European Heart Journal (2005) 26, 18–26

doi:10.1093/eurheartj/ehi002

Clinical research

Mortality rates in patients with ST-elevation vs.

non-ST-elevation acute myocardial infarction:
observations from an unselected cohort
Christian Juhl Terkelsen1*, Jens Flensted Lassen1, Bjarne Linde Nørgaard1,
Jens Christian Gerdes1,2, Tage Jensen2, Liv Bjørn-Hansen Gøtzsche2,

Downloaded from http://eurheartj.oxfordjournals.org/ by guest on November 15, 2015

Torsten Toftegaard Nielsen1, and Henning Rud Andersen1
1
Department of Cardiology, Skejby University Hospital, DK-8200 Aarhus N, Denmark
2
Department of Internal Medicine, Randers County Hospital, DK-8900 Randers, Denmark
Received 3 June 2004; revised 10 October 2004; accepted 14 October 2004; online publish-ahead-of-print 23 November 2004

See page 1 for the editorial comment on this article (doi:10.1093/eurheartj/ehi062)

KEYWORDS Aims Acute myocardial infarction (AMI) is categorized, according to the presenting
Myocardial infarction; electrocardiogram, into non-ST-elevation myocardial infarction (non-STEMI), ST-
Prognosis; elevation myocardial infarction (STEMI), or bundle branch block myocardial infarction
Cohort study; (BBBMI). Data on the prognostic significance of these categories mainly originate
Selection bias;
from voluntary based registries or large-scale clinical trials and may be hampered
Information bias
by selection and information bias. The aim of this historical cohort study was to evalu-
ate the prognostic significance of different categories of AMI in an unselected cohort.
Methods and results From 1 November 1999 to 31 October 2001, patient records were
reviewed from all admissions to hospitals serving a study region with 139 000 inhabi-
tants. An Endpoint Committee determined whether patients fulfilled the European
Society of Cardiology criteria of AMI. A total of 654 patients with AMI were identified.
The proportion having non-STEMI, STEMI, and BBBMI was 54, 39 and 6%, and the associ-
ated 1 year mortality was 31, 21, and 55%, respectively (log rank 54, P , 0.001). The
more favourable outcome observed in patients with STEMI remained significant
according to multivariable analysis (P ¼ 0.044).
Conclusion In an unselected cohort of patients admitted with AMI, the mortality was
considerably higher than expected from voluntary-based registries and large-scale
clinical trials. The most favourable outcome is observed in patients with STEMI.

Introduction Treatment is tailored according to these categories.

Acute myocardial infarction (AMI) is categorized,
according to the presenting electrocardiogram (ECG),
into non-ST-elevation myocardial infarction (non-
STEMI), ST-elevation myocardial infarction (STEMI), or
bundle branch block myocardial infarction (BBBMI).1
* Corresponding author. Tel: þ45 89496234; fax: þ45 89496009.
E-mail address: christian_juhl_terkelsen@hotmail.com
Thus, patients with non-STEMI should be stabilized
medically and scheduled for an early (within days)
interventional strategy.2,3 Patients with STEMI or BBBMI
should be treated acutely with thrombolysis or primary
percutanous coronary intervention (primary PCI), if
admitted within 12 h of onset of symptoms.1,4–6
Hitherto, data on prognosis according to the different
categories of AMI mainly originated from registries based
on voluntarily reported cases,7–9 or from large-scale

European Heart Journal vol. 26 no. 1 & The European Society of Cardiology 2004; all rights reserved.
Mortality in ST-elevation acute myocardial infarction
randomized controlled trials with numerous inclusion
and exclusion criteria. These registries and trials may
be hampered by selection and information bias.
The purpose of this study was to evaluate the prog-
nostic significance of the different categories of AMI in
an unselected cohort of patients.
Methods
Population
The study region encompassed 139 000 inhabitants. A local
hospital (Randers County Hospital) and an interventional
centre with primary PCI facilities (Skejby University Hospital)
served the study region. The interventional centre was located
35 km from the local hospital. From 1 November 1999 to 31
October 2001, all hospital admissions were registered to ident-
ify: (i) all patients who were admitted as emergencies to the cor-
onary care unit at the local hospital (any hospital diagnosis); (ii)
all patients assigned a hospital diagnosis of AMI at other medical
departments at the local hospital; and/or (iii) patients trans-
ferred acutely to the interventional centre for primary PCI.
Patients transferred from other departments due to peri-
operative myocardial infarction, or from other hospitals in
which they initially had been treated for AMI, were excluded.
Patient records and laboratory data were reviewed. ECGs for
the first 48 h of admission, and an ECG from a previous admission
(if present) were collected for the following patients:
(i) patients with a rise in coronary biochemical markers {creati-
nine kinase (CK) level
150 U/L, creatinine kinase myocardial
band þ brain band [CK(M)B þ BB] level
12 U/L, creatinine
kinase myocardial band (CKMB) level
10 mg/L or troponin-T
(tnT) level
0.10 mg/L} within 24 h of admission; (ii) patients
treated with thrombolysis or primary PCI; (iii) patients assigned
a hospital diagnosis of AMI at discharge; and (iv) patients
assigned a pre-hospital or in-hospital working diagnosis of
STEMI or BBBMI. To identify patients who fulfilled the European
Society of Cardiology (ESC) and American College of Cardiology
(ACC) criteria of AMI10 within 24 h of admission, an Endpoint
Committee (C.J.T., J.F.L., B.L.N. and J.C.G.) reviewed all the
collected material. If agreement was reached between two
members of the Endpoint Committee then the diagnosis of AMI
was accepted, otherwise additional members were consulted
and a majority vote accepted. In addition to the ESC/ACC
criteria of AMI, the Endpoint Committee accepted a diagnosis
of AMI in patients dying prior to blood sampling or before a poss-
ible rise in coronary biochemical markers could be detected,
if typical symptoms and ECG signs of AMI were present on
admission. A diagnosis of aborted MI was accepted in patients
with normal levels of coronary biochemical markers, if the
patient presented with typical symptoms of AMI and ST-elevation
that disappeared after early initiation of reperfusion therapy.
Based on the presenting ECGs, the Endpoint Committee cate-
gorized the type of AMI: STEMI was present if ST-segment
elevation occurred in two adjacent leads (
0.1 mV in lead I,
II, III, aVF, aVL, V4–V6 or
0.2 mV in leads V1–V3). If new (or
presumably new) bundle branch block (BBB) was present
(absence of BBB on prior admission or no prior ECG) the AMI
was categorized as BBBMI. The remaining patients, including
those with pacemaker-rhythm and pre-existing BBB, were
categorized as having non-STEMI. If signs of AMI were not
present on admission but appeared within 24 h of admission,
the subtype of AMI was categorized according to the assumed
index ECG.
19
Data collection
The following variables were registered from the patient
files: age, sex, history of hypertension, diabetes, congestive
heart failure (CHF), angina pectoris (AP), previous myocardial
infarction (MI), coronary artery bypass grafting (CABG), or PCI,
smoking (within 1 year), pre-hospital contact with a primary
care physician, ambulance transportation or not to hospital,
on-scene delay (time from ambulance arrival on-scene to
scene departure), transport delay (time from ambulance call
to arrival at hospital), pre-hospital delay (time from onset of
symptoms to arrival at hospital), medical treatment on admis-
sion, heart rhythm and rate in the admission ECG, type of reper-
fusion therapy (thrombolysis or primary PCI), hyperlipidaemia
(treatment with lipid-lowering drugs on admission or at dis-
charge, total cholesterol .5.0, or low-density lipoprotein
.3.0), peak level of coronary biochemical markers and plasma
creatinine within 72 h of admission, PCI or CABG performed
during hospitalization or scheduled at discharge, ejection frac-
tion (by echocardiography or ventriculography), and medication
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at discharge. The 1 November 2003 available data from the first
coronary angiography performed following the index myocardial
infarction (number and location of diseased vessels with stenosis
.50%) were collected from a central administrative angiography
registry, and mortality data were registered using the Civil
Registration system registry (CPR registry) in Denmark. Median
follow-up time was 2.4 years (inter-quartile range: 0.6–3.1
years).
Statistics
Categorical variables are expressed as % (n ) and continuous
variables as medians (inter-quartile range). The Fisher Exact
test and Kruskal–Wallis test were used for comparison of
categorical and continuous variables as appropriate. Unadjusted
survival data are plotted as Kaplan–Meier curves, and compari-
son between groups was performed using log rank statistics.
Cox regression analysis was used to evaluate the prognostic
significance of the following variables concerning mortality at
follow-up: age, sex, history of hypertension, diabetes, CHF,
AP, or MI, smoking (within 1 year), pre-hospital contact
with primary care physician, ambulance transportation or not
to hospital, on-scene delay, transport delay, pre-hospital delay,
heart rhythm and rate in the admission ECG, ejection fraction,
hyperlipidaemia, peak level of coronary biochemical markers
and plasma creatinine within 72 h of admission, medical treat-
ment on admission, and coronary angiography data (number
and location of diseased vessels with stenosis .50%). Hazard
ratios (95% CI) are presented. The proportional hazard assump-
tion was checked for each categorical variable through visual
inspection and by the method described by Grambsch and Ther-
neau,11 using the Schoenfeld residuals. For continuous variables,
the linearity assumption was checked graphically for all vari-
ables using the Martingale residuals. Analysis of interaction
between covariates was made for the categories of AMI vs. cor-
onary biochemical marker rise. Variables with P , 0.20 in the
univariable Cox regression analysis were included in the multi-
variable Cox regression model. However, the following variables
were not considered for inclusion in the multivariable model
since data were only available in a minority of patients: CK,
CK(M)B þ BB, and coronary angiography data. The number of
parameters included in the multivariable model was held
below one-tenth of the number of events. Variable selection
was performed in the multivariable Cox regression analysis as
a stepwise backward elimination method, each time excluding
the one variable with the highest P value according to Wald
20
statistics. The final model (Model I) included variables with
P , 0.05. The importance of the categories of AMI in the final
model was tested using a Likelihood Ratio test (LR test) compar-
ing the full model with a sub-model not including the categories
of AMI. The final model was refitted in the whole population by
replacing missing values with their conditional means (continu-
ous variables) or conditional probabilities (categorical variables)
(Model II). These imputed values were obtained as predictions
from a regression model or logistic model using all non-missing
covariates in each subject.12,13 A third multivariable model
(Model III) was presented implementing a fourth category of
AMI (non-STEMI with pre-existing BBB). Statistical significance
level was P , 0.05 (two-sided test). The software packages
SPSS 10.0 and STATA 8.0 were used for statistical analyses.
Results
In the 2 year study period, hospital records and labora-
tory data were reviewed from 4815 patient admissions.
The Endpoint Committee identified 727 cases of AMI in
654 patients, and categorized 57.6% (n ¼ 419) as non-
STEMI, 36.5% (n ¼ 265) as STEMI, and 5.9% (n ¼ 43) as
BBBMI. In 11 cases the Endpoint Committee confirmed
a hospital diagnosis of AMI despite the lack of coronary
biochemical marker rise: 1 with aborted MI, whereas
the remaining 10 presented with classical symptoms
and ECG manifestations of AMI, however, death occurred
before blood sampling or a rise in biochemical markers
could be detected (four with non-STEMI, four with
STEMI, and two with BBBMI). Including patients first
registered at admission only, 54.1% (n ¼ 354) of AMIs
were categorized as non-STEMI, 39.4% (n ¼ 258) as
STEMI, and 6.4% (n ¼ 42) as BBBMI.
When compared with patients with non-STEMI and
BBBMI, patients with STEMI were younger, more often
male, less often with a history of diabetes, CHF, or
previous MI, with a shorter pre-hospital delay and lower
heart rate on admission, more often with sinus rhythm
on admission and hyperlipidaemia, and presenting a
higher peak coronary biochemical marker rise and lower
peak creatinine level (Table 1). Patients with non-STEMI
had a higher ejection fraction compared with patients
with STEMI and BBBMI (Table 1). No difference in the
number and location of diseased coronary vessels could
be demonstrated between patients according to the
different categories of AMI (Table 1).
Patients with STEMI were less often treated with
angiotensin-converting enzyme inhibitors, angiotensin-
2-antagonists, beta-blockers, aspirin or diuretics on
admission, and diuretics at discharge, and more often
with beta-blockers, clopidogrel and lipid-lowering drugs
at discharge, when compared with the rest of the study
group (Table 2).
Among patients with STEMI, 79% (n ¼ 205) were admit-
ted within 12 h of symptom onset, 70% (n ¼ 143) of the
latter were treated acutely with reperfusion therapy
(Table 3). Median (IQR) age among patients with STEMI
receiving reperfusion therapy was 65 (56–73) years, and
median (IQR) pre-hospital delay 2.3 (1.1–4.5) h. Among
patients with non-STEMI, 48% (n ¼ 170) were scheduled
for an early interventional strategy (Table 3). The latter
C.J. Terkelsen et al.
patients had a median (IQR) age of 67 (58–76) years
and presented with a median (IQR) pre-hospital delay
of 4.0 (1.8–7.6) h.
The unadjusted 1 year mortality was 28.1% in the com-
plete cohort, being 30.5%, 20.5%, and 54.8% in patients
with non-STEMI, STEMI, and BBBMI, respectively (log
rank 54, P , 0.001) (Table 3) (Figure 1). Lower 1 year
mortality was observed in patients admitted within 12 h
of symptom onset (n ¼ 433) compared with patients
admitted later after the onset of symptoms (n ¼ 221)
(22.9% vs. 38.5%, log rank 30, P , 0.001). Among patients
with non-STEMI, lower 1 year mortality was observed in
patients scheduled for an early interventional strategy
(n ¼ 170) compared with patients treated conservatively
(n ¼ 184) (10.0% vs. 49.5%, log rank 95, P , 0.001).
Among patients with STEMI admitted within 12 h of
symptom onset, lower 1 year mortality was observed in
those treated with reperfusion therapy (n ¼ 143) com-
pared with those treated conservatively (n ¼ 62) (10.5%
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vs. 33.9%, log rank 18, P , 0.001). Among patients with
non-STEMI, 10.5% (n ¼ 37) had pre-existing BBB. These
patients had a higher 1 year mortality compared with
non-STEMI without pre-existing BBB (n ¼ 317) (50.0% vs.
28.4%, log rank 10, P ¼ 0.015).
Variables predicting mortality at follow-up according
to univariable Cox regression analyses are presented
in Table 4. TnT did not provide prognostic information
in the complete study cohort, and high levels of CK,
CK(M)B þ BB as well as CKMB were associated with an
improved clinical outcome (Table 4). Sub-analyses
revealed statistical interaction between the catego-
ries of AMI and biochemical marker rise, thus, the
latter associations were not statistically significant
within the different categories of AMI. Within the group
of non-STEMI patients high levels of tnT were associated
with poor prognosis [hazard ratio ¼ RR ¼ 1.124
(1.037–1.219), P ¼ 0.005].
The following risk variables provided independent
prognostic information in multivariable analysis: age,
peak creatinine level within 72 h of admission, history
of CHF, pre-hospital delay, ejection fraction, and cat-
egory of AMI (Model I) (Table 5). When refitting the
model in the whole population, based on imputed
missing values, pre-hospital delay did not remain signi-
ficant (Model II) (Table 5). When including a fourth
category of AMI, patients with non-STEMI and pre-existing
BBB presented an intermediate hazard compared with
non-STEMI-patients without pre-existing BBB and patients
with BBBMI (Model III) (Table 5).
Discussion
The aim of the present study was to evaluate the prog-
nostic significance of different categories of AMI in an
unselected cohort of patients. In these terms it is con-
sidered as a ‘confirmative prognostic factor study’.14
We believe that this study is unique in that a total
cohort of patients admitted with AMI from the chosen
study region was identified, a diagnosis of AMI was only
accepted if confirmed by an Endpoint Committee and
Mortality in ST-elevation acute myocardial infarction 21

Table 1 Baseline characteristics, in-hospital and post-discharge data according to different categories of acute myocardial
infarction

Non-ST-elevation n ST-elevation n Bundle branch n P

myocardial myocardial block myocardial
infarction infarction infarction

Age (years) 75 (65–81) 354 69 (58–77) 258 80 (74–85) 42 ,0.001

Male sex 58% (205) 354 67% (172) 258 52% (22) 42 0.043
Medical history of
Hypertension 25% (89) 353 24% (63) 258 31% (13) 42 0.64
Diabetes 23% (80) 354 14% (35) 258 40% (17) 42 ,0.001
Heart failure 14% (50) 354 2% (4) 257 17% (7) 42 ,0.001
Angina pectoris 50% (175) 353 41% (105) 257 38% (16) 42 0.063
Myocardial infarction 26% (92) 353 11% (29) 257 21% (9) 42 ,0.001
CABG 3% (12) 353 1% (3) 257 0% (0) 42 0.17
PCI 4% (13) 354 3% (7) 257 5% (2) 42 0.65
Smoking (within 1 year) 68% (202) 296 74% (167) 225 60% (18) 30 0.14
Pre-hospital data
Contact with primary care physician 73% (260) 354 67% (174) 258 74% (31) 42 0.26

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Transported by ambulance 85% (288) 339 84% (213) 253 88% (35) 40 0.91
On-scene delay (min) 12 (8–15) 190 12 (8–16) 158 13 (8–17) 17 0.89
Transport delay (min) 36 (25–49) 266 35 (25–46) 196 30 (21–51) 32 0.29
Pre-hospital delay (h) 4.8 (2.0–12) 267 3.3 (1.5–8.5) 240 4.5 (2.1–15) 36 0.025
ECG data on admission
Non-sinus rhythm 27% (95) 346 12% (28) 243 36% (15) 42 ,0.001
Heart rate (per min) 91 (70–113) 344 77 (62–93) 243 111 (87–129) 42 ,0.001
Ejection fraction 55 (38–60) 267 49 (36–60) 204 35 (25–45) 27 ,0.001
Hyperlipidaemia 59% (209) 352 69% (177) 256 60% (24) 40 0.041
Laboratory data
Peak CK (U/L) 293 (154–564) 101 1353 (566–2840) 94 245 (157–804) 16 ,0.001
Peak CK(M)B þ BB (U/L) 20 (14–39) 101 76 (31–176) 93 18 (13–26) 15 ,0.001
Peak CKMB (mg/L) 19 (8–53) 297 152 (29–435) 226 14 (6–58) 30 ,0.001
Peak troponin-T (mg/L) 0.5 (0.2–1.4) 299 3.1 (1.0–6.8) 226 0.5 (0.2–1.4) 31 ,0.001
Peak creatinine (mmol/L) 103 (83–141) 350 92 (82–111) 252 133 (97–182) 41 ,0.001
CAG-data availablea 55% (198) 354 50% (130) 258 31% (13) 42 0.008
Number of diseased vessels 2 (1–3) 198 2 (1–3) 130 3 (1–3) 13 0.85
RCA stenosis 60% (119) 197 61% (79) 130 62% (8) 13 1.00
CX stenosis 66% (129) 197 55% (72) 130 62% (8) 13 0.17
LAD stenosis 65% (129) 197 73% (95) 130 77% (10) 13 0.31
Main stem stenosis 13% (25) 196 11% (14) 130 15% (2) 13 0.72

Categorical data are presented as % (n) and continuous data as median values (inter-quartile range).
a
At time of follow-up. CAG: coronary angiography. CABG: coronary artery by pass grafting. CK: creatinine kinase. CK(M)B þ BB: creatinine kinase
myocardial band þ brain band. CKMB: creatinine kinase myocardial band. CX: circumflex artery. LAD: left anterior descending artery. n: number of
valid cases. On-scene delay: time from ambulance arrival at the scene of event to ambulance departure. PCI: percutanous coronary intervention.
Pre-hospital delay: time from onset of symptoms to arrival at hospital. RCA: right coronary artery. Transport delay: time from ambulance call to
arrival at hospital.

fulfilling the ESC/ACC criteria of AMI (with minor modi-
fications), and the three categories of AMI (non-STEMI,
STEMI, and BBBMI) were accepted as independent
entities, thus STEMI and BBBMI were not combined.
Thereby, potential selection and information bias was
limited.
The present study was performed during the same
period as the Global Registry of Acute Coronary Events
(GRACE), the Euro Heart Survey of Acute Coronary
Syndromes (EHS-ACS), and the third National Registry of
Myocardial Infarction (NRMI-3).8,9,15,16 Nonetheless, the
proportion of patients with STEMI was 52% in GRACE15
and 63% in EHS-ACS,8 hence considerably higher than
the 39% observed in the present study. Moreover, the
in-hospital mortality of 5% observed in both GRACE and
EHS-ACS,8,15 as well as the in-hospital mortality of 9%
observed in NRMI-3,9 were lower than the 14% observed
in the present study. These discrepancies may be
explained by the fact that all three registries relied on
voluntarily reported cases. Thus, it may be that large
myocardial infarctions (instantly detectable on admis-
sion) were more likely to be registered, resulting in a
higher proportion of patients with STEMI being included.
Moreover, no methods ensured that consecutive patients
were included in these registries. In GRACE and EHS-ACS,
some patients were required to give consent to join the
registries, a strategy potentially leading to exclusion of
high-risk patients who could not receive information or
give written consent.8,15 Patients dying within 24 h of
admission tended to be excluded from GRACE, which
also in part explains the low mortality observed.17,18
In EHS-ACS a high proportion of patients were registered
22 C.J. Terkelsen et al.

Table 2 Medication on admission and at discharge according to different categories of acute myocardial infarction

Non-ST-elevation ST-elevation Bundle branch block P

myocardial infarction myocardial infarction myocardial infarction

Medication on admission n ¼ 354 n ¼ 257 n ¼ 42

ACE/AT2 22% (77) 13% (33) 26% (11) 0.006
Beta-blocker 24% (84) 12% (32) 29% (12) 0.001
Aspirin 50% (176) 26% (68) 52% (22) ,0.001
Diuretics 49% (174) 22% (56) 62% (26) ,0.001
Lipid-lowering 10% (35) 5% (14) 7% (3) 0.14
Medication at discharge n ¼ 307 n ¼ 230 n ¼ 27
ACE/AT2 27% (82) 35% (80) 48% (13) 0.02
Beta-blocker 69% (211) 87% (199) 70% (19) ,0.001
Aspirin 93% (284) 97% (223) 93% (25) 0.055
Clopidogrel 17% (53) 23% (53) 4% (1) 0.024
Diuretics 63% (194) 41% (95) 89% (24) ,0.001
Lipid-lowering 35% (108) 51% (118) 30% (8) ,0.001

Categorical data presented as % (n).

ACE: angiotensin converting enzyme inhibitor. AT2: angiotensin-II-antagonist. n: number of patients.

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Table 3 Unadjusted mortality according to different categories of acute myocardial infarction

Number of In-hospital One-year mortality

patients (n ) mortality (95% CI) (95% CI)

Acute myocardial infarction 654 13.6% (11.0–16.2) 28.1% (24.9–31.8)

Non-ST-elevation myocardial infarction 354 13.3% (9.7–16.8) 30.5% (26.0–35.6)
Admitted 12 h after symptom onset 199 9.0% (5.0–13.1) 23.6% (18.3–30.2)
Early interventional strategya 170 1.8% (0–3.8) 10.0% (6.3–15.6)
ST-elevation myocardial infarction 258 10.9% (7.0–14.7) 20.5% (16.1–26.0)
Admitted 12 h after symptom onset 205 9.8% (5.7–13.9) 17.6% (13.0–23.5)
Acute reperfusion therapyb 143 4.9% (1.3–8.5) 10.5% (6.5–16.8)
Bundle branch block myocardial infarction 42 33.3% (18.5–48.2) 54.8% (40.6–70.1)
Admitted 12 h after symptom onset 29 34.5% (16.1–52.9) 55.2% (38.4–73.5)
Acute reperfusion therapy 3 33.3% (0–100) 33.3% (5.5–94.6)
a
Coronary angiography performed during index hospitalization or scheduled at discharge.
b
Thrombolytic therapy or primary percutaneous coronary intervention.

at academic centres with revascularization facilities,
hence potentially resulting in selection bias and contri-
buting to the lower mortality observed.8 In GRACE,
patients with BBBMI were categorized as STEMI, thus
any improved outcome in patients with STEMI as com-
pared to non-STEMI may have been underestimated.19
Finally, in none of the three registries was an Endpoint
Committee consulted to reach agreement upon diagnosis,
thus potentially leading to information bias.8,9 The
mortality observed in the present study was also
considerably higher than expected from numerous
large-scale clinical trials, in which 1 year mortality con-
sistently is reported as ,10%.5,6,20–24 Possible expla-
nations are that numerous inclusion and exclusion
criteria are implemented in the latter trials, patients
included in the latter trials are admitted in a favourable
condition enabling them to give written informed
consent, and the proportion of patients receiving
optimal reperfusion therapy is considerably higher in
the latter trials when compared with the real world
scenario.7 Moreover, an inherent selection bias is
always present in large-scale clinical trials as evident
from the fact that higher mortality is observed among
those eligible for inclusion but not included in the
trials.25,26 The latter is consistent with the findings in
the present study, in which the subgroup of patients
with STEMI treated with reperfusion therapy had signifi-
cantly lower mortality when compared with remaining
STEMI patients admitted within 12 h of symptom onset.
The observation in the present study that patients with
non-STEMI have higher unadjusted mortality compared
with patients with STEMI has previously been explained
by the fact that the former patients have more pro-
nounced co-morbidity as well as more frequent multi-
vessel disease.16 Indeed, we found several risk factors
to be more frequent among non-STEMI patients.
However, there were no differences in the number of
diseased vessels, and ejection fraction was higher, and
coronary biochemical marker release lower, among
patients with non-STEMI compared with patients with
Mortality in ST-elevation acute myocardial infarction
Figure 1 Unadjusted Kaplan–Meier survival curves for different cat-
egories of acute myocardial infarction. STEMI: ST-elevation myocardial
infarction. Non-STEMI: non-ST-elevation myocardial infarction. BBBMI:
myocardial infarction with newly developed bundle branch block.
STEMI. Moreover, the more favourable outcome in
patients with STEMI remained significant according to
multivariable Cox regression analyses. It may also be
speculated that a part of the more favourable outcome
in patients with STEMI is influenced by different treat-
ment strategies. In the FRISC-II and TACTICS trials a
benefit from an early interventional treatment strategy
was documented in patients with non-STEMI.27
However, the present study was performed in a period
in which the early interventional strategy was not fully
implemented. Nonetheless, one-half of patients with
non-STEMI were scheduled for an early interventional
strategy, comparable to the findings in GRACE.7,19
The availability in the present study of new bio-
chemical markers such as the troponins in the majority
of patients, combined with the Endpoint Committee’s
implementation of the redefined ESC/ACC criteria of
AMI, may also contribute to the lower number of patients
categorized as STEMI when compared with GRACE and
EHS-ACS, as well as the higher mortality observed
in patients with non-STEMI compared with patients
with STEMI. Previous findings indicate that changing the
AMI diagnostic strategy, from the older WHO to the
ESC/ACC criteria introduced in 2000, leads to the identi-
fication of nearly 50% additional patients.28 The majority
of these patients are categorized as having non-STEMI,
and among these higher mortality is observed when com-
pared with patients identified by the WHO criteria.28
The mortality among patients with BBBMI was extre-
mely high in the present study consistent with previous
findings.29,30 Likewise, patients with BBBMI were found
to have more co-morbid illness than those with non-
STEMI or STEMI.29 The proportion of patients with
BBBMI was lower than the 13% observed in the Second
National Registry of Myocardial Infarction (NRMI-2).29
In the latter registry, however, all patients admitted
with AMI and BBB were categorized as BBBMI. In the
present study, patients with AMI who had pre-existing
BBB (identified on previous admission) were categorized
as non-STEMI. This may in part explain the higher
in-hospital mortality observed among BBBMI patients
23
when compared with the 23% observed in NRMI-2. The
use of reperfusion therapy in patients with BBBMI
admitted within 12 h of symptom onset was comparable
to the 8% observed in NRMI-2.29 The hesitation to initiate
reperfusion therapy in patients with BBBMI probably
relies on the fact that the diagnosis is difficult to estab-
lish in the acute phase, and it may be speculated
whether referral of all chest pain patients with docu-
mented or presumably new BBB (normal previous ECG
or no previous ECG) to an interventional centre is the
optimal diagnostic strategy. Whether patients with AMI
and pre-existing BBB should be categorized as having
non-STEMI may be a matter of controversy. Certainly,
an intermediate hazard was observed in these patients
compared with remaining patients with non-STEMI and
patients with BBBMI. However, we believe that the
implemented categories are the ones used in real life
when tailoring therapy. Furthermore, implementation
of a fourth category of AMI (non-STEMI with pre-existing
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BBB) in the multivariable analysis did not seem to
change the hazard in patients having non-STEMI without
pre-existing BBB. The broader confidence limits observed
probably reflect the limited power of the present
study, thus indicating the need for larger confirmative
prognostic studies in the future.
Rather unexpectedly we found that the tnT level did
not provide independent prognostic information in the
complete cohort of patients with AMI, but within the
group of patients having non-STEMI. This is explained by
interaction between variables, i.e. mortality was lower,
but the tnT rise higher, in patients with STEMI compared
with patients with non-STEMI. In patients with STEMI, the
high tnT levels may in part be a mere result of tnT release
in relation to reperfusion therapy. Thus, the prognostic
information achieved from biochemical markers probably
should be interpreted according to the category of AMI.
The higher patient age and more prolonged pre-
hospital delay observed in the present study compared
with GRACE and EHS-ACS is also expected to reflect the
real-life scenario. Thus, among patients with STEMI
treated with reperfusion therapy and patients with non-
STEMI scheduled for an early interventional strategy,
the median age was comparable to previous observations
in large-scale European trials.20,27 This is consistent
with findings by Jha and colleagues31 reporting a con-
siderably higher age among non-trial patients compared
with trial patients. In patients with STEMI treated with
reperfusion therapy the median pre-hospital delay
was even shorter in the present study compared with
EHS-ACS.8
Study limitations
As in any study, potential residual confounding may have
been present, i.e. inclusion of other baseline variables
could have delivered additional prognostic information.
Certainly, Killip class was considered for inclusion in
the Cox regression analysis. However, this parameter
was not routinely registered in the patient records.
Furthermore, Killip class may be considered as a conse-
quence of the category of AMI, i.e. a higher Killip class
24 C.J. Terkelsen et al.

Table 4 Prognostic significance of selected variables concerning mortality at follow-up according to univariable Cox regression
analyses

Median (IQR) Valid casesa P Hazard ratio ¼ RR

or % (n) (95% CI)

Age (years) 73 (62–80) 654 ,0.001 1.071 (1.058–1.084)

Male sex 61% (399) 654 0.020 0.749 (0.588–0.954)
Medical history of
Hypertension 25% (165) 653 0.70 1.055 (0.801–1.390)
Diabetes 20% (132) 654 0.004 1.516 (1.152–1.994)
Heart failure 9% (61) 653 ,0.001 2.986 (2.180–4.090)
Angina pectoris 45% (296) 652 0.51 0.922 (0.724–1.175)
Myocardial infarction 20% (130) 652 0.25 1.187 (0.890–1.583)
Smoking (within 1 year) 70% (387) 551 0.029 0.719 (0.537–0.961)
Pre-hospital data
Contact with primary care physician 71% (465) 654 0.023 1.375 (1.038–1.821)
Transported by ambulance 85% (536) 632 ,0.001 1.946 (1.277–2.966)
On-scene delay (min) 12 (8–16) 365 0.71 0.994 (0.965–1.025)
Transport delay (min) 35 (25–47) 494 0.20 0.999 (0.998–1.000)

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Pre-hospital delay (h) 3.8 (1.8–10) 543 0.004 1.004 (1.002–1.007)
ECG data on admission
Non-sinus rhythm 22% (138) 631 ,0.001 1.975 (1.518–2.569)
Heart rate (per min) 85 (66–107) 629 ,0.001 1.008 (1.004–1.011)
Ejection fraction 50 (35–60) 498 ,0.001 0.960 (0.950–0.971)
Hyperlipidaemia 63% (410) 648 ,0.001 0.425 (0.333–0.542)
Laboratory data
Peak CK (U) 520 (191–1500) 211 0.009 1.000 (1.000–1.000)
Peak CK(M)B þ BB (U) 32 (16–89) 209 ,0.001 0.995 (0.991–0.999)
Peak CKMB (mg/L) 33 (11–154) 553 ,0.001 0.999 (0.998–1.000)
Peak troponin-T (mg/L) 0.97 (0.32–3.3) 556 0.22 0.984 (0.958–1.011)
Peak creatinine (mmol/L) 99 (83–130) 643 ,0.001 1.004 (1.003–1.005)
Category of AMI (reference: STEMI) 654 ,0.001
Non-STEMI 354 1.953 (1.472–2.590)
BBBMI 42 4.307 (2.827–6.563)
Medication on admission
ACE/AT2 19% (121) 653 0.002 1.587 (1.197–2.103)
Beta-blocker 20% (128) 653 0.65 1.072 (0.793–1.448)
Aspirin 41% (266) 653 ,0.001 1.549 (1.217–1.971)
Diuretics 39% (256) 653 ,0.001 2.605 (2.040–3.326)
Lipid-lowering agents 8% (52) 653 0.051 0.617 (0.367–1.039)
Coronary angiography datab
Number of diseased vessels 2 (1–3) 341 0.002 1.418 (1.128–1.784)
Right coronary artery stenosis 61% (206) 340 0.072 1.516 (0.953–2.411)
Circumflex artery stenosis 61% (209) 340 0.025 1.700 (1.051–2.750)
Left anterior descending artery stenosis 69% (234) 340 0.009 1.974 (1.143–3.401)
Main stem stenosis 12% (41) 339 0.80 1.086 (0.576–2.050)
a
Without missing values.
b
Information available at time of follow-up.
ACE: angiotensin converting enzyme inhibitor. AMI: acute myocardial infarction. AT2: angiotensin-II-antagonist. BBBMI: bundle branch block
myocardial infarction. CK: creatinine kinase. CKMB: creatinine kinase myocardial band. CK(M)B þ BB: creatinine kinase myocardial band þ brain
band. IQR: inter-quartile range. Non-STEMI: non-ST-elevation myocardial infarction. On-scene delay: time from ambulance arrival at the scene of
event to ambulance departure. Pre-hospital delay: time from onset of symptoms to arrival at hospital. STEMI: ST-elevation myocardial infarction.
Transport delay: time from ambulance call to arrival at hospital.

is expected in patients with STEMI because of a greater
deterioration in left ventricular function.32,33 In this
setting inclusion of Killip class would result in over-
adjustment and thus underestimate the real prognostic
information achieved from the AMI categorization.
Selection bias was limited. In Denmark, all AMI patients
are admitted to public hospitals, and only two hospitals
served the study region, hence all hospital-admitted
patients should have been identified. However, a small
number of patients initially admitted to the emergency
care unit may have died immediately following admission
before being assigned to a ward. Any such patients would
be missed in the present study, but they would be few in
number and, if anything, result in an underestimation of
mortality. Potential information bias was also limited
because the AMI diagnosis was only accepted if confirmed
Mortality in ST-elevation acute myocardial infarction 25

Table 5 Variables retained in the final multivariable Cox regression models

P Hazard ratio ¼ RR (95% CI)

Model I, n ¼ 421
Age (years) ,0.001 1.062 (1.042–1.083)
Creatinine level (mmol/L) ,0.001 1.003 (1.002–1.004)
History of heart failure ,0.001 2.448 (1.527–3.925)
Pre-hospital delay (h) ,0.001 1.006 (1.003–1.010)
Ejection fraction 0.003 0.978 (0.964–0.992)
Category of AMI (reference: STEMI) 0.044
Non-STEMI 1.612 (1.036–2.506)
BBBMI 2.071 (1.062–4.038)
Model II, n ¼ 654 (model based on imputed missing values)
Age (years) ,0.001 1.061 (1.047–1.075)
Creatinine level (mmol/L) ,0.001 1.002 (1.001–1.003)
History of heart failure 0.001 1.801 (1.264–2.567)
Ejection fraction 0.003 0.983 (0.972–0.994)
Category of AMI (reference: STEMI) 0.018
Non-STEMI 1.337 (0.988–1.810)

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BBBMI 1.858 (1.200–2.880)

Model III, n ¼ 654 (model based on imputed missing values)

Age (years) ,0.001 1.061 (1.047–1.075)
Creatinine level (mmol/L) ,0.001 1.002 (1.001–1.003)
History of heart failure 0.002 1.775 (1.241–2.549)
Ejection fraction 0.003 0.983 (0.972–0.994)
Category of AMI (reference: STEMI) 0.038
Non-STEMI without pre-existing BBB 1.321 (0.973–1.792)
Non-STEMI with pre-existing BBB 1.534 (0.917–2.564)
BBBMI 1.866 (1.204–2.892)

Likelihood ratio test comparing the full model with a sub-model not including the categories of AMI.
BBB: bundle branch block. BBBMI: bundle branch block myocardial infarction. Non-STEMI: non-ST-elevation myocardial infarction. Non-STEMI with
pre-existing BBB: non-STEMI with BBB in previous ECG. Non-STEMI without pre-existing BBB: non-STEMI without BBB in previous ECG. Pre-hospital
delay: time from onset of symptoms to admission. STEMI: ST-elevation myocardial infarction.

by an Endpoint Committee. Concerning the external Conclusion

study validity, one should always be cautious in extrapo-
lating the results to other regions, and the present find-
ings are at most representative for hospital-admitted
patients with AMI since the study did not include non-
admitted patients.
In an unselected cohort of patients admitted with AMI,
the mortality is considerably higher than expected from
voluntary-based registries and large-scale clinical trials,
and the most favourable outcome is observed in patients
with STEMI.

Perspectives
The high mortality observed in the present study com-
pared with consistently lower mortality reported in
voluntary-based registries and large-scale clinical trials
calls for care when extrapolating results and out-
comes of voluntary registries and clinical trials to the
real world clinical scenario. In planning future trials,
one should implement this knowledge and consider limit-
ing the number of inclusion and exclusion criteria
to achieve higher event rates and improve the external
study validity. Assuming that the strategy of acute
reperfusion therapy and adjunctive medication con-
tributes to the more favourable outcome observed in
patients with STEMI, further clarification of the role of
catheter-based and adjunctive pharmacological inter-
ventions in patients with BBBMI and non-STEMI are
needed.
Acknowledgements
Professor Werner Vach, Department of Statistics, Uni-
versity of Southern Denmark is thanked for statistical
support. The study was supported by the Danish Heart
Foundation (Grant 01-2-3-28A-22925 and 02-2-3-58-
22026), the Laerdal Foundation of Acute Medicine,
Karl G Andersons Foundation, The A.P. Møller Foundation
for the Advancement of Medical Science, Elin Holms
Foundation and Kirsten Anthonius’ Foundation.
References
1. Van de Werf F, Ardissino D, Betriu A, Cokkinos DV, Falk E, Fox KA,
Julian D, Lengyel M, Neumann FJ, Ruzyllo W, Thygesen C, Underwood SR,
Vahanian A, Verheugt FW, Wijns W. Management of acute myocardial
26
infarction in patients presenting with ST-segment elevation.
Eur Heart J 2003;24:28–66.
2. Braunwald E, Antman EM, Beasley JW, Califf RM, Cheitlin MD,
Hochman JS, Jones RH, Kereiakes D, Kupersmith J, Levin TN,
Pepine CJ, Schaeffer JW, Smith EE 3rd, Steward DE, Theroux P,
Gibbons RJ, Alpert JS, Faxon DP, Fuster V, Gregoratos G, Hiratzka LF,
Jacobs AK, Smith SC Jr. ACC/AHA guideline update for the manage-
ment of patients with unstable angina and non-ST-segment elevation
myocardial infarction—2002: summary article: a report of the
American College of Cardiology/American Heart Association Task
Force on Practice Guidelines (Committee on the Management of
Patients with Unstable Angina). Circulation 2002;106:1893–1900.
3. Braunwald E. Application of current guidelines to the management
of unstable angina and non-ST-elevation myocardial infarction.
Circulation 2003;108:28111–28137.
4. Boersma E, Maas AC, Deckers JW, Simoons ML. Early thrombolytic
treatment in acute myocardial infarction: reappraisal of the golden
hour. Lancet 1996;348:771–775.
5. Fibrinolytic Therapy Trialists’ (FTT) Collaborative Group. Indications
for fibrinolytic therapy in suspected acute myocardial infarction:
collaborative overview of early mortality and morbidity results
from all randomised trials of more than 1000 patients. Lancet
1994;343:311–322.
6. Keeley EC, Boura JA, Grines CL. Primary angioplasty versus intra-
venous thrombolytic therapy for acute myocardial infarction: a quan-
titative review of 23 randomised trials. Lancet 2003;361:13–20.
7. Eagle KA, Goodman SG, Avezum A, Budaj A, Sullivan CM, Lopez-
Sendon J. Practice variation and missed opportunities for reperfusion
in ST-segment-elevation myocardial infarction: findings from the
Global Registry of Acute Coronary Events (GRACE). Lancet
2002;359:373–377.
8. Hasdai D, Behar S, Wallentin L, Danchin N, Gitt AK, Boersma E,
Fioretti PM, Simoons ML, Battler A. A prospective survey of the
characteristics, treatments and outcomes of patients with acute
coronary syndromes in Europe and the Mediterranean basin. The
Euro Heart Survey of Acute Coronary Syndromes (Euro Heart Survey
ACS). Eur Heart J 2002;23:1190–1201.
9. Rogers WJ, Canto JG, Lambrew CT, Tiefenbrunn AJ, Kinkaid B, Shoultz DA,
Frederick PD, Every N. Temporal trends in the treatment of over 1.5
million patients with myocardial infarction in the US from 1990
through 1999: the National Registry of Myocardial Infarction 1, 2
and 3. J Am Coll Cardiol 2000;36:2056–2063.
10. The Joint European Society of Cardiology/American College of
Cardiology Committee. Myocardial infarction redefined—a consensus
document of The Joint European Society of Cardiology/American
College of Cardiology Committee for the Redifinition of Myocardial
Infarction. Eur Heart J 2000;21:1502–1513.
11. Grambsch PM, Therneau TM. Proportional hazards tests and diagnos-
tics based on weighted residuals. Biometrika 1994;81:515–526.
12. Schemper M, Smith TL. Efficient evaluation of treatment effects in
the presence of missing covariate values. Stat Med 1990;9:777–784.
13. Schemper M, Heinze G. Revisited for prognostic factor studies.
Stat Med 1997;16:73–80.
14. Simon R, Altman DG. Statistical aspects of prognostic factor studies
in oncology. Br J Cancer 1994;69:979–985.
15. Goldberg RJ, Currie K, White K, Brieger D, Steg PG, Goodman SG,
Dabbous O, Fox KA, Gore JM. Six-month outcomes in a multinational
registry of patients hospitalized with an acute coronary syndrome
(The Global Registry of Acute Coronary Events [GRACE]). Am J
Cardiol 2004;93:288–293.
16. Goldberg RJ, Steg PG, Sadiq I, Granger CB, Jackson EA, Budaj A,
Brieger D, Avezum A, Goodman S. Extent of, and factors associated
with, delay to hospital presentation in patients with acute coronary
disease (the GRACE registry). Am J Cardiol 2002;89:791–796.
17. Granger CB, Goldberg RJ, Dabbous O, Pieper KS, Eagle KA, Cannon CP,
Van de Werf F, Avezum A, Goodman SG, Flather MD, Fox KAA, for the
Global Registry of Acute Registry of Acute Coronary Events
Investigators. Predictors of hospital mortality in the global registry
of acute coronary events. Arch Intern Med 2003;163:2345–2353.
18. Armstrong PW. Coronary reperfusion: numerators searching for
denominators. Lancet 2002;359:371–372.
C.J. Terkelsen et al.
19. Steg PG, Goldberg RJ, Gore JM, Fox KA, Eagle KA, Flather MD, Sadiq I,
Kasper R, Rushton-Mellor SK, Anderson FA. Baseline characteristics,
management practices, and in-hospital outcomes of patients
hospitalized with acute coronary syndromes in the Global Registry
of Acute Coronary Events (GRACE). Am J Cardiol 2002;90:358–363.
20. Andersen HR, Nielsen TT, Rasmussen K, Thuesen L, Kelbaek H,
Thayssen P, Abildgaard U, Pedersen F, Madsen JK, Grande P, Villadsen
AB, Krusell LR, Haghfelt T, Lomholt P, Husted SE, Vigholt E,
Kjaergard HK, Mortensen LS. A Comparison of coronary angioplasty
with fibrinolytic therapy in acute myocardial infarction. N Engl J
Med 2003;349:733–742.
21. The GUSTO V Investigators. Reperfusion therapy for acute myocardial
infarction with fibrinolytic therapy or combination reduced fibrino-
lytic therapy and platelet glycoprotein IIb/IIIa inhibition: the
GUSTO V randomised trial. Lancet 2001;357:1905–1914.
22. Assessment of the Safety and Efficacy of a New Thrombolytic
(ASSENT-2) Investigators. Single-bolus tenecteplase compared with
front-loaded alteplase in acute myocardial infarction: the ASSENT-2
double blind randomised trial. Lancet 1999;354:716–722.
23. Sinnaeve P, Alexander J, Belmans A, Bogaerts K, Langer A, Diaz R,
Ardissino D, Vahanian A, Pehrsson K, Armstrong P, Van de Werf F.
One-year follow-up of the ASSENT-2 trial: a double-blind, randomized
comparison of single-bolus tenecteplase and front-loaded alteplase
Downloaded from http://eurheartj.oxfordjournals.org/ by guest on November 15, 2015
in 16,949 patients with ST-elevation acute myocardial infarction.
Am Heart J 2003;146:27–32.
24. Lincoff AM, Califf RM, Van de WF, Willerson JT, White HD, Armstrong PW,
Guetta V, Gibler WB, Hochman JS, Bode C, Vahanian A, Steg PG,
Ardissino D, Savonitto S, Bar F, Sadowski Z, Betriu A, Booth JE,
Wolski K, Waller M, Topol EJ. Mortality at 1 year with combination
platelet glycoprotein IIb/IIIa inhibition and reduced-dose fibrinolytic
therapy vs conventional fibrinolytic therapy for acute myocardial
infarction: GUSTO V randomized trial. JAMA 2002;288:2130–2135.
25. Brown N, Melville M, Gray D, Young T, Skene AM, Wilcox RG, Hampton JR.
Relevance of clinical trial results in myocardial infarction to medical
practice: comparison of four year outcome in participants of a throm-
bolytic trial, patients receiving routine thrombolysis, and those
deemed ineligible for thrombolysis. Heart 1999;81:598–602.
26. Bahit MC, Cannon CP, Antman EM, Murphy SA, Gibson CM, McCabe CH,
Braunwald E. Direct comparison of characteristics, treatment, and
outcomes of patients enrolled versus patients not enrolled in a
clinical trial at centers participating in the TIMI 9 Trial and TIMI 9
Registry. Am Heart J 2003;145:109–117.
27. Wallentin L, Lagerqvist B, Husted S, Kontny F, Stahle E, Swahn E.
Outcome at 1 year after an invasive compared with a non-invasive
strategy in unstable coronary-artery disease: the FRISC II invasive
randomised trial. FRISC II investigators. Fast revascularisation
during instability in coronary artery disease. Lancet 2000;356:9–16.
28. Pell JP, Simpson E, Rodger JC, Finlayson A, Clark D, Anderson J, Pell AC.
Impact of changing diagnostic criteria on incidence, management,
and outcome of acute myocardial infarction: retrospective cohort
study. Br Med J 2003;326:134–135.
29. Go AS, Barron HV, Rundle AC, Ornato JP, Avins AL. Bundle-branch
block and in-hospital mortality in acute myocardial infarction. Ann
Intern Med 1998;129:690–697.
30. Sgarbossa EB, Pinski SL, Topol EJ, Califf RM, Barbagelata A, Goodman SG,
Gates KB, Granger CB, Miller DP, Underwood DA, Wagner GS. Acute
myocardial infarction and complete bundle branch block at hospital
admission: clinical characteristics and outcome in the thrombolytic
era. J Am Coll Cardiol 1998;31:105–110.
31. Jha P, Deboer D, Sykora K, Naylor CD. Characteristics and
mortality outcomes of thrombolysis trial participants and nonparti-
cipants: a population-based comparison. J Am Coll Cardiol 1996;
27:1335–1342.
32. Holmes DR, Jr, Berger PB, Hochman JS, Granger CB, Thompson TD,
Califf RM, Vahanian A, Bates ER, Topol EJ. Cardiogenic shock
in patients with acute ischemic syndromes with and without
ST-segment elevation. Circulation 1999;100:2067–2073.
33. Neskovic A, Otasevic P, Bojic M, Popovic AD. Association of Killip
class on admission and left ventricular dilatation after myocardial
infarction: a closer look into an old clinical classification. Am Heart
J 1999;137:361–367.