=124n=124
*
Goodman SG et al. et al. J Am Coll CardiolJ Am Coll Cardiol 2001;37(2 Suppl A):358A 2001;37(2 Suppl A):358A ..
n=1111n=1111
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 2002;90:1056-1061
77.8
18.1
74.5
18.5
70.3
18.3
69.5
25.4
0
20
40
60
80
100
Hx of CAD (n=4974) No Hx of CAD (n=6414)
Prior long-ASA use according to geographic region and history
Per
cen
tag
e
Australia/New Zealand/CanadaEurope
South AmericaUSA
Impact of Prior ASA on ACS: Impact of Prior ASA on ACS: GRACEGRACE
Type of ACS and Hospital Type of ACS and Hospital Mortality in Patients with History Mortality in Patients with History of CAD Stratified By Prior ASAof CAD Stratified By Prior ASA
Impact of Impact of prior ASA on:prior ASA on:– STEMI 0.52 STEMI 0.52
(0.44,0.61)*(0.44,0.61)*– Death 0.69 Death 0.69
(0.5,0.95)**(0.5,0.95)**15
28
58
3
26 29
45
7
0
20
40
60
80
STEMI NSTEMI UA Death
Prior ASA No prior ASA
*Controlled for age, sex, medical hx, prior therapies, in hospital therapies
**Controlled for above plus MI type
Type of ACS and Hospital Mortality Type of ACS and Hospital Mortality in Patients without History of CAD in Patients without History of CAD Stratified By Prior ASAStratified By Prior ASA
Impact of prior Impact of prior ASA on:ASA on:– STEMI 0.35 STEMI 0.35
(0.30,0.40)*(0.30,0.40)*– Death 0.77 Death 0.77
(0.55,1.07)**(0.55,1.07)**
25
31
44
5
51
2723
6
0
20
40
60
STEMI NSTEMI UA Death
Prior ASA No prior ASA
*Controlled for age, sex, medical hx, prior therapies, in hospital therapies
** Controlled for above plus MI type
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;140:857-866
0
2000
4000
6000
8000
10000
12000
14000
16000
18000
Prior Statins No Prior Statins
Hospital Statins No Hospital Statins
Pa
tient
sPrior and Early Utilization of Statins Prior and Early Utilization of Statins in Patients with ACS: GRACEin Patients with ACS: GRACE
Ann. Intern Med. 2004;140:856-866.Ann. Intern Med. 2004;140:856-866.
Final Diagnosis of ACS Patients Final Diagnosis of ACS Patients According to Previous Treatment According to Previous Treatment with Statinswith Statins
0
20
40
60
80
100
Previous Statin Use No Previous Statin Use
Pa
tie
nts
, %
St elevation MI* non-ST elevation MI Unstable angina
*Multivariate analysis: Prior statin users less likely to present with STEMI -OR 0.79 (0.71,0.88)
Ann. Intern Med. 2004;140:856-866.Ann. Intern Med. 2004;140:856-866.
Hospital Outcomes of ACS Hospital Outcomes of ACS Patients Stratified by Statin UsePatients 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)
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. 2004;140:856-866.Ann. Intern Med. 2004;140:856-866.
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 2003;92:1031-1036
Adjusted ORs for Hospital Adjusted ORs for Hospital Events in Patients with ACS and Events in Patients with ACS and New-Onset Atrial FibrillationNew-Onset Atrial Fibrillation
0 0.5 1 1.5 2 2.5 3 3.5 4
Odds Ratio
Major bleed
Stroke
Cardiac arrest
Pulmonary edema
Shock
Death
AF Better AF Worse
Am J Cardiol 2003;92(9):1031-6
Adjusted ORs for Hospital Events in Patients with ACS and Previous Atrial Fibrillation
0 0.5 1 1.5 2 2.5
Odds Ratio
Major bleed
Stroke
Cardiac arrest
Pulmonary edema
Shock
Death
AF Better AF Worse
Am J Cardiol 2003;92(9):1031-6
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. 2004;109:494-499
Impact of Heart Failure on Impact of Heart Failure on Admission on Hospital MortalityAdmission on Hospital Mortality
Death Rates from Hospital Admission Death Rates from Hospital Admission to 6-Month Follow-Up for Patients to 6-Month Follow-Up for Patients According to Timing of Heart FailureAccording to Timing of Heart Failure
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
Probability of Survival at Probability of Survival at 6 Months (all PCI)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.et al.Catheter Cardiovasc Interv 2003;60:360-7.
Probability of Survival at Probability of Survival at 6 Months (Primary PCI)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.et al.Catheter Cardiovasc Interv 2003;60:360-7.
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
Factors Associated with an Factors Associated with an Increased Risk of Post-Discharge Increased Risk of Post-Discharge Death in Patients with UADeath in Patients with UA
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 2003;24:1414-1424
Temporal Trends in Temporal Trends in ACS Diagnostic CategoriesACS Diagnostic Categories
Multi-national perspectiveMulti-national perspective Full spectrum of coronary syndromesFull spectrum of coronary syndromes Increased data on demographics, Increased data on demographics,
presentation, management and outcomepresentation, management and outcome Regular audits of data qualityRegular audits of data quality Feedback to participating sitesFeedback to participating sites 6-month follow-up6-month follow-up