ORIGINAL CONTRIBUTION

A Validated Prediction Model

for All Forms of Acute Coronary Syndrome
Estimating the Risk of 6-Month Postdischarge Death
in an International Registry
Kim A. Eagle, MD
Michael J. Lim, MD
Omar H. Dabbous, MD, MPH
Karen S. Pieper, MS
Robert J. Goldberg, PhD
Frans Van de Werf, MD, PhD
Shaun G. Goodman, MD, MSc
Christopher B. Granger, MD
P. Gabriel Steg, MD
Joel M. Gore, MD
Andrzej Budaj, MD, PhD
Alvaro Avezum, MD, PhD
Marcus D. Flather, MBBS, FRCP
Keith A. A. Fox, MB, ChB, FRCP
for the GRACE Investigators

LINICAL PREDICTION MODELS

may be helpful for medical

decision making1 as patients
judged to be at higher risk
may receive more aggressive surveillance and/or earlier treatment, while patients estimated to be at lower risk may
be reassured and managed less aggressively.2,3 By using simple yet valid risk
calculations, clinicians can accurately
advise patients about their likelihood
of an event, and how this likelihood
translates into treatment decisions.
The acute coronary syndrome (ACS)
encompasses a continuum of conditions ranging from ST-segment elevation myocardial infarction (STEMI) to
nonST-segment elevation myocardial
infarction (NSTEMI) and unstable an-

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 17142 patients presenting with an ACS from April 1, 1999, to March
31, 2002, and discharged alive, 15007 (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.
www.jama.com

JAMA. 2004;291:2727-2733
Author Affiliations: Department of Internal Medicine, University of Michigan Health System, Ann
Arbor (Drs Eagle and Lim); Department of Medicine,
University of Massachusetts Medical School,
Worcester (Drs Dabbous, Goldberg, and Gore);
Department of Medicine, Duke University Medical
Center, Durham, NC (Dr Granger and Ms Pieper);
Department of Cardiology, Universitair Ziekenhuis
Gasthuisberg, Leuven, Belgium (Dr Van de Werf );
Canadian Heart Research Centre and Terrence Donnelly Heart Centre, and Division of Cardiology, St
Michaels Hospital, University of Toronto, Toronto,
Ontario (Dr Goodman); Cardiology, Hopital Bichat,
Paris, France (Dr Steg); Postgraduate Medical
School, Grochowski Hospital, Warsaw, Poland (Dr
Budaj); Clinical Research Center, Education, and
Research Institute Hospital Albert Einstein, Sa o
Paulo, Brazil (Dr Avezum); Royal Brompton and

2004 American Medical Association. All rights reserved.

Harefield NHS Trust, London, England (Dr Flather);

and The University and The Royal Infirmary of Edinburgh, Edinburgh, Scotland (Dr Fox).
Financial Disclosures: Dr Eagle receives research grants
from Aventis, BlueCross BlueShield of Michigan, Pfizer,
the Mardigian Foundation, and the Varbedian Fund
for Aortic Research, and is a consultant for the National Institutes of Health, the Heart, Lung, and Blood
Institute, and Sanofi. Dr Flather received an honorarium for participation in the GRACE program and
has received speaker fees for meetings and research
grants for studies supported by Aventis Pharma. Dr
Fox has received funding support and an educational
grant from Aventis for the GRACE study.
Corresponding Author: Kim A. Eagle, MD, Department of Internal Medicine, University of Michigan Cardiovascular Center, 300 N Ingalls, 8B02, Ann Arbor,
MI 48109-0477 ([email protected]).

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2727

PREDICTION MODEL FOR ACUTE CORONARY SYNDROMES

gina.1,4-8 Numerous risk-prediction models for differing outcomes exist for the
different types of ACS.5,9 Most models
have been developed from large randomized clinical trial populations in which

the generalizability to risk prediction in

the average clinicians experience is questionable.6-10
We were interested in developing a
simple risk-prediction tool that would

Table 1. Baseline Characteristics of Patients in the GRACE Model*

Development
Cohort
(n = 15 007)

Characteristics
Age, y
Mean (SD)
Median (IQR)
Men
Medical history
Coronary artery bypass graft
Diabetes mellitus
Hypertension
Myocardial infarction
Percutaneous coronary intervention
Hyperlipidemia
Prior or current smoking
Congestive heart failure
Prior medical therapy
Aspirin
Thienopyridines
ACE inhibitors
-Blockers
Calcium channel blockers
Oral nitrates
Digoxin
Diuretics
Statins
Signs and symptoms at presentation
Pulse, beats/min
Mean (SD)
Median (IQR)
Systolic blood pressure, mm Hg
Mean (SD)
Median (IQR)

Validation
Cohort
(n = 7638)

Vital Status
Unknown
(n = 5116)

65 (13)
65 (13)
66 (55.5-74.6)
66 (55.4-75.3)
9966 (66.8)
5061 (66.8)

65 (13)
66 (55.0-75.0)
3493 (67.9)

1997 (13.4)
3511 (23.5)
8683 (58.2)
4778 (32.0)
2283 (15.3)
6786 (45.6)
8611 (57.8)
1504 (10.1)

1005 (13.2)
1894 (24.9)
4574 (60.2)
2277 (30.0)
1392 (18.3)
3691 (48.7)
4437 (58.3)
729 (9.6)

570 (11.1)
1213 (23.5)
3115 (60.5)
1480 (29.0)
873 (17.0)
2330 (45.4)
2983 (57.8)
485 (9.4)

6496 (43.4)
622 (3.5)
3803 (25.6)
4603 (30.8)
3071 (20.8)

3196 (41.9)
523 (6.9)
2178 (28.7)
2577 (34.0)
1400 (18.6)

1900 (36.7)
283 (5.6)
1311 (25.6)
1519 (30.0)
946 (18.8)

3674 (24.6)
759 (5.2)
2634 (17.7)

1592 (21.0)
367 (4.9)
1479 (19.6)

1039 (20.3)
255 (5.1)
832 (16.2)

3362 (22.6)

2111 (27.9)

11 076 (21.0)

79 (20)
76 (65-89)

79 (20)
76 (65-89)

79 (20)
76 (65-90)

143 (29)
140 (122-160)

143 (29)
140 (123-160)

142 (29)
140 (120-160)

1.2 (0.8)
1.0 (0.9-1.2)

1.2 (0.9)
1.0 (0.9-1.2)

Initial serum creatinine level, mg/dL

Mean (SD)
1.2 (0.8)
Median (IQR)
1.0 (0.9-1.2)
Killip class
I
12 368 (84.2)
II
1863 (12.7)
III
268 (2.7)
IV
60 (0.4)
Cardiac arrest
179 (1.2)
Initial cardiac enzyme
4999 (33.6)
ST segment
Deviation
7873 (52.5)
Depression
4813 (32.1)

6416 (85.2)
885 (11.8)
200 (2.7)
32 (0.4)
93 (1.2)
3256 (44.0)

4406 (86.8)
517 (10.2)
115 (2.3)
36 (0.7)
52 (1.0)
2178 (42.8)

4055 (53.0)
2494 (32.7)

2879 (55.5)
1603 (31.0)

Abbreviations: ACE, angiotensin-converting enzyme; GRACE, Global Registry of Acute Coronary Events; IQR, interquartile range.
SI conversion factor: To convert creatinine to mol/L, multiply by 88.4.
*Data are No. (%) unless otherwise specified. Patients may have had more than 1 comorbidity or used more than 1
medication.
Value of the first serum creatinine or cardiac enzyme drawn following presentation to hospital for the acute event.
Degree of heart failure present on admission categorized by Killip class.

2728 JAMA, June 9, 2004Vol 291, No. 22 (Reprinted)

be applicable to all types of ACS,

would focus on an important clinical
end point of all-cause mortality, and
be developed in patients who are
similar to those encountered in routine clinical practice.
METHODS
The Global Registry of Acute Coronary
Events (GRACE) is a multinational cooperative effort involving 94 hospitals in
14 countries that has been designed to
reflect an unbiased, representative population of patients with ACS. Full details
of the GRACE methods have been previously published.11,12 For this analysis,
patients had to be at least 18 years old
and alive at the time of discharge, be admitted for ACS as a presumptive diagnosis (ie, have symptoms consistent with
acute myocardial ischemia), and have at
least 1 of the following: electrocardiographic changes consistent with ACS, serial increases in serum cardiac biomarkers, and/or documentation of coronary
artery disease. The qualifying ACS must
not have been precipitated by significant noncardiovascular comorbidity,
such as acute anemia or hyperthyroidism. At approximately 6 months after
hospital discharge, patients were followed up to ascertain vital status. At each
enrolling hospital, study investigators
worked with their ethics or institutional review board to obtain appropriate approval to participate.
To ensure enrollment of an unbiased population, the first 10 to 20 consecutive eligible patients were recruited from each site per month. Data
were collected by trained coordinators using a standardized case report
form. Demographic characteristics,
medical history, presenting symptoms, biochemical and electrocardiographic findings, treatment practices,
and a variety of hospital outcome data
were collected. Standardized definitions for all patient-related variables and
clinical diagnoses were used.11,12 At discharge, all cases were assigned to
STEMI, NSTEMI, or unstable angina
categories.11,12 Standardized definitions were used for selected hospital
complications and outcomes.11

2004 American Medical Association. All rights reserved.

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PREDICTION MODEL FOR ACUTE CORONARY SYNDROMES

Model Development

The primary end point was all-cause

mortality occurring within 6 months of
discharge from hospital. The model was
developed by using a multivariable Cox
proportional hazards regression backward elimination technique.13 The following variables were included in the
stepwise Cox proportional hazards regression: baseline characteristics, symptoms and signs at presentation, inhospital treatments and procedures, and
in-hospital complications. A backward
stepwise technique evaluated all potential univariate correlates (P.25) to create a multivariable model containing
variables with P.05. No imputation
was performed on the final model. Imputation was tested but did not influence the identification of multivariate
predictors or the discriminative power
of the model for predicting death.14 All
variables in the final model met the assumptions for proportional hazards.
The model accuracy was tested in several ways. First, we developed the model
in all patients with ACS enrolled in
GRACE between April 1, 1999, and
March 31, 2002. The c statistic was extended to evaluate the discrimination
of survival analytic techniques.15 We
checked for any nonlinear relationship between death and each variable
in the final model and found none. Selected testing was performed for interactions using the significant prognostic variables from the final model based
on interactions that have been reported from other published models.
Second, we tested the model in a validation cohort of consecutive patients
enrolled in GRACE between April 1,
2002, and December 31, 2003. Statistical analyses were performed using SAS
version 8.2 (SAS Institute Inc, Cary,
NC) and S-Plus version 3.4 (MathSoft
Inc, Seattle, Wash).
The overall follow-up rate in our development cohort was 87.5% for death.
A comparison of the patients with and
those patients without available follow-up data demonstrated no significant clinical differences in terms of
baseline characteristics, symptoms at
presentation, in-hospital treatments and

procedures, in-hospital outcomes, and

postdischarge outcomes.
Making the Model Usable

We developed a bedside prediction tool

that can be applied to either a pocket

card or a handheld device. Clinical prediction variables were given weighted

scores based on the models variable coefficients. The prediction tool considers the variables taken from the final
model assigning a point total to each

Table 2. In-Hospital Treatments and Outcomes of Patients in the GRACE Model*

Characteristics
Length of hospital stay, median (IQR), d
Patients who died
Patients discharged alive
In-hospital medical therapy and procedures
Catheterization in the absence of PCI
and CABG
PCI
CABG
Lytics
Aspirin
Thienopyridines
ACE inhibitors
-Blockers
Calcium channel blockers
Unfractionated heparin
Low-molecular-weight heparin
Warfarin
Glycoprotein IIb/IIIa
Digoxin
Diuretics
Statins
In-hospital complications
Congestive heart failure
Cardiogenic shock
Atrial fibrillation
Cardiac arrest
Sustained VT/VF
Atrioventricular block
Major bleeding
Renal insufficiency
Stroke
Recurrent ischemia
Medical therapy at hospital discharge
Aspirin
Thienopyridines
Warfarin
ACE inhibitors
-Blockers
Calcium channel blockers
Digoxin
Diuretics
Statins

Development
Cohort
(n = 15 007)

Validation
Cohort
(n = 7638)

8 (5-12)
6 (3-10)

6 (3-10)
6 (3-9)

2862 (19.3)

1456 (19.3)

1048 (20.3)

3945 (26.6)
719 (5.0)
2457 (16.5)

2563 (34.0)
355 (4.7)
1061 (14.1)

1651 (32.1)
193 (3.8)
714 (14.0)

14 023 (93.6)
4688 (31.8)
8380 (56.4)
12 019 (80.6)
426 (28.6)
7869 (53.1)
7371 (50.0)
965 (6.6)
2668 (18.0)
1269 (8.6)
4815 (32.4)
7347 (49.3)

7197 (94.4)
3930 (52.0)
4921 (64.8)
6414 (84.6)
1832 (24.4)
3500 (46.4)
4612 (60.8)
504 (6.8)
1932 (25.7)
573 (7.7)
2589 (34.3)
5061 (67.0)

4759 (92.0)
2287 (45.2)
3236 (63.2)
4274 (83.3)
1239 (24.6)
2417 (47.8)
3086 (60.5)
322 (6.5)
1138 (22.4)
352 (7.0)
1576 (31.4)
2216 (43.2)

902 (6.5)
192 (1.3)
1119 (7.5)
229 (1.5)
315 (2.1)
266 (1.8)
327 (2.2)

466 (6.6)
93 (1.2)
516 (6.8)
80 (1.1)
180 (2.4)
128 (1.7)
162 (2.2)

255 (5.3)
106 (2.1)
348 (6.8)
80 (1.6)
135 (2.6)
108 (2.1)
100 (2.0)

378 (2.5)
80 (0.5)
4265 (28.6)

206 (2.7)
336 (0.4)
1847 (24.4)

120 (2.4)
40 (0.8)
1065 (21.0)

12 158 (87.7)
3952 (29.0)
912 (6.7)
7107 (51.6)
9684 (70.2)
3259 (23.7)
862 (6.3)
3149 (22.9)
6963 (50.5)

6184 (90.2)
3198 (47.0)
462 (6.9)
4159 (60.8)
5263 (77.1)
1314 (19.4)
389 (5.9)
1659 (24.5)
4546 (66.7)

3998 (87.3)
1825 (40.6)
288 (6.6)
2716 (59.8)
3372 (74.3)
866 (19.3)
230 (5.2)
968 (21.5)
2624 (57.8)

Vital Status
Unknown
(n = 5116)
NA
NA

Abbreviations: ACE, angiotensin-converting enzyme; CABG, coronary artery bypass graft; GRACE, Global Registry of
Acute Coronary Events; IQR, interquartile range; NA, not available; PCI, percutaneous coronary intervention; VT/VF,
ventricular tachycardia/ventricular fibrillation.
Data
are No. (%) unless otherwise specified. Patients may have had more than 1 in-hospital procedure or complica*
tion and used more than 1 medication at hospital discharge.

2004 American Medical Association. All rights reserved.

(Reprinted) JAMA, June 9, 2004Vol 291, No. 22

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2729

PREDICTION MODEL FOR ACUTE CORONARY SYNDROMES

Table 3. Multivariate Predictors for the 6-Month Postdischarge Mortality Model

Hazard Ratio (95% Confidence Interval)

228.6

Development Cohort
(n = 15 007)
1.8 (1.64-1.91)

History of myocardial infarction

History of congestive heart failure

22.0
66.5

1.5 (1.26-1.75)
2.2 (1.79-2.59)

1.2 (0.88-1.50)
2.0 (1.50-2.70)

1.4 (1.20-1.59)
2.1 (1.80-2.47)

Pulse per 30/min increase

Systolic blood pressure per 20-mm Hg decrease
Initial serum creatinine level per 1-mg/dL increase*
Initial cardiac enzyme elevation*
ST-segment depression

28.8
21.5
28.1
33.3
19.2

1.3 (1.16-1.43)
1.1 (1.08-1.20)
1.2 (1.11-1.24)
1.6 (1.39-1.89)
1.4 (1.22-1.69)

1.4 (1.20-1.66)
1.0 (0.92-1.19)
1.2 (1.10-1.30)
1.5 (1.20-1.99)
1.6 (1.25-2.05)

1.3 (1.23-1.47)
1.1 (1.06-1.17)
1.2 (1.12-1.23)
1.5 (1.33-1.79)
1.5 (1.29-1.69)

No in-hospital PCI
c Statistic

14.8

1.6 (1.24-1.96)
0.81

1.5 (1.11-2.11)
0.75

1.9 (1.30-1.88)
0.77

Predictors
Age per 10-year increase

Validation Cohort
(n = 7638)
1.7 (1.48-1.86)

All Patients With ACS

(n = 22 645)
1.7 (1.63-1.84)

Abbreviations: ACS, acute coronary syndrome; PCI, percutaneous coronary intervention.

*Value of the first serum creatinine or cardiac enzyme drawn following presentation to hospital for the acute event.

Table 4. Model Performance in the STEMI, NSTEMI, and Unstable Angina Groups

Figure 1. Comparison of Predicted vs

Observed Mortality Rate for the Validation
Cohort

c Statistic

Development cohort
Validation cohort
All patients with ACS

16

Observed Mortality Rate, %

14
12

STEMI
0.71
0.76
0.80

NSTEMI
0.78
0.78
0.78

Unstable Angina
0.76
0.70
0.75

Abbreviations: ACS, acute coronary syndrome; NSTEMI, nonST-segment elevation myocardial infarction; STEMI,
ST-segment elevation myocardial infarction.

10
8
6
4
2
0
0

10

12

14

16

Predicted Mortality Rate, %

Each data marker represents a decile of risk.

variable, which allows a total point

score for each patient to be calculated.
This then is applied to a reference plot
nomogram, which shows the corresponding risk of death. Alternatively,
the risk of death could be calculated using a handheld device. The clinical application can be found at http://www
.outcomes-umassmed.org/grace.
RESULTS
Baseline characteristics, in-hospital
treatments, and outcomes of the 15007
patients used to develop the model (development cohort), 7638 patients used
to test the model (validation cohort),
and 5116 patients for whom 6-month

vital status was unknown are shown in

TABLE 1 and TABLE 2. The mean age
was 65 years and 67% of the cohort
were men. Prior or current smoking and
hypertension were present as risk factors in more than half of the patients.
Approximately 45% of patients had a
diagnosis of hyperlipidemia and less
than 25% had diabetes mellitus.
The 6-month mortality risk was similar in the development (4.8%, n=717)
and validation cohorts (4.7%, n=331).
Nine multivariate predictors of mortality were identified (TABLE 3). The
model calibrations were retained when
testing the model in an independent
validation cohort (Table 3 and
FIGURE 1). The model performed well
in all forms of ACS with a c statistic of
at least 0.70 (TABLE 4).
FIGURE 2 illustrates a method to estimate a patients risk depending on the
total score obtained by summing the individual scores for each of the 9 variables in the model. A similar nomogram can be programmed into a
handheld device to make the risk cal-

2730 JAMA, June 9, 2004Vol 291, No. 22 (Reprinted)

culation automatic once the individual variables have been entered.

COMMENT
We have developed and validated a
simple bedside prediction tool that can
be used to estimate a patients postdischarge risk of 6-month mortality in all
forms of ACS, regardless of their initial electrocardiogram or biomarker results. By using the power of the GRACE
registry (25000 patients studied) and
focusing on the clinically relevant and
wholly unbiased end point of allcause mortality, we believe that clinicians may find this tool usable and reliable as they attempt to make key
diagnostic and treatment decisions
among patients hospitalized with ACS.
Previous risk tools have been proposed in estimating in-hospital risk after admission for ACS,1,4,6-8 including
risk models developed from large clinical trials or registry data by the Thrombolysis in Myocardial Infarction (TIMI)
clinical trials group.4,9 These models are
robust in predicting risk for specific end

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PREDICTION MODEL FOR ACUTE CORONARY SYNDROMES

Figure 2. GRACE Prediction Score Card and Nomogram for All-Cause Mortality From Discharge to 6 Months

Risk Calculator for 6-Month Postdischarge Mortality After Hospitalization for Acute Coronary Syndrome
Record the points for each variable at the bottom left and sum the points to calculate the total risk score. Find the total score on
the x-axis of the nomogram plot. The corresponding probability on the y-axis is the estimated probability of all-cause mortality
from hospital discharge to 6 months.

Findings at Initial
Hospital Presentation

Medical History

1 Age in Years

Points

29

3039

4 Resting Heart Rate,

beats/min

Findings
During Hospitalization
7 Initial Serum
Creatinine, mg/dL

Points

Points

49.9

00.39

18

5069.9

0.40.79

36

7089.9

0.81.19

6069

55

90109.9

14

1.21.59

7079

73

110149.9

23

1.61.99

91

150199.9

35

23.99

15

200

43

20

4049
5059

8089
90

100

2 History of Congestive
Heart Failure

24

3 History of
Myocardial Infarction

5 Systolic Blood Pressure,

mm Hg

12

79.9

24

8099.9

22

100119.9

18

120139.9

14

140159.9

10

160199.9

200

ST-Segment Depression

Points
0.50

0.45

15

9 No In-Hospital
Percutaneous
Coronary Invervention

14

1
11

0.40

0.35
Probability

4
5
6
7

0.30
0.25
0.20
0.15

0.10

0.05

(Sum of Points)

0
70

Mortality Risk

8 Elevated Cardiac Enzymes

Predicted All-Cause Mortality From Hospital Discharge to 6 Months

Total Risk Score

90

110

130

150

170

190

210

(From Plot)
Total Risk Score

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2731

PREDICTION MODEL FOR ACUTE CORONARY SYNDROMES

points and in the population in which

they have been studied. However, comparison between our methods and those
of the TIMI group elucidate the issue
of using prediction models in practice. For example, many ACS trials, including the TIMI trial, have used a combined end point that includes recurrent
coronary ischemia with a secondary end
point of ischemia requiring coronary revascularization. This particular end
point is potentially troublesome because it is influenced by local practice
style in which the availability of a catheterization laboratory may have more
to do with a decision to revascularize
than with patient characteristics.16,17 It
may also lead to inaccuracies in overall prediction. For instance, prior coronary artery bypass graft surgery predicts an increased risk of death after
percutaneous coronary intervention but
a decreased likelihood of surgical coronary revascularization in patients undergoing coronary angioplasty.18 This
is because prior coronary artery bypass graft surgery is associated with a
worse complication rate after reoperative coronary artery bypass graft surgery, so surgeons may try to avoid it
where possible. In ACS, studies suggest that at the extremes of older age
or serum creatinine clearance, interventionalists reduce their use of percutaneous coronary intervention for
fear of complications, while at the same
time the risk of death steadily increases.19 Finally, it is not clear that revascularization is an event that should
be avoided. Given the benefits of an
early invasive strategy, revascularization may be considered a good event,
and in our analysis was a predictor of
improved survival at 6-months postdischarge.
Another limitation of prior ACS prediction models relates to the arbitrary
separation into STEMI and nonSTsegment elevation ACS populations. Because few models incorporate the entire spectrum of patients with ACS,
physicians wishing to apply these models in routine practice need to be aware
of multiple risk scores for different types
of patients with ACS. In the GRACE

model, we were able to demonstrate

that diagnostic prediction for inhospital mortality is similar whether the
ST-segment deviation is elevation or depression. 14 In this analysis, we extended that observation to show that
one can robustly predict 6-month mortality, regardless of whether the patient presents with STEMI, NSTEMI, or
unstable angina. The overall c statistic
is high (0.81) compared with other risk
models for combined end points such
as the TIMI risk model (0.65).9
How generalizable are prediction
tools? They are as generalizable as the
population from which they are derived. In this way, we believe that the
GRACE model is unique. In so far as
we have studied consecutive patients,
observed in care at 94 hospitals, representing 14 countries, and have used
a population-based enrollment wherever possible, the GRACE registry
model may well be closer to realworld practice than previous studies
limited to clinical trial populations or
single-region registries. As such, we believe that clinicians will find greater
confidence in its applicability in their
practices. Because it has been validated on patients enrolled in 2002 and
2003, clinicians can also feel confident that it is current.
GRACE is the largest multinational
registry study to include the entire spectrum of patients with ACS. It is designed to be representative of regional
communities and uses standardized criteria for defining ACS and hospital outcomes and quality control and audit
measures. Given the overall number of
deaths in the development (n=717) and
validation (n=331) cohorts, one has increased confidence of the robustness of
the model.
Risk-prediction tools are developed in
populations, not individuals. Although
the risk-prediction tools may inform
practitioners regarding the estimated
likelihood of complications in a patient, each individual patient is unique
and subject to many influences not measured or ascertained in clinical practice. Local practice referral patterns or
practice style may influence average risks

2732 JAMA, June 9, 2004Vol 291, No. 22 (Reprinted)

of patients being cared for by an individual clinician. To the extent that

GRACE studies patients cared for all
over the world by hundreds of clinicians, it has an excellent chance to adjust for this variation to create a riskprediction instrument that is robust for
most situations. However, like individual patients, each practice has its set
of unmeasured variation that may influence risks, such as socioeconomic status, which was not considered in the current model. The model is applicable to
patients hospitalized with ACS and discharged alive, not patients being observed in an emergency department.
In summary, our GRACE 6-month
postdischarge prediction model is a
simple robust tool for predicting death
in patients with ACS and has very good
discriminative ability. We believe that
clinicians will find it simple to use and
applicable to clinical practice.
Author Contributions: Dr Eagle had full access to all
of the data in the study and takes responsibility for
the integrity of the data and the accuracy of the data
analysis.
Study concept and design: Eagle, Dabbous, Goldberg,
Van de Werf, Goodman, Granger, Steg, Gore, Budaj,
Avezum, Flather, Fox.
Acquisition of data: Eagle, Lim, Van de Werf,
Goodman, Granger, Steg, Gore, Budaj, Avezum, Fox.
Analysis and interpretation of data: Eagle, Lim,
Dabbous, Pieper, Granger, Fox.
Drafting of the manuscript: Eagle, Lim, Dabbous, Fox.
Critical revision of the manuscript for important intellectual content: Eagle, Lim, Dabbous, Pieper,
Goldberg, Van de Werf, Goodman, Granger, Steg,
Gore, Budaj, Avezum, Flather, Fox.
Statistical expertise: Eagle, Dabbous, Pieper, Granger.
Administrative, technical, or material support: Eagle,
Granger, Gore.
Study supervision: Eagle, Goldberg, Van de Werf,
Goodman, Granger, Steg, Gore, Budaj, Avezum,
Flather, Fox.
The Complete List of the GRACE Investigators can
be found at http://www.outcomes-umassmed.org
/grace.
Funding/Support: The GRACE study is supported by
an unrestricted educational grant from Aventis Pharma
to the Center for Outcomes Research, University of
Massachusetts Medical School.
Role of the Sponsor: Aventis Pharma had no involvement in the collection, analysis, and interpretation of
data; in the writing of the manuscript; and in the decision to submit the paper for publication. The design, conduct, and interpretation of GRACE are undertaken by an independent steering committee.
Additional Information: Further information about the
GRACE project can be found at http://www
.outcomes-umassmed.org/grace.
Acknowledgment: We thank and express our gratitude to the physicians and nurses participating in
GRACE. Sophie Rushton-Mellor, PhD, provided editorial support for the manuscript and was funded by
Aventis Pharma through the GRACE registry. We also
thank Fred Anderson, PhD, the principal investigator
of the GRACE registry.

2004 American Medical Association. All rights reserved.

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PREDICTION MODEL FOR ACUTE CORONARY SYNDROMES

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An education isnt how much you have committed to

memory, or even how much you know. Its being able
to differentiate between what you do know and what
you dont.
Anatole France (1844-1924)

2004 American Medical Association. All rights reserved.

(Reprinted) JAMA, June 9, 2004Vol 291, No. 22

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2733