Temporal decline in the prognostic impact of a recurrent acute
myocardial infarction 1985 to 2002
P Buch, S Rasmussen, G H Gislason, J N Rasmussen, L Køber, N Gadsbøll, S Stender, M Madsen,
C Torp-Pedersen, S Z Abildstrom
............................................................... ............................................................... .....
See end of article for
Dr Pernille Buch, Department
of Cardiovascular Medicine,
Hospital, Bispebjerg Bakke
23, Building 40 2400
Copenhagen NV, Denmark;
Accepted 21 July 2006
Published Online First
29 August 2006
Heart 2007;93:210–215. doi: 10.1136/hrt.2006.092213
Objective: To investigate trends in case-fatality and prognostic impact from recurrent acute myocardial
infarction (re-AMI) during 1985–2002.
Design: Retrospective cohort study using nationwide administrative data from Denmark.
Settings: National registries on hospital admissions and causes of death were linked to identify patients with
first AMI, re-AMI and subsequent prognosis.
Patients: Patients >30 years old with a discharge diagnosis of AMI during 1985–2002 were tracked for first
hospital admission for re-AMI 1 year after discharge.
Main outcome measures: One-year case-fatality.
Results: 166 472 patients were identified with a first AMI; 14 123 developed re-AMI. One-year crude case-
fatality from first AMI/re-AMI was 39% versus 43% in 1985–1989 and 25% versus 29% in 2000–2002,
respectively. In 1985–89, 35 795 patients survived to discharge (71%); of these 2.5% experienced
reinfarction within 30 days (early reinfarction) and an additional 9.0% reinfarction within days 31–365 (late
re-AMI). Re-AMI carried a poor prognosis in 1985–1989 compared to no re-AMI with age- and sex-adjusted
relative risk of 1-year case-fatality of 7.5 (95% CI: 6.9 to 8.5) from early re-AMI and 11.7 (95% CI: 11.0 to
12.4) from late re-AMI. In 2000–2002, 23 552 patients (86%) survived to discharge; 4.4% had early re-AMI
and 6.6% late re-AMI. Adjusted relative risk of 1-year case-fatality had declined to 2.1 (95% CI: 1.9 to 2.5)
from early re-AMI and 5.6 (95% CI: 5.1 to 6.2) from late re-AMI compared to patients without reinfarction.
Conclusion: Prognosis after AMI has improved substantially during the latest two decades and extends to
patients with re-AMI.
risk of subsequent death.1–4During the last two decades the
mortality from an AMI has decreased considerably, influenced
by multiple factors including improvement in treatment and
changes in lifestyle.5 6Whether the prognosis of a recurrent
AMI has changed in a similar manner is largely unknown. A
decrease in mortality from recurrent AMI would be anticipated
because of the widespread use of secondary prevention and
intensified treatment of patients with established coronary
artery disease. Further, the increasing use of more sensitive
biomarkers and new definitions of an AMI may have changed
the prognostic impact of a recurrent AMI in an unknown
Information about the prognostic implication of a recurrent
infarction is important for many reasons. Not only is it
important in patient management and counselling, but
recurrent AMI is also considered a valid endpoint in clinical
trials. Several major new treatment strategies have been
introduced based on studies where the clinical benefit was
reduction of recurrent AMI.8–10Due to the substantial decline in
mortality from a first AMI, it is necessary to know the extent to
which this applies to a recurrent AMI. Therefore, we have
performed a nationwide register-based study to follow the
trends in mortality after a recurrent AMI from 1985 to 2002.
recurrent acute myocardial infarction (AMI) is generally
considered a serious event in survivors of myocardial
infarction, and many studies have demonstrated a high
This study was based on administrative data from the Danish
National Patient Registry, which covers all admissions to Danish
hospitals since 1978.11Briefly, the registry contains basic
information about the patient (age and gender), dates of
admission and discharge, and all diagnoses during hospital stay.
Data for the registry are processed at each hospital discharge and
include a primary discharge diagnosis coded according to the
International Classification of Diseases (ICD) by the discharging
physician. We identified patients aged 30 years or older with a
first admission for anAMIduringtheperiod 1 January1985 to31
December 2002. The population was subsequently tracked for
first hospitalisation for recurrent AMI occurring within the first
year after discharge. The rationale for the follow-up duration of
1 year was a clustering of events during the first 6 months and
far fewer events after this. Information on survival status was
obtained from the Civil Registration System which registers all
deaths in Denmark within 2 weeks. One-year mortality status
was available for all patients.
Definitions of a first AMI and a recurrent AMI
A first AMI was defined as first hospital admission recorded in
the National Patient Registry on condition that no previous
AMI had been recorded in the preceding 7 years. This arbitrary
limit was selected because this was the furthest back we were
able to trace patients admitted in 1985, and this length of time
was applied to all patients in our cohort. To identify the
hospitalisations for a first AMI or a first recurrent AMI we used
the ICD-8 code 410 (from 1978 to 1994) and ICD-10 code I21–
22 (from 1994 to 2002). Only primary discharge diagnoses were
used. A recurrent AMI was defined as any new admission for
AMI within 1 year after discharge following the initial AMI,
provided that the interval between the day of admission for first
AMI and the day of admission for the recurrent AMI was at
Abbreviations: AMI, acute myocardial infarction; ICD, International
Classification of Diseases; PCI, percutaneous coronary intervention
least 5 days to avoid misclassification. If a patient experienced
more than one reinfarction, only the first was used in analyses.
Validation of the diagnosis of a first and a recurrent
The diagnosis of AMI in the National Hospital Registry has been
Determinants of Cardiovascular Disease (MONICA) Registry
where standardised WHO definitions of AMI are used. The
positive predictive value was 93.6% and sensitivity was 78% for
definite or possible AMI (93% for definite AMI).12To study the
validity of a recurrent AMI diagnosis, we randomly validated 48
diagnoses in two hospitals by a review of the hospital records.
To be classified as a definite recurrent AMI, two out of three
criteria had to be fulfilled: clinical symptoms together with
either significant enzyme/troponin rise or ST-segment changes.
We only chose recent cases between 2000 and 2001 so that we
could obtain a complete sample of the records. Of these 48
patients, 40 (83%) were retrospectively found to have a definite
recurrent AMI and an additional three had possible reinfarc-
tion, leaving 90% with a diagnosis of definite or possible
reinfarction. In patients where the diagnosis of a recurrent AMI
could not be confirmed, two had angina, one had congestive
heart failure and two were incorrectly coded as AMI during
The calendar years from 1985 to 2002 were categorised into four
pre-selected periods: 1985–1989, 1990–1994, 1995–1999 and
2000–2002. We chose a shorter interval for the latest period to
according to international guidelines. The remaining periods were
divided into equal intervals of 4 years. Due to the frequent use of
early reinfarction as the endpoint in recent trials, we investigated
trends in mortality from both early and late recurring AMI. A
recurrent AMI was categorised as early if it occurred within the
first 30 days of the initial AMI (counting from the day of
admission) or late if it occurred from day 31 to 365.
Trends in continuous baseline variables were tested by one-
way variance analysis and categorical variables by x2test. One-
year case-fatality plots, stratified by period, were generated
separately for the whole AMI population, that is, all patients
with first time AMI, and for patients with a recurrent AMI by
means of the Kaplan–Meier method and compared by the log-
rank test. Lifetime was calculated as time from admission for
either first AMI or recurrent AMI.
A Cox proportional hazard model was used to estimate
hazard rates of case-fatality from first AMI or recurrent AMI
during periods with the earliest period (1985–1989) as
reference. The model was adjusted for sex and age (10-year
age groups). To compare risk of death within the first year
between patients with a recurrent AMI and patients without a
recurrent AMI, an extended Cox model was used, in which
recurrent AMI served as a time-dependent variable. In brief,
this model switches a patient with recurrent AMI from the
initial value of 0 (at the time of the index admission) to a value
of 1 at the time of the reinfarction. In this way, the period that
patients had survived to the moment of the recurrent AMI was
calculated as a survival period without exposure. Patients
entered the model from the discharge date of their first AMI
(delayed entry) to adjust for any differences in length of
hospital stay during periods. Thus, only hospital survivors of
the initial admission were included in these analyses.
Hazard ratios were reported as relative risks with 95%
confidence intervals (CIs), obtained from the likelihood ratio
test. Calculations were made with Statistical Analysis System
software, version 8.2 (SAS Institute, Cary, NC).
According to Danish law, retrospective register studies do not
require ethical approval. The study was approved by the Danish
Data Protection Agency.
A total of 168 013 patients had a first AMI between 1985 and
2002. Of these, 1518 patients with an in-hospital stay exceeding
60 days were excluded and 23 patients were excluded due to
missing values. Thus, 166 472 patients (99.1%) were included
in the analyses. During the 19-year follow-up, 14 123 (8.4%)
patients developed a recurrent AMI within the first year after
admission for the index AMI.
Demographics of study population and patients with a
Patients with recurrent AMI were slightly older than patients
with first AMI, and age increased by 3 years during the study
period. Additionally, more patients with recurrent AMI were
male (table 1). Median length of hospital stay decreased by
3 days over the years for patients with first AMI and by 5 days
for patients with recurrent AMI. The 1-year incidence of
recurrent AMI did not change significantly with time. However,
the incidence of early recurrent AMI increased with periods,
while the opposite was true for late recurrent AMI (p,0.001).
One-year case-fatality after admission from first AMI
and first recurrent AMI
The cumulative 1-year case-fatality following a first AMI
decreased from 39% in 1985–1989 to 25% in 2000–2002 (fig 1).
The corresponding 30-day case-fatality declined from 30% to
15%. Most of this decline was due to a decrease in in-hospital
case-fatality from 29% in 1985–1989 to 14% in 2000–2002 (data
not shown). A similar decline in case-fatality was seen in
patients with a recurrent AMI. One-year case-fatality was 43%
in 1985–1989 and 29% in 2000–2002 (fig 2); 30-day case-
fatality decreased from 28% to 14% in the same periods. The
age- and sex-adjusted relative risk of death after first AMI was
0.50 (95% CI: 0.49 to 0.51) in 2000–2002 with years 1985–1989
as reference; the corresponding relative risk after recurrent AMI
was 0.48 (95% CI: 0.44 to 0.53).
One-year case-fatality after early and late recurrent
Early occurring recurrent AMIs had a more pronounced
reduction in case-fatality compared to later reinfarctions with
crude 1-year case-fatality of 46% in 1985–1989, 33% in 1990–
1994, 28% in 1995–1999 and 19% in 2000–2002. For late
reinfarctions, 1-year case-fatality was 42% in 1985–1989, 37%
in 1990–1994, 32% in 1995–1999 and 35% in 2000–2002. After
age- and sex-adjustment, the relative risk of case-fatality after
early recurrent AMI was 0.33 (95% CI: 0.28 to 0.39) in 2000–
2002 compared to 1985–1989; for late recurrent AMI, the
corresponding relative risk was 0.58 (95% CI: 0.53 to 0.64). No
differences were found in age- and sex-distribution between
early and late recurrent AMI.
The prognostic impact of recurrent AMI in hospital
survivors of first AMI
Table 2 shows the relative risk of 1-year case-fatality associated
with recurrent AMI during 1985–2002. The reference group is
hospital survivors without reinfarction who survived to the
time of reinfarction in the compared group. A recurrent AMI
carried a poor prognosis in 1985–1989, but prognosis improved
over time. For early recurrent AMIs there was a 72% decrease in
relative risk of death; for late recurrent AMIs the risk was
reduced by approximately 50%. Note that the exact values of
Decline in mortality from recurrent AMI 1985 to 2002 211
relative risks between groups of recurrent AMIs (early or late)
cannot be compared; only the relative reduction in risk is
comparable. This is due to the reduced risk of mortality in the
reference group with elapsed time from the initial infarction.
Patients without a recurrent AMI from 31 to 365 days would be
at less risk of dying because they have already survived the
critical first month. Therefore, the relative risk of case-fatality is
considerably higher with later recurrent AMIs.
The present study confirms that the prognosis of myocardial
infarction has improved considerably during the last two
decades and demonstrates that this improvement extends to
patients with a recurrent AMI.
One-year incidence of recurrent AMI
One of the goals in the treatment of patients with AMI is to
prevent the occurrence of a new infarction. Apparently, this
goal is still elusive as evidenced by the disappointingly steady 1-
year reinfarction rate which remains at approximately 9.6%.
With the publication of new criteria for the diagnosis of AMI in
Europe and the United States, approximately 26% more
patients will be diagnosed as having AMI as compared with
the previously used WHO criteria.13In previous studies the 1-
year incidence of recurrent AMI among patients who have
survived the hospital phase of AMI varied from 6–7% in the
1980s1–3 14to approximately 2–4% in 1998–200l after the
introduction of modern invasive and non-invasive therapies.15–
17All these studies used the previous WHO definition of AMI.
We did not observe any significant increase in the rate of
reinfarction over the years, although reinfarction rates were
highest in 2000–2002. The higher rates of recurrent AMI in our
study compared to others probably reflect the non-selected
character of the study population which included all hospita-
lised patients with a first AMI in Denmark. By using only
primary discharge diagnoses, it is possible that admissions
might have been coded as, for instance, primary heart failure or
Days after first AMI
180 210240270 300330 3600
Log rank p<0.0001
Number of patients at risk
Cumulative mortality (%)
Unadjusted cumulative 1-year case-fatality after admission from first AMI stratified by period.
Demographics in relation to first AMI and recurrent AMI
Type of AMI
1985–19891990–1994 1995–19992000–2002p Value
Mean age, year (SD)
Male sex, %
Length of hospital stay, days*
Incidence at 1 year (%)
Early recurrent AMI, n (%)
Late recurrent AMI, n (%)
Mean age, year (SD)
Male sex, %
Length of hospital stay, days*
Recurrent AMI, recurrence within first year after initial AMI; early recurrent AMI, recurrence from 5 to 30 days after first AMI; late recurrent AMI, recurrence from 31 to
365 days after first AMI.
*Values are median (25% and 75% percentiles).
212 Buch, Rasmussen, Gislason, et al
unstable angina. The sensitivity of an AMI diagnosis increased
only slightly by adding secondary diagnoses (from 93% to 97%
for definite nonfatal AMI, from 65% to 68% for possible
nonfatal AMI and from 56% to 72% for fatal definite AMI).
However, the majority of diagnoses (86%) were coded as
Case-fatality after first and recurrent AMI
The relative decrease in 1-year case-fatality was about 50% for
both a first and a recurrent AMI during 1985–2002. Notably,
not only the trend but also the crude 1-year case-fatality of
patients with recurrent AMI were remarkably similar to those
of patients with first AMI (figs 1 and 2). This paradoxical
finding can best be explained by the fact that patients with
recurrent AMI are hospital survivors of AMI and therefore
represent a selected group of patients. The decrease in crude
case-fatality after a first and recurrent AMI is consistent with
findings from other population-based studies.18–22Similar, the
prognostic impact after a recurrent AMI weakened during the
study period. Patients with early reinfarction in 1985–1989 had
a 1-year case-fatality that was 7.5 times higher than that of
patients without reinfarction. In 2000–2002, this ratio had
declined to 2.1. A decline, though less pronounced, was also
seen in patients with late occurring reinfarctions.
In studies conducted before the 1990s, the relative risk of
dying within the first year was around 5–6 in patients with
recurrent AMI compared to patients without reinfarction.2–4We
found a higher risk of death in this unselected population,
which might also have been caused by the limited adjustment
for other factors that affect the prognosis after AMI. As no
30 6090 120150
Days after recurrent AMI
180 210240 270300 3303600
Log rank p<0.0001
Number of patients at risk
Cumulative mortality (%)
Unadjusted cumulative 1-year case-fatality after admission from first recurrent AMI stratified by period.
compared to hospital survivors without a recurrent AMI during 1985–2002
Relative risk of sex- and age-adjusted 1-year case-fatality mortality after a first AMI among patients with a recurrent AMI
1985–1989 1990–19941995–1999 2000–2002
No re-AMI day 5–30*
Re-AMI day 5–30
RR* (95% CI)
No re-AMI day 5–365*
Late recurrent AMI day 31–365
RR (95% CI)?
7.5 (6.9 to 8.5)
4.8 (4.3 to 5.2)
3.2 (2.8 to 3.6)
2.1 (1.9 to 2.5)
11.7 (11.0 to 12.4)
8.5 (8.0 to 9.1)
6.3 (5.8 to 6.9)
5.6 (5.1 to 6.2)
Numbers of deaths in each category of patients during first year are shown.
RR, relative risk; CI, confidence interval.
*Reference group for early recurrent AMI is hospital survivors after first AMI without a recurrent AMI during the first 30 days after index admission; ?reference group for
late recurrent AMI is hospital survivors who where alive 30 days after admission, and without a recurrent AMI during the first year after admission. Adjustment was
made for sex and age.
Decline in mortality from recurrent AMI 1985 to 2002213
studies in recent years have extended follow-up to 1 year after
reinfarction (occurring within the first year), we are unable to
compare our findings from the latest period, but in-hospital
recurrence has been associated with a relative risk of death of
2–4 during the first year after the event.23 24Only one previous
study has specifically investigated the trend in 1-year mortality
from a recurrent AMI.25Based on an unselected population of
1415 patients with recurrent AMI in 1981–1983 and 1093
patients in 1992–1996, Shotan et al found a reduction in crude
1-year case-fatality from 39% in 1981–1983 to 26% in 1992–
1996, which is in accordance with our findings.
There are a number of reasons for this change in the
prognostic significance of a recurrent AMI. These factors extend
from improvement in medical therapy and prophylaxis, and
altered patient behaviour through primary care physician
referral to emergency rooms, as well as changes in coding
practice. New diagnostic criteria and a lower threshold for
hospital admission of patients with chest pain may lead to the
diagnosis of additional patients with smaller and less serious
infarctions. However, in a previous study Abildstrom et al
investigated the impact of troponin use in the same population
and found that the decline in case-fatality from a first AMI
during 1995–2002 was unaffected by the introduction of
troponins.26This is in accordance with most other studies,
which have demonstrated an even higher mortality among the
additional patients identified by troponins.27 28Therefore, it is
unlikely that the decline in case-fatality presented in our paper
is simply caused by changes in AMI definitions over the years.
It is noteworthy that most of the reduction in case-fatality was
achieved during the early period after recurrent AMI, indicating
a more aggressive treatment during hospitalisation and in the
early phase after hospitalisation. The health care system in
Denmark is comparable to that in other western countries;
however, the level of revascularisations was among the lowest
in the early 1990s.29In 1993 a national heart plan was
introduced to increase the frequency of invasive procedures
and in 2001 rates of revascularisation were comparable to those
in the rest of Europe.30Unfortunately, the use of percutaneous
coronary intervention (PCI) was coded infrequently in the
National Patient Registry before 1999, but in 2002 the rate of
PCI performed during the first week after admission was 21.4%
among patients with first AMI who experienced a later
Study strengths and limitations
Administrative registers have the advantage that numbers can
become large, and the disadvantage that data are limited. Due
to the large population we avoided pooling of data from several
years, which allowed us to investigate trends over time.
Furthermore, the population was unselected and thus our
results are not limited to a certain category of AMI patients.
However, this study has some limitations. We had no access to
clinical variables or risk factors and therefore no information
was provided regarding mechanism of death, pathophysiologi-
cal explanations of the observed findings, or case severity of
first and recurrent AMI. However, the aim of the study was to
describe the combined impact of time and diagnostic criteria on
the prognostic importance of a recurrent AMI, and in this
respect administrative registers are the only option. Other
limitations include the use of a 5-day cut-point for read-
missions. As the length of hospital stay decreased significantly
during the study period, this may have introduced bias because
fewer reinfarctions would have been identified in early periods.
If early reinfarctions where unrecognised due to longer
hospitals stay, this would tend to increase case-fatality in the
non-reinfarction group, and thereby reduce the decline in case-
fatality after reinfarction over the years.
Furthermore, we were unable to register recurrent AMIs
occurring during the initial hospitalisation or AMI occurring
during revascularisation. Accordingly, periprocedural AMI
might appear in our data, but only if the AMI was considered
the main medical diagnosis as we only used the primary
discharge diagnosis in this study. Finally, different thresholds
for hospitalisation of patients with suspected AMI over the
years may be a confounding factor.
During the latest two decades the decline in case-fatality after a
recurrent AMI was similar to the decline in case-fatality after a
first AMI. Recurrent AMI remained a significant predictor of
death despite changes in AMI diagnostic criteria, but the
prognostic impact has weakened over the years indicating a
shift towards a better prognosis.
P Buch, C Torp-Pedersen, Department of Cardiovascular Medicine,
Bispebjerg University Hospital, Bispebjerg Bakke 23, DK-2400
Copenhagen NV, Denmark
S Rasmussen, J N Rasmussen, M Madsenb, National Institute of Public
Health, Øster Farimagsgade 5, DK-1399 Copenhagen K, Denmark
G H Gislason, S Stender, S Z Abildstrom, Department of Cardiology,
Gentofte University Hospital, Niels Andersens Vej 65, DK-2900 Hellerup,
L Køber, Department of Cardiology, The Heart Centre, Rigshospitalet,
Copenhagen University Hospital, Blegdamsvej 9, DK-2100 Copenhagen,
N Gadsbøll, Department of Medicine, Roskilde County Hospital, Køgevej
7–13, DK-4000 Roskilde, Denmark
Financial support: This study was supported by a grant from the Danish
Heart Foundation (grant number 04-10-B76-A217-22196).
Competing interest: None.
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IMAGES IN CARDIOLOGY ............................................................... .................
Spontaneous coronary vasospasm in the catheterisation laboratory: prompt resolution after atropine
week before, she had sustained an acute
inferior wall myocardial infarction for which
she had received intravenous streptokinase.
Her hospital course was uneventful. Risk
factors were smoking and premature meno-
pause. Physical examination was unremark-
After selective angiography of the left
coronary system, which was normal, she
developed nausea, profuse sweating, a sinus
bradycardia of 25 beats/min, hypotension with
a blood pressure of 60/30 mm Hg and chest
pain. ST segment elevation was seen in
monitor lead II. The patient was given 1 mg
intravenous atropine. Volume loading with
normal saline was started. At the same time,
right coronary angiography was performed
and a total obstruction was seen in the mid-
right coronary artery (panel A). At about
1 min after giving atropine, all signs and
symptoms resolved and control right coronary
injection showed noobstructionat all
(panel B). The patient was sent to bed and
metoprolol was replaced by diltiazem.
In the literature, there is only one report in
which atropine reversed spontaneous coronary
vasospasm and haemodynamic decompensa-
tion, which were possibly due to vagal reaction
in the catheterisation laboratory as our case.
56-year-old woman was referred to us
for angiography because of recent infer-
ior wall myocardial infarction. One
In that case, in contrast with ours, the spasm was multivessel, and after spasm resolved, it has
been seen that diffuse atherosclerotic lesions were present.
From this case we suggest that, in the presence of vagal symptoms and coronary artery
occlusion, atropine might be useful to rule out coronary vasospasm.
(A) Total occlusion of mid-right coronary artery. Left anterior oblique projection. (B) Resolution of the
spasm after intravenous atropine. Left anterior oblique projection.
Decline in mortality from recurrent AMI 1985 to 2002 215