ORIGINAL RESEARCH ARTICLE

ORIGINAL RESEARCH
ARTICLE
Acute Myocardial Infarction
Changes in Patient Characteristics, Management, and 6-Month
Outcomes Over a Period of 20 Years in the FAST-MI Program
(French Registry of Acute ST-Elevation or Non-ST-elevation
Myocardial Infarction) 1995 to 2015

BACKGROUND: ST-segmentelevation myocardial infarction (STEMI) and Etienne Puymirat, MD,

nonST-segmentelevation myocardial infarction (NSTEMI) management PhD
has evolved considerably over the past 2 decades. Little information et al
Downloaded from http://circ.ahajournals.org/ by guest on August 27, 2017

on mortality trends in the most recent years is available. We assessed

trends in characteristics, treatments, and outcomes for acute myocardial
infarction in France between 1995 and 2015.
METHODS: We used data from 5 one-month registries, conducted 5
years apart, from 1995 to 2015, including 14423 patients with acute
myocardial infarction (59% STEMI) admitted to cardiac intensive care units
in metropolitan France.
RESULTS: From 1995 to 2015, mean age decreased from 6614
to 6314 years in patients with STEMI; it remained stable (6814
years) in patients with NSTEMI, whereas diabetes mellitus, obesity,
and hypertension increased. At the acute stage, intended primary
percutaneous coronary intervention increased from 12% (1995) to 76%
(2015) in patients with STEMI. In patients with NSTEMI, percutaneous
coronary intervention 72 hours from admission increased from 9%
(1995) to 60% (2015). Six-month mortality consistently decreased in
patients with STEMI from 17.2% in 1995 to 6.9% in 2010 and 5.3% in
2015; it decreased from 17.2% to 6.9% in 2010 and 6.3% in 2015 in
patients with NSTEMI. Mortality still decreased after 2010 in patients with
STEMI without reperfusion therapy, whereas no further mortality gain was
found in patients with STEMI with reperfusion therapy or in patients with The full author list is available on
page 10 and 11.
NSTEMI, whether or not they were treated with percutaneous coronary
intervention. Correspondence to: Nicolas
Danchin, MD, PhD, Hpital
CONCLUSIONS: Over the past 20 years, 6-month mortality after acute Europen Georges Pompidou,
Department of Cardiology, 20
myocardial infarction has decreased considerably for patients with STEMI rue Leblanc, 75015 Paris, France.
and NSTEMI. Mortality figures continued to decline in patients with STEMI E-mail nicolasdanchin@yahoo.fr
until 2015, whereas mortality in patients with NSTEMI appears stable Sources of Funding, see p XXX
since 2010.
KEY WORDS: coronary artery
disease mortality non-ST
elevated myocardial infarction
percutaneous coronary
intervention ST elevation
myocardial infarction
2017 American Heart
Association, Inc.

Circulation. 2017;136:0000. DOI: 10.1161/CIRCULATIONAHA.117.030798 September 5, 2017 1

 Puymirat et al
Clinical Perspective
What Is New?
Previous observational studies have shown a con-
tinuous decline in mortality in patients with ST-
segmentelevation and nonST-segmentelevation
myocardial infarction, but no studies beyond the
early 2010s have analyzed trends in management
and mortality.
We observed major changes in the characteristics
and management of both patients with ST-
segmentelevation and nonST-segmentelevation
myocardial infarction over the past 20 years.
Together with these changes, 6-month mortality
has consistently declined in patients with ST-
segmentelevation myocardial infarction, whereas,
in patients with nonST-segmentelevation myo-
cardial infarction, 6-month mortality reached a pla-
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teau after 2010.
What Are the Clinical Implications?
For patients presenting with ST-segmentelevation
or nonST-segmentelevation myocardial infarc-
tion, adoption of recommended strategies, such
as promoted by current guidelines, is associated
with improved outcomes and should be strongly
encouraged.
Acute-stage mortality has become extremely low in
comparison with what was observed 20 years ago,
and is not likely to further improve by much.
The future challenges will be to reduce prehospi-
tal mortality (out-of-hospital sudden death) and to
improve long-term survival after the acute event,
both by increasing the adoption of recommended
secondary prevention and by developing new pre-
ventative strategies.
T
he early outcome of patients with acute myo-
cardial infarction (AMI) has improved consider-
ably.16 Among patients with AMI, however, the
pathophysiology, management, and outcomes differ
between those with ST-segmentelevation myocardial
infarction (STEMI) and nonST-segmentelevation myo-
cardial infarction (NSTEMI). Traditionally, patients with
NSTEMI have a substantially lower early mortality than
those with STEMI, but a higher risk of long-term mor-
tality, likely explained by more frequent risk factors and
comorbidities, and a greater burden of coronary artery
disease.79
The improvement in early outcomes up to the ear-
ly 2010s has been attributed to changes in patient
populations, more frequent use of revascularization
procedures, and increased use of recommended medi-
cations.5,6,1012 Since 2010, however, little information
is available on early outcomes in real-world settings,
although the use of percutaneous coronary interven-
2 September 5, 2017
tions (PCIs) has continued to increase and newer anti-
thrombotic agents have become available and are now
widely used. Whether these changes in the most recent
years have translated into improved early survival, and
whether trends in early outcomes differ between pa-
tients with STEMI and those with NSTEMI is not known.
The aim of the present study was to assess trends in
6-month mortality in patients with STEMI and NSTEMI,
according to their profile and initial management in 5
sequential nationwide French surveys conducted be-
tween 1995 and 2015.1317
METHODS
Patient Population
Five nationwide French registries were conducted 5 years
apart over a 20-year period (19952015): USIK 1995,13
USIC (Unit de Soins Intensifs Coronaires) 2000,14 FAST-MI
(French Registry of Acute ST-Elevation or non-ST-elevation
Myocardial Infarction) 2005 (NCT00673036),15 FAST-MI 2010
(NCT01237418),16 and FAST-MI 2015 (NCT02566200)17
(Methods I in the online-only Data Supplement). The meth-
ods used for these registries have been detailed previ-
ously.1317 In brief, their primary objectives were to evaluate
the characteristics, management, and outcomes of patients
with AMI, as seen in routine clinical practice, on a country-
wide scale.
All 5 registries consecutively included patients with STEMI
or NSTEMI admitted to cardiac intensive care units within 48
hours of symptom onset, during a specified 1-month period
(November 1995 and 2000, October to December 2005,
2010, and 2015). AMI was defined by increased levels of car-
diac biomarkers (troponins, creatine kinase [CK], or CK-MB)
together with either compatible symptoms or ECG changes.
Patients who died soon after admission and for whom cardiac
markers were not measured were included if they had signs
or symptoms associated with typical ST-segment changes.
Exclusion criteria were (1) refusal to participate; (2) iatrogenic
myocardial infarctions, defined as occurring within 48 hours
of any therapeutic procedure; and (3) AMI diagnosis invali-
dated in favor of another diagnosis. STEMI was diagnosed
when ST-segment elevation 1 mm was seen in at least 2
contiguous leads in any location on the index or qualifying
ECG, or when presumed new left bundle-branch block or
documented new Q waves were observed. In the absence of
ST-segment elevation, patients meeting the inclusion criteria
were considered to have NSTEMI.
Participation in the study was offered to all institutions,
including university teaching hospitals, general and regional
hospitals, and private clinics receiving AMI emergencies.
Physicians were instructed that the study should not affect
clinical care or management. The study was conducted in
accordance with the guidelines on good clinical practice and
French law. The study protocols for all surveys were reviewed
by the relevant Committees for the Protection of Human
Subjects. Data file collection and storage were approved
by the Commission Nationale Informatique et Libert. All
patients were informed of the nature and the aims of the
surveys and could request to be excluded; in addition, written
consent was obtained for the 2005, 2010, and 2015 surveys.
Circulation. 2017;136:0000. DOI: 10.1161/CIRCULATIONAHA.117.030798

Data Collection
Data on baseline characteristics, including demographics
(age, sex, and body mass index), risk factors (hypertension,
diabetes mellitus, current smoking, hypercholesterolemia, and
family history of coronary artery disease), and medical history
(myocardial infarction, stroke, heart failure, and peripheral
artery disease), were collected as previously described.1317
Information on the use of cardiac procedures, including the
use of PCI, use of medications (anticoagulants, antiplatelet
agents, diuretics, -blockers, angiotensin-converting enzyme
inhibitors or angiotensin receptor blockers, and lipid-lowering
agents) in the first 48 hours (or first 5 days, for the 1995
survey) and at-hospital discharge (except for the 1995 survey)
was collected. Full appropriate medical therapy was defined
as concomitant use of antiplatelet agents, statins, angio-
tensin-converting enzyme inhibitors or angiotensin receptor
blockers, and -blockers when appropriate (Methods II in the
online-only Data Supplement). Several additional variables
were also collected in the most recent surveys.
Information on mortality was obtained directly by the local
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investigators for the 1995 and 2000 surveys. For the 2005,
2010, and 2015 surveys, follow-up was centralized at the
French Society of Cardiology.
Statistical Analysis
Continuous variables are reported as means (SDs) or medians
and interquartile ranges, when appropriate. Discrete variables
are described as counts and percentages. Groups were com-
pared by analysis of variance for continuous variables and 2
or Fisher exact tests for discrete variables. Temporal trends
were tested using linear-by-linear association tests for binary
and Jonckheere-Terpstra tests for continuous variables. Odds
ratios and hazard ratios (HRs) are presented with their 95%
confidence intervals (CIs).
To determine independent predictors of the use of proce-
dures (reperfusion therapy in STEMI, PCI 72 hours of admis-
sion in NSTEMI), binary logistic regression analyses were used,
using the same covariables as those listed below.
To account for changes in the baseline characteristics of
the populations admitted from 1995 to 2015, we calculated
risk scores for the 2015 STEMI and NSTEMI populations, using
multiple logistic regression analysis including demographic
data, risk factors, medical history, body mass index (using
imputed values based on sex and age for the 6% of patients
with missing values), and region. This risk score, calculated
from the baseline characteristics of the 2015 population
(c-statistic, 0.805 for the STEMI and 0.80 for the NSTEMI),
was used to standardize the death rates for each of the previ-
ous surveys. The standardized death rates therefore represent
the rates that would have been expected had the distribution
of the baseline characteristics of each of the first 4 surveys
been similar to that of the most recent one.
Multivariable analyses of correlates of 6-month mortal-
ity were performed using Cox backward stepwise multiple
logistic regression, using a threshold of 0.10 for variable
elimination. Beside time period, variables included in the final
models were selected ad hoc, based on their physiological
relevance and potential to be associated with outcomes; they
comprised age, sex, risk factors, comorbidity, anterior location
of myocardial infarction for STEMI, type of institution, and
Circulation. 2017;136:0000. DOI: 10.1161/CIRCULATIONAHA.117.030798
20-Year Trends in STEMI and NSTEMI
ORIGINAL RESEARCH
region. A sensitivity analysis was performed, adding peak CK
to the covariates in the main analysis.
ARTICLE
To assess the relationship between early management and
6-month survival, further analyses also used in-hospital PCI,
type of anticoagulants used, and use of antiplatelet agents,
-blockers, statins, and angiotensin-converting enzyme inhib-
itors or angiotensin receptor blockers during the first 2 days
(5 days for the 1995 survey) as covariables, and in 3-day sur-
vivors to avoid healthy survivor bias.
Analyses were repeated by using forward stepwise analy-
sis to check the consistency of the results. Collinearity was
tested by calculation of variance inflation factors. Statistical
analyses were performed by using IBM SPSS 23.0 (IBM SPSS
Inc). For all analyses, 2-sided P values <0.05 were considered
significant.
RESULTS
Study Population
In total, 14423 patients with AMI were enrolled in the
5 surveys. Of all centers managing patients with AMI,
62% (312 centers, 2152 patients) participated in 1995,
83% in 2000 (369 centers, 2317 patients), 60% in
2005 (223 centers, 3059 patients), 76% in 2010 (213
centers, 3079 patients), and 78% in 2015 (204 centers,
3813 patients). Over the 20-year period, the propor-
tion of NSTEMI in the surveys increased: 29% in 1995,
21% in 2000, 47% in 2005, 44% in 2010, and 51% in
2015, corresponding to a change in operational diag-
nosis of NSTEMI (based on CK up to 2000, troponins in
2005 and 2010, and mostly high-sensitivity troponins
in 2015).
In patients with STEMI, mean age decreased from
66.214.0 to 63.514.6 years, current smoking in-
creased, as did the prevalence of obesity, hypertension,
hypercholesterolemia, and diabetes mellitus, whereas
history of cardiovascular disease decreased (Table1).
In patients with NSTEMI, mean age, sex, and cur-
rent smoking did not vary; hypertension, hypercholes-
terolemia, obesity, and diabetes mellitus increased. In
contrast, history of heart failure and peripheral artery
disease decreased (Table2).
Early Management
In patients with STEMI, median time from symptom
onset to hospital admission decreased from 240 (in-
terquartile range, 140540) minutes to 168 minutes
(interquartile range, 100398); time from onset to
first call decreased from 2000 to 2010 and increased
between 2010 and 2015, whereas the use of mobile
intensive care units increased (Table 1). Reperfusion
therapy consistently increased over time, from 49.5%
to 82% (adjusted odds ratio 2015 versus 1995, 4.39;
95% CI, 3.735.18, P<0.001), with more frequent
use of primary PCI (12%76%) and less frequent use
of fibrinolysis (37.5%6%) (Figure I in the online-
September 5, 2017 3
 Puymirat et al

Table 1. Baseline Characteristics and Early Hospital Management of Patients With ST-SegmentElevation
Myocardial Infarction From 1995 to 2015
USIK 1995* USIC 2000* FAST-MI 2005 FAST-MI 2010 FAST-MI 2015
(n=1536) (n=1844) (n=1611) (n=1716) (n=1872) P Value
Demography
Age, y 66.214.0 64.514.6 64.014.7 63.314.5 63.513.8 <0.001
Female, n (%) 431 (28) 499 (27) 458 (28) 423 (25) 469 (25) 0.04
Risk factors, n (%)
Hypertension 673 (44) 804 (44) 792 (49) 806 (47) 835 (45) 0.006
Hypercholesterolemia 534 (35.5) 719 (39.5) 699 (43) 675 (39) 678 (36) <0.001
Diabetes mellitus 242 (16) 364 (20) 302 (19) 283 (16.5) 308 (16.5) 0.01
Current smoking 491 (32) 651 (35) 600 (37) 701 (41) 789 (42) <0.001

Obesity (BMI 30) 208 (14) 269 (16) 299 (21) 324 (20) 349 (19.5) <0.001
Cardiovascular history and comorbidities, n (%)
Myocardial infarction 225 (15) 276 (15) 180 (11) 187 (11) 231 (12) <0.001
PCI 139 (7.5) 140 (9) 175 (10) 236 (13) <0.001
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CABG 50 (3) 34 (2) 96 (6) 32 (2) <0.001

Stroke or TIA 96 (6) 78 (4) 91 (6) 68 (4) 86 (5) 0.009
Heart failure 98 (6) 84 (5) 56 (3.5) 41 (2) 54 (3) <0.001
PAD 148 (10) 145 (8) 85 (5) 83 (5) 84 (4.5) <0.001
CKD 66 (4) 50 (3) 42 (2) 61 (3) 0.26
Medications before, n (%)
Antiplatelet therapy 389 (21) 336 (21) 335 (19.5) 490 (26) <0.001
Statin 304 (16.5) 342 (21) 374 (22) 398 (21) <0.001

-Blocking agent
 338 (18) 296 (18) 313 (18) 341 (18) 0.99
ACE-I or ARB 349 (19) 395 (24.5) 478 (28) 449 (24) <0.001
Initial pathway, n (%)
Mobile ICU 427 (23) 666 (41) 837 (49) 953 (51) <0.001
Time delays, median [IQR]
Onset to first call/medical contact 120 90 74 90
<0.001
[40360] (n=1486) [30295] (n=1600) [30240] (n=1674) [30300] (n=1872)
Onset to admission 240 255 200 175 168
<0.001
[140540] (n=1427) [150540] (n=1706) [120430] (n=1610) [107380] (n=1698) [100398] (n=1843)
First call/medical contact to
primary PCI

Direct admission 165 140 131
<0.001
[110240] (n=552) [106196] (n=1039) [99195] (n=1529)

Transfer-in 230 240 214
0.467
[150389] (n=107) [156379] (n=270) [150366] (n=358)
Presentation at admission
Heart rate, meanSD, bpm 78.219.0 78.319.7 78.020.9 77.317.4 0.263
SBP, meanSD, mmHg 13227 13528 141.228 134.326 0.001
Peak creatine kinase, U/L

Mean (SD) 919 (928) 774 (781) 554 (805) 487 (779) 425 (673) <0.001
No. of patients 585 452 1264 1015 876
Reperfusion therapy, n (%)
None 777 (51) 870 (47) 495 (31) 331 (19) 339 (18) <0.001
Lysis 576 (37.5) 545 (30) 463 (29) 238 (14) 116 (6)
Primary PCI 183 (12) 429 (23) 653 (40.5) 1147 (67) 1417 (76)

(Continued)

4 September 5, 2017 Circulation. 2017;136:0000. DOI: 10.1161/CIRCULATIONAHA.117.030798

 20-Year Trends in STEMI and NSTEMI

ORIGINAL RESEARCH
Table 1.Continued

ARTICLE
USIK 1995* USIC 2000* FAST-MI 2005 FAST-MI 2010 FAST-MI 2015
(n=1536) (n=1844) (n=1611) (n=1716) (n=1872) P Value
Procedures during hospitalization, n (%)
CAG 1489 (81) 1449 (90) 1652 (96) 1846 (99) <0.001
PCI 300 (19.5) 1132 (61) 1221 (76) 1488 (87) 1682 (90) <0.001
Left ventricular ejection fraction (%) 4913 5214 5113 5011 5010 0.228
Medications in first 48 h, n (%)
Antiplatelet therapy 1419 (92) 1759 (95) 1544 (96) 1672 (97) 1864 (100) <0.001
Thienopyridine 1425 (88.5) 1682 (98) 1809 (97) <0.001
Clopidogrel 1415 (88) 1459 (85) 509 (27) <0.001
Prasugrel 571 (33) 457 (24) <0.001
Ticagrelor 1102 (59)
GPIIb/IIIa inhibitors 351 (19) 614 (38) 732 (43) 441 (24) <0.001
UFH 1481 (96) 1463 (79) 1074 (67) 768 (45) 1022 (55) <0.001
LMWH 506 (27) 986 (61) 1069 (62) 1146 (61) <0.001
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Fondaparinux 232 (13.5) 352 (19) <0.001

Bivalirudine 76 (4) 121 (6.5) 0.008
Statin 151 (10) 842 (46) 1262 (78) 1543 (90) 1576 (84) <0.001

-Blocking agents
 1001 (65) 1348 (73) 1162 (72) 1384 (81) 1421 (75) <0.001
ACE-I or ARB 733 (48) 764 (41) 853 (53) 1112 (65) 1201 (64) <0.001
Diuretics 532 (35) 447 (24) 417 (26) 411 (24) 458 (24.5) <0.001
Appropriate recommended
109 (7) 506 (27) 763 (47) 115 (65) 1145 (62) <0.001
therapy

Data are presented as n (%) or meanSD. ACE-I indicates angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker; BMI, body mass index;
CABG, coronary artery bypass graft surgery; CAG, coronary angiography; CKD, chronic kidney disease; FAST-MI, French Registry of Acute ST-Elevation or non-ST-
elevation Myocardial Infarction; GP, glycoprotein; ICU, intensive care unit; IQR, interquartile range; LMWH, low-molecular-weight heparin; PAD, peripheral artery
disease; PCI, percutaneous coronary intervention; SBP, systolic blood pressure; TIA, transient ischemic attack; UFH, unfractionated heparin; and USIC, Unit de Soins
Intensifs Coronaires.
* For 1995 and 2000, blank cells indicate data not available.
Minutes; median [25th75th percentiles].
For 1995, medications used at any time during the first 5 days.

only Data Supplement). Coronary angiography dur-
ing the index admission increased to reach 99% in
2015; in-hospital PCI increased from 19.5% to 90%.
Use of evidence-based treatments during the first 48
hours from admission increased gradually; among
P2Y12 inhibitors, there was a shift from clopidogrel
to prasugrel and ticagrelor in the most recent surveys;
unfractionated heparin decreased, and low-molecular-
weight heparins or news anticoagulants (bivalirudine,
fondaparinux) increased. Overall, the early use of
full appropriate therapy increased from 7% in 1995
to 62% in 2015. Cardioverter defibrillators were im-
planted during the hospital stay in 0% (2005), 0.1%
(2010), and 0.6% (2015). At hospital discharge, the
proportion of patients receiving recommended medi-
cations consistently increased from 2000 to 2010 and
remained stable in 2015 (Table I in the online-only
Data Supplement).
In patients with NSTEMI, the use of early PCI (72
hours from admission) increased from 9% to 60%
(adjusted odds ratio 2015 versus 1995, 16.4; 95% CI,
12.022.4, P<0.001) (Figure I in the online-only Data
Supplement), and PCI during the initial hospital stay
increased, from 12.5% to 67%, as did the use of coro-
nary angiography at any time during the index admis-
sion increased, to reach 95% in 2015. Trends similar to
those found in patients with STEMI were observed for
evidence-based treatments within 48 hours of admis-
sion, as for discharge medications (Table2, Table I in the
online-only Data Supplement).
Outcomes
In-hospital complications decreased, as did 30-day
mortality (from 14% to 3% in patients with STEMI and
from 11% to 3% in patients with NSTEMI) (Tables II and
III in the online-only Data Supplement).
Six-month mortality decreased from 17.2% to 5.3%
in patients with STEMI. Adjusted HR for 6-month death
in reference to 1995 consistently decreased over time,
to 0.32 (95% CI, 0.260.41) in 2015. Standardized
death rates decreased continuously from 15.4% in
1995 to 6.8% in 2010, and 5.3% in 2015 (Figure II in
the online-only Data Supplement).

Circulation. 2017;136:0000. DOI: 10.1161/CIRCULATIONAHA.117.030798 September 5, 2017 5

 Puymirat et al

Table 2. Baseline Characteristics and Early Hospital Management of Patients With NonST-Segment
Elevation Myocardial Infarction From 1995 to 2015
USIK 1995* USIC 2000* FAST-MI 2005 FAST-MI 2010 FAST-MI 2015
(n=616) (n=476) (n=1448) (n=1363) (n=1941) P for Trend
Demography
Age, y, meanSD 68.514.2 68.913.5 70.213.3 68.613.6 68.113.5 <0.001
Female, n (%) 188 (30.5) 130 (27) 510 (35) 406 (30) 581 (30) 0.75
Risk factors, n (%)
Hypertension 303 (50) 272 (57) 962 (66) 847 (62) 1220 (63) <0.001
Hypercholesterolemia 221 (37) 225 (48) 749 (52) 653 (48) 979 (54) <0.001
Diabetes mellitus 122 (20) 123 (26) 422 (29) 370 (27) 522 (27) 0.001
Current smoking 157 (26) 103 (22) 322 (22) 334 (24.5) 566 (29) 0.75

Obesity (BMI 30) 77 (13) 93 (22.5) 268 (21) 306 (24) 468 (25) <0.001

Cardiovascular history and comorbidities, n (%)

Myocardial infarction 169 (27) 135 (28) 345 (24) 311 (23) 469 (24) 0.055
PCI 77 (16) 260 (18) 314 (23) 462 (24) <0.001
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CABG 48 (10) 132 (9) 116 (8.5) 124 (6) 0.006

Stroke or TIA 44 (7) 33 (7) 141 (10) 71 (5) 143 (7) <0.001
Heart failure 100 (16) 65 (14) 117 (8) 105 (8) 148 (8) <0.001
PAD 73 (12) 70 (15) 197 (14) 161 (12) 190 (10) 0.003
CKD 42 (9) 113 (8) 87 (6) 136 (7) 0.25
Medications before, n (%)
Antiplatelet therapy 192 (40) 610 (42) 538 (39.5) 828 (43) 0.28
Statin 119 (25) 472 (33) 490 (36) 712 (37) <0.001

-Blocker
 132 (28) 437 (30) 425 (31) 646 (33) 0.07

ACE-I or ARB 147 (31) 615 (42.5) 552 (40.5) 734 (38) <0.001
Presentation at admission
Heart rate, meanSD, bpm 82.922.0 81.020.9 81.119.9 79.019.6 <0.001
SBP, meanSD, mmHg 14027 14328.5 14828 14527 <0.001
Peak creatine kinase, U/L <0.001

Mean (SD) 919 (928) 774 (781) 554 (805) 487 (779) 425 (673)
No. of patients 585 452 1264 1015 876
Procedures
Coronary angiography, n (%) 338 (71) 1133 (78) 1232 (90) 1852 (95) <0.001
PCI, n (%) 77 (12.5) 209 (44) 736 (51) 892 (65) 1292 (67) <0.001

PCI 24 h 41 (7) 65 (14) 363 (25) 529 (39) 701 (36) <0.001

PCI 72 h 55 (9) 118 (25) 558 (38.5) 745 (55) 1156 (60) <0.001

Left ventricular ejection fraction (%) 5214 5415 5314 5311 5311 0.775
Medications in first 48 h, n (%)
Antiplatelet therapy 546 (89) 445 (93.5) 1365 (94) 1338 (98) 1905 (98) <0.001
Clopidogrel 1193 (82) 1223 (90) 790 (41) <0.001
Prasugrel 183 (13) 98 (5) <0.001
Ticagrelor 1000 (51.5)
GPIIb/IIIa inhibitors 59 (12) 491 (34) 330 (24) 115 (6) <0.001
UFH 583 (95) 298 (63) 692 (48) 520 (38) 1062 (55) <0.001
LMWH 194 (41) 959 (66) 818 (60) 965 (50) <0.001
Bivalirudine 0 0 0 19 (1) 22 (1) 0.51
Fondaparinux 0 0 0 239 (17.5) 667 (34) <0.001

(Continued)

6 September 5, 2017 Circulation. 2017;136:0000. DOI: 10.1161/CIRCULATIONAHA.117.030798

 20-Year Trends in STEMI and NSTEMI

ORIGINAL RESEARCH
Table 2.Continued

ARTICLE
USIK 1995* USIC 2000* FAST-MI 2005 FAST-MI 2010 FAST-MI 2015
(n=616) (n=476) (n=1448) (n=1363) (n=1941) P for Trend
Statin 62 (10) 203 (43) 1021 (70.5) 1161 (85) 1521 (78) <0.001

-Blocker
 372 (60) 306 (64) 955 (66) 1055 (77) 1377 (71) <0.001

ACE-I or ARB 259 (42) 174 (37) 741 (51) 837 (61) 1100 (57) <0.001
Diuretics 236 (38) 166 (35) 585 (40) 452 (33) 644 (33) <0.001
Appropriate recommended therapy 34 (5.5) 118 (25) 611 (42) 853 (63) 1109 (58) <0.001

Data are presented as n (%) or meanSD. ACE-I indicates angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker; BMI,
body mass index; CABG, coronary artery bypass graft surgery; CKD, chronic kidney disease; FAST-MI, French Registry of Acute ST-Elevation or non-
ST-elevation Myocardial Infarction; GP, glycoprotein; ICU, intensive care unit; LMWH, low-molecular-weight heparin; PAD, peripheral artery disease;
PCI, percutaneous coronary intervention; TIA, transient ischemic attack; UFH, unfractionated heparin; and USIC, Unit de Soins Intensifs Coronaires.
* For 1995 and 2000, blank cells indicate data not available.
For 1995, medications used at any time during the first 5 days.

In patients with NSTEMI, mortality decreased from
17.2% to 6.3%, and adjusted HR decreased to 0.40
(95% CI, 0.300.54) in 2010, remaining stable at 0.40
(0.300.52) in 2015 (Figure1). Results were similar when
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py and early medications were entered as covariables
(Table IV in the online-only Data Supplement). The re-
sults were stable after a sensitivity analysis censoring
patients who died within 3 days of admission. In pa-

peak CK was entered as an additional variable (Table IV
in the online-only Data Supplement). Standardized death
rates decreased continuously from 15.3% in 1995 to
6.2% in 2010 and were marginally higher at 6.3% in
2015 (Figure II in the online-only Data Supplement).
Outcomes in Relation to Early
Revascularization and Early Medications
In the whole STEMI population, mortality decrease re-
mained significant even when both reperfusion thera-
tients with reperfusion therapy, 6-month mortality de-
creased from 10.8% to 4.8%, with little additional gain
beyond 2010 (adjusted HR, 0.41; 95% CI, 0.290.57 in
2010; 0.36; 95% CI, 0.260.50 in 2015), whereas the
decrease in mortality persisted in those without early
reperfusion, from 23.4% to 7.4% (adjusted HR 0.60;
95% CI, 0.440.83 in 2010; 0.32, 95% CI, 0.210.49
in 2015) (Figure2).
In patients with NSTEMI, mortality decrease over
time was no longer significant (adjusted HR 2015 ver-
sus 1995, 0.95; 95% CI, 0.661.36) when use of early

Figure 1. Cumulative 6-month mortality in patients with STEMI and NSTEMI by year of survey.
CI indicates confidence interval; HR, hazard ratio; NSTEMI, nonST-segmentelevation myocardial infarction; and STEMI,
ST-segmentelevation myocardial infarction.

Circulation. 2017;136:0000. DOI: 10.1161/CIRCULATIONAHA.117.030798 September 5, 2017 7

 Puymirat et al
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Figure 2. STEMI population.
Trends in 6-month mortality according to use of reperfusion therapy. Adjusted hazard ratios presented with their 95% confi-
dence intervals. HR indicates hazard ratio; and STEMI, ST-segmentelevation myocardial infarction.
PCI and recommended medications were entered as
covariables. Early PCI (HR, 0.62; 95% CI, 0.500.77),
new anticoagulants (HR, 0.68; 95% CI, 0.570.82),
statins (HR, 0.76; 95% CI, 0.630.91), -blockers (HR,
0.55; 95% CI, 0.460.66), and angiotensin-converting
enzyme inhibitors or angiotensin receptor blockers (HR,
0.69; 95% CI, 0.580.82) were all associated with re-
duced 6-month mortality. In patients without early PCI
(72 hours from admission), mortality decreased until
2010 (HR, 0.53; 95% CI, 0.380.73) and remained
stable in 2015 (HR, 0.50; 95% CI, 0.360.68); in those
with early PCI, mortality also decreased until 2010 (HR,
0.40; 95% CI, 0.300.54) and was unchanged in 2015
(HR, 0.40; 95% CI, 0.300.52) (Figure3).
Finally, we assessed the association between the use
of reperfusion therapy (STEMI) or early PCI (NSTEMI)
and early use of newer parenteral anticoagulants and
recommended medications, with 6-month mortality,
not taking into account the survey period (Table V in
the online-only Data Supplement). In patients with STE-
MI, the use of primary PCI, fibrinolysis, anticoagulants
other than unfractionated heparin, and the appropriate
use of recommended medications were all strongly as-
sociated with lower mortality. Similar associations were
found in patients with NSTEMI.
DISCUSSION
The present study documents the major changes in the
characteristics and management of both patients with
STEMI and NSTEMI over the past 20 years. Together with
8 September 5, 2017
these changes, 6-month mortality has declined: in pa-
tients with STEMI, 6-month mortality has continued to
decrease with a further 22% reduction in standardized
mortality from 2010 to 2015; in contrast, in patients
with NSTEMI, 6-month mortality reached a plateau af-
ter 2010 (3% increase in standardized mortality from
2010 to 2015). Furthermore, in patients with STEMI,
mortality gain over time persists even after accounting
for reperfusion therapy, seeming partly related to im-
proved overall organization of care in the most recent
period (improved patient information to reduce onset-
to-call times, reduced number of centers taking care
of patients with STEMI, direct admission to PCI-capable
centers, etc), whereas in patients with NSTEMI, mortal-
ity gain seems essentially related to early management
with PCI and recommended medications.
To the best of our knowledge, there are no published
data reporting on trends in mortality of patients with
AMI beyond the early 2010s. Before that, most reports
showed increased use of primary PCI and recommend-
ed medications, with a concomitant decrease in early
mortality,5,6,1012 including in specific populations such
as the elderly.18 The only major exception to this general
finding is the Chinas PEACE registry (Patient-centered
Evaluative Assessment of Cardiac Events Retrospective
Study of Acute Myocardial Infarction): despite increased
use of primary PCI from 11% to 28% from 2001 to
2011, only a nonsignificant 18% reduction in mortality
was observed over this time period.19
In terms of patient characteristics, it is noteworthy
that the age of patients with STEMI declined, and that
Circulation. 2017;136:0000. DOI: 10.1161/CIRCULATIONAHA.117.030798

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Figure 3. NSTEMI population.
Trends in 6-month mortality according to the use of PCI within 72 hours of admission. Adjusted hazard ratios presented with
their 95% confidence intervals. HR indicates hazard ratio; NSTEMI, nonST-segmentelevation myocardial infarction; PCR,
percutaneous coronary intervention; and STEMI, ST-segmentelevation myocardial infarction.
peak CK also decreased with time, indicating that in-
farct size may currently be smaller than 20 years ago,
possibly because of better primary prevention or earlier
management.
It is impressive that invasive strategies have standard-
ized, both for patients with STEMI and with NSTEMI,
to the point that admission for AMI has now become
nearly synonymous with the use of coronary angiog-
raphy. The figures observed in the 2015 survey are
higher than those usually reported (eg, 54% in the
20092010 period in the MINAP registry [Myocardial
Ischaemia National Audit Project]),11 although very high
rates (93%) were already reported in 2007 for patients
with STEMI in the Swedish registry,10 or, for men in
Lombardia, 92% in 2010 in comparison with 72% only
in women20; likewise, in patients with NSTEMI, PCI was
generally less used in other countries, typically 19% in
the United Kingdom and 35% in Sweden.21 The impact
of invasive strategies may differ according to type of
AMI: in patients with STEMI, mortality gain over time
appears mediated both by the increased use of reperfu-
sion therapy and recommended medications, and also
by the organization of care aimed at shortening total
ischemic time and referring patients to centers with a
larger experience in STEMI care in the most recent pe-
riod, whereas in patients with NSTEMI, early manage-
ment with PCI and recommended medications appears
to explain the near-totality of mortality gain.
One of the remarkable findings of this study is that,
although there was very little change in the character-
istics of the patients in the 2 most recent surveys (2010
Circulation. 2017;136:0000. DOI: 10.1161/CIRCULATIONAHA.117.030798
20-Year Trends in STEMI and NSTEMI
ORIGINAL RESEARCH
ARTICLE
and 2015), both for patients with STEMI and NSTEMI,
6-month mortality continued to decrease in patients
with STEMI, whereas it remained stable in patients with
NSTEMI.
In patients with STEMI, although the percentage of
patients getting reperfusion therapy remained stable
between 2010 and 2015, primary PCI was used more
often, there was a switch from clopidogrel or prasu-
grel to ticagrelor; fondaparinux and bivalirudine were
used more often, although often concomitantly with
unfractionated heparin; finally, appropriate use of
recommended medications at the acute stage and at
discharge remained stable. Most of the improvement
in 6-month outcome was related to improved surviv-
al in patients who had not received early reperfusion
therapy, possibly related to the lower age of these pa-
tients in the most recent surveys (average age 66 years
in 2015 versus 71 years in 1995) and to higher use of
recommended medications, and subsequent use of PCI
during the hospital stay, as well (4% in 1995, 43% in
2000, 45% in 2005, 49% in 2010, and 65% in 2015).
Consequently, the mortality gain in the overall STEMI
population seems to have resulted from both an in-
crease in primary PCI (which had an intrinsically lower
mortality) and from improved survival in the remaining
patients not having received reperfusion therapy at the
acute stage.
In patients with NSTEMI, in contrast, despite a fur-
ther increase in the use of invasive strategies and PCI
within 3 days of admission, and the replacement of
clopidogrel with newer P2Y12 inhibitors, as well, and
September 5, 2017 9
 Puymirat et al
increased use of newer parenteral anticoagulants,
6-month mortality did not decrease beyond 2010. The
reasons for lack of further mortality gain in the most re-
cent survey remain speculative. In particular, following
the results of the Trial to Assess Improvement in TRITON
(Therapeutic Outcomes by Optimizing Platelet Inhibi-
tion With Prasugrel) and PLATO (Platelet Inhibition and
Patient Outcomes) trials, and subsequent guidelines, a
shift from the use of clopidogrel to the use of prasugrel
and, more recently, ticagrelor, was found and an impact
on outcomes would have been expected; it must be
pointed out, however, that we studied all-cause mortal-
ity and not a composite end point similar to the one of
the randomized trials, although ticagrelor was associ-
ated with reduced all-cause mortality, as well, in PLA-
TO.22,23 Because of the low mortality rates observed, it
may also be needed to have longer periods of follow-up
to document further improvement in survival.
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Limitations and Strengths
Beyond the usual limitations intrinsic to any observa-
tional cohort, and, in particular, the fact that associa-
tion between patient characteristics and management
(eg, type of anticoagulant used) do not imply a causal
relationship because some of the variables may be
fraught with uncorrected confounding, the FAST-MI
program has specific limitations that must be empha-
sized. None of the registries was population based, and
the total number of sites taking care of patients with
AMI changed over the study period, as a consequence
of deliberate health policy planning to avoid referral of
patients with AMI to small nonspecialized centers. Also,
the operational definition of NSTEMI changed with the
generalized use of troponin measurements and then of
high-sensitivity troponins, instead of CK, which was the
marker of myocardial injury used in the first 2 surveys.
Consequently, a large proportion of patients (those with
increased troponins but no elevated CK) in the 3 latter
surveys would not have been included in the 1995 and
2000 surveys, because they would have been consid-
ered to present with unstable angina; we did, however,
use CK values in the multivariable analyses to adjust for
these differences in initial patient profiles. The 1:1 ratio
of NSTEMI and STEMI in the most recent surveys may
appear intriguing; it must be noted that, in contrast
with several other registries, we did not include patients
with unstable angina (who are usually included among
nonST-segmentelevation acute coronary syndromes);
in addition, in the most recent surveys, some patients
with NSTEMI type 2 may not have been included, be-
cause they may have been hospitalized in regular wards
instead of intensive cardiac care units. In addition, be-
cause the population was recruited from cardiac inten-
sive care units, 2 types of populations are likely to be
underrepresented: first, patients with out-of-hospital
10 September 5, 2017
cardiac arrest, admitted to general intensive care units
instead of intensive cardiac care units, because of se-
verely compromised conditions after resuscitation; sec-
ond, very elderly individuals with AMI, who may have
been admitted to geriatric units or general wards. Fi-
nally, for the present analysis, because we wanted to
include the most recent survey performed at the end of
2015, only 6-month follow-up was available. Converse-
ly, all surveys can be considered highly representative of
the management and outcomes of patients hospital-
ized for AMI in France, with a high overall participation
rate, with all major institutions actually participating in
the surveys, and with the totality of the metropolitan
French territory covered. The size of each cohort is suf-
ficient to allow statistically reliable comparisons with a
good degree of precision, and the snapshot nature of
the different registries allows comprehensive data col-
lection and monitoring, without exhausting the investi-
gators. To our knowledge, this approach, on a country
scale, and setup as early as 1995 remains unique.
CONCLUSIONS
From 1995 to 2015, 6-month mortality of both patients
with STEMI and NSTEMI decreased considerably, to-
gether with major increases in the use of recommended
medications and procedures over time. In patients with
STEMI, mortality has continued to decrease since 2010,
to reach an all-time low in 2015. In patients with NSTE-
MI, despite recent changes in antithrombotic medica-
tions at the acute stage, mortality has remained similar
in 2015 in comparison with 2010. Prolonged follow-
up will determine whether improvement in survival will
persist or materialize in both types of patients.
ACKNOWLEDGMENTS
The authors are deeply indebted to all physicians who have
taken care of the patients at the participating institutions.
SOURCES OF FUNDING
The French Society of Cardiology received grants for support-
ing the FAST-MI program from Amgen, AstraZeneca, Bayer,
BMS, Boehringer-Ingelheim, Daiichi Sankyo, Eli Lilly, MSD,
Pfizer, and Sanofi.
DISCLOSURES
None.
AUTHORS
Etienne Puymirat, MD, PhD; Tabassome Simon, MD, PhD;
Guillaume Cayla, MD, PhD; Yves Cottin, MD, PhD; Meyer
Circulation. 2017;136:0000. DOI: 10.1161/CIRCULATIONAHA.117.030798

Elbaz, MD, PhD; Pierre Coste, MD, PhD; Gilles Lemesle, MD,
PhD; Pascal Motreff, MD, PhD; Batric Popovic, MD, PhD; Khal-
ife Khalife, MD; Jean-Noel Labque, MD; Thibaut Perret, MD;
Christophe Le Ray, MD; Laurent Orion, MD; Bernard Jouve,
MD; Didier Blanchard, MD; Patrick Peycher; Johanne Silvain,
MD, PhD; Philippe Gabriel Steg, MD, PhD; Patrick Goldstein,
MD; Pascal Guret, MD, PhD; Loic Belle, MD; Nadia Aissaoui,
MD, PhD; Jean Ferrires, MD, PhD; Franois Schiele, MD, PhD;
Nicolas Danchin,MD, PhD; for the USIK, USIC 2000, and FAST-
MI investigators
AFFILIATIONS
From Assistance Publique-Hpitaux de Paris (AP-HP), Hpital
Europen Georges Pompidou, Department of Cardiology;
Universit Paris-Descartes, Paris, France; INSERM U-970,
France (E.P., N.A., N.D.); AP-HP, Hpital Saint Antoine,
Department of Clinical Pharmacology and Unit de
Recherche Clinique (URCEST), Paris, France; Universit Pierre
Downloaded from http://circ.ahajournals.org/ by guest on August 27, 2017
et Marie Curie (UPMC-Paris 06); INSERM U-698, France
(T.S.); Centre Hospitalier Universitaire de Nmes, France
(G.C.); Centre Hospitalier Universitaire du Bocage, Dijon,
France (Y.C.); Toulouse University Hospital, Department
of Cardiology, France (M.E.); Hpital Cardiologique Haut
Levque, CHU de Bordeaux, Pessac, France (P.C.); Lille
Regional University Hospital, Department of Cardiology,
France (G.L.); Department of Cardiology, University Hospital
of Clermont-Ferrand, UMR 6284 Auvergne University,
France (P.M.); Dpartement de cardiologie, CHU de Nancy,
Vanduvre-ls-Nancy, France (B.P.); Centre Hospitalier
Rgional de Metz-Thionville, Mets, France (K.K.); Centre
Hospitalier de la Cte Basque, Bayonne, France (J.-N.L.);
Department of cardiology, Centre Hospitalier St Joseph
et St Luc, Lyon, France (T.P.); Centre Hospitalier Bretagne
Atlantique, Vannes, France (C.L.R.); Department of
cardiology, Centre Hospitalier de Vende, La Roche-sur-Yon,
France (L.O.); Hospital of Aix en Provence, Department of
Cardiology, France (B.J.); Clinique St Gatien, Tours, France
(D.B.); Clinique Axium Aix en Provence, France (P.P.); Institut
de Cardiologie, Centre Hospitalier Piti-Salptrire, Paris,
France (J.S.); AP-HP, Hpital Bichat, Paris, France; Universit
Paris-Diderot, Sorbonne Paris-Cit, France; INSERM U-698,
75018 Paris, France (P.G.S.); Lille Regional University
Hospital, Emergency Department, France (P. Goldstein);
University Hospital Henri Mondor, Department of Cardiology,
Crteil, France (P. Guret); Department of Cardiology, Centre
hospitalier Annecy Genevois, Epagny Metz-Tessy, France
(L.B.); Toulouse Rangueil University Hospital, Department of
Cardiology; UMR1027, INSERM, France (J.F.); and University
Hospital Jean Minjoz, Department of Cardiology, Besanon,
France (F.S.).
FOOTNOTES
Received July 28, 2017; accepted August 14, 2017.
The online-only Data Supplement is available with this article at
http://circ.ahajournals.org/lookup/suppl/doi:10.1161/
CIRCULATIONAHA.117.030798/-/DC1.
Circulation is available at http://circ.ahajournals.org.
Circulation. 2017;136:0000. DOI: 10.1161/CIRCULATIONAHA.117.030798
20-Year Trends in STEMI and NSTEMI
ORIGINAL RESEARCH
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Circulation. 2017;136:0000. DOI: 10.1161/CIRCULATIONAHA.117.030798
 Acute Myocardial Infarction: Changes in Patient Characteristics, Management, and
6-Month Outcomes Over a Period of 20 Years in the FAST-MI Program (French Registry
of Acute ST-Elevation or Non-ST-elevation Myocardial Infarction) 1995 to 2015
Etienne Puymirat, Tabassome Simon, Guillaume Cayla, Yves Cottin, Meyer Elbaz, Pierre Coste,
Gilles Lemesle, Pascal Motreff, Batric Popovic, Khalife Khalife, Jean Noel Labeque, Thibault
Perret, Christophe Le Ray, Laurent Orion, Bernard Jouve, Didier Blanchard, Patrick Peycher,
Johanne Silvain, P. Gabriel Steg, Patrick Goldstein, Pascal J. Gueret, Loic Belle, Nadia
Downloaded from http://circ.ahajournals.org/ by guest on August 27, 2017

Aissaoui, Jean Ferrires, Francois Schiele, Nicolas Danchin and For the USIK, USIC 2000, and
FAST-MI Investigators
For the USIK, USIC 2000, and FAST-MI Investigators

Circulation. published online August 27, 2017;

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SUPPLEMENTAL MATERIAL

Supplemental Methods 1. Methodology of the 5 surveys.

Supplemental Methods 2. Algorithm for treatments after acute myocardial infarction, based

upon the recent European guidelines.

Supplemental Table 1. Discharge medications in ST- and non-ST-elevation myocardial

infarction.

Supplemental Table 2. In-hospital evolution and complications of patients with ST-segment

elevation myocardial infarction from 1995 to 2015.

Supplemental Table 3. In-hospital evolution and complications of patients with non-ST-

segment elevation myocardial infarction from 1995 to 2015.

Supplemental Table 4. Adjusted hazard ratios (95% confidence interval) for six-month

mortality by year of survey. Several

Supplemental Table 5: Independent association between use of recommended medications

and interventional procedures at the acute stage and 6-month mortality.

Supplemental Figure 1. Reperfusion therapy in ST-elevation myocardial infarction and

percutaneous coronary intervention 72 hours from admission in non-ST-elevation

myocardial infarction.

Supplemental Figure 2. Trends in crude and standardized mortality (mortality figures in the

first 4 surveys standardized on baseline characteristics of 2015 population). A: STEMI

patients. B: NSTEMI patients.

1
Supplemental Methods 1. Methodology of the 5 surveys.

USIK 1995:

- Sponsor: Roussel

- Principal investigators: N. Danchin, JP Cambou

- The protocol was reviewed by the Committee for the Protection of Human Subjects in

Biomedical Research of Nancy University hospital (Nancy, France).

- Aim: To obtain detailed characteristics of patients admitted to an intensive care unit

for acute myocardial infarction (AMI) over a one-month period in France

- Institutions: voluntary participation of any institution authorised to take care of AMI

patients, i.e. university hospitals, general hospitals, private clinics, with or without

catheterization laboratory.

- Patient population: consecutive patients admitted to the participating centres and

meeting the following criteria:

o Inclusion criteria:

Diagnosis of AMI on the basis of elevated cardiac markers higher than

twice the upper limit of normal, in combination with:

Chest pain lasting for at least 30 minutes and not relieved by

nitrates

Or ECG changes on at least 2 contiguous leads with pathologic

new Q waves or ST elevation or depression >0.1 mV

Time from onset to admission < 48 hours

o Exclusion criteria:

Iatrogenic myocardial infarction

AMI diagnosis invalidated in favour of another diagnosis

- Period of inclusion: 1st-30th of November 1995

2
 - Paper case record form, filled-in by a physician responsible for the study at each site.

Classes of medications prescribed at different time-points were recorded.

- One-year follow-up done by the local investigator

USIK 2000:

- Sponsor: Aventis

- Principal investigators: N. Danchin, JP Cambou

- The protocol was reviewed by the Committee for the Protection of Human Subjects in

Biomedical Research of Nancy University hospital (Nancy, France).

- Aim: to gather complete and representative data on the management and outcome of

patients admitted to intensive care units for acute myocardial infarction (AMI) over a

one month period in France.

- Institutions: voluntary participation of any institution authorised to take care of AMI

patients, i.e. university hospitals, general hospitals, private clinics, with or without

catheterization laboratory.

- Patient population: consecutive patients admitted to the participating centres and

meeting the following criteria:

o Inclusion criteria:

Diagnosis of AMI on the basis of elevated cardiac markers higher than

twice the upper limit of normal, in combination with:

Chest pain lasting for at least 30 minutes and not relieved by

nitrates

Or ECG changes on at least 2 contiguous leads with pathologic

new Q waves or persisting ST elevation or depression >0.1 mV

3
 Time from onset to admission < 48 hours

o Exclusion criteria:

Iatrogenic myocardial infarction

AMI diagnosis invalidated in favour of another diagnosis

- Period of inclusion: 1st-30th of November 1995

- Paper case record form, filled-in by a physician responsible for the study at each site.

Classes of medications prescribed at different time-points were recorded.

- One-year follow-up done by the local investigator

FAST-MI 2005:

- Sponsor: French Society of Cardiology

- Principal investigators: N. Danchin, T. Simon

- Funding: Pfizer, Servier, and additional grant from the French National Health

Insurance (CNAM-TS).

- The protocol was reviewed by the Committee for the Protection of Human Subjects in

Biomedical Research of Saint Antoine University Hospital (Paris, France).

- Aim: to evaluate practices for AMI management in "real life" practice, and to measure

their impact on the medium- and long-term outcomes of patients admitted to intensive

care units for AMI over a one month period in France.

- Institutions: voluntary participation of any institution authorised to take care of AMI

patients, i.e. university hospitals, general hospitals, private clinics, with or without

catheterization laboratory.

- Patient population: consecutive adult patients admitted to the participating centres and

meeting the following criteria:

4
 o Inclusion criteria:

Diagnosis of AMI on the basis of elevated CK-MB or troponin, in

combination with:

Symptoms compatible with prolonged myocardial ischaemia

Or ECG changes compatible with myocardial ischaemia:

pathologic new Q waves or ST elevation, ST depression, or T

wave inversion

Time from onset to admission < 48 hours

Patients who died very early after admission and for whom cardiac

markers were not measured or not yet elevated were included if they

had compatible signs or symptoms associated with typical ST changes.

o Exclusion criteria:

Iatrogenic myocardial infarction

AMI diagnosis invalidated in favour of another diagnosis

- Period of inclusion: study start in the participating centres between October 1st and

November 15th 2005, inclusion for 31 consecutive days

- Electronic case record form with automated data queries, filled-in by dedicated

research technicians sent at each site at least once a week. Details (exact type and

dose) of all medications prescribed at different time-points. Blood collection (DNA

and serum) for core laboratory analysis, in the largest centres.

Ten-year follow-up centralised at the French Society of Cardiology, and done by dedicated

research technicians

5
FAST-MI 2010:

- Sponsor: French Society of Cardiology

- Principal investigators: N. Danchin, T. Simon

- Funding: MSD, the Daiichi-Sankyo/Eli-Lilly alliance, AstraZeneca, GSK, Novartis,

Sanofi.

- The protocol was reviewed and approved by the Committee for the Protection of

Human Subjects of Saint Louis University Hospital (Paris, France).

- Aim: to provide an extensive description of the population of patients admitted for

AMI throughout the French territory, to determine whether differences in terms of

population characteristics existed across regions, to assess the management of the

patients suffering from AMI, and to determine the implementation of practice

guidelines in a real world setting. Other objectives were to assess the correlations

between management strategies and outcomes, to determine the correlations between

genetic polymorphisms and morbi-mortality in relation with the effects of

medications, and to determine relationships between biomarkers and morbi-mortality.

Another objective was to enable historic comparisons with the previous French

registries.

- Institutions: voluntary participation of any institution authorised to take care of AMI

patients, i.e. university hospitals, general hospitals, private clinics, with or without

catheterization laboratory.

- Patient population: consecutive adult patients admitted to the participating centres and

meeting the following criteria:

o Inclusion criteria:

Diagnosis of acute myocardial infarction on the basis of elevated CK-

MB or troponin, in combination with:

6
 Symptoms compatible with prolonged myocardial ischaemia

Or ECG changes compatible with myocardial ischaemia:

pathologic new Q waves or ST elevation, ST depression, or T

wave inversion

Time from onset to admission < 48 hours

Patients who died very early after admission and for whom cardiac

markers were not measured or not yet elevated were included if they

had compatible signs or symptoms associated with typical ST changes.

o Exclusion criteria:

Iatrogenic myocardial infarction

AMI diagnosis invalidated in favour of another diagnosis

- Period of inclusion: study start in the participating centres between October 1st and

November 15th 2005, inclusion for 31 consecutive days

- Electronic case record form with automated data queries, filled-in by dedicated

research technicians sent at each site at least once a week. Details (exact type and

dose) of all medications prescribed at different time-points. Blood collection (DNA

and serum) for core laboratory analysis, in the largest centres.

- Ten-year follow-up centralised at the French Society of Cardiology, and done by

dedicated research technicians.

FAST-MI 2015:

- Sponsor: French Society of Cardiology

- Principal investigators: N. Danchin, T. Simon

- Funding: Amgen, AstraZeneca, Bayer, BMS, Boehringer-Ingelheim, the Daiichi-

Sankyo-Eli-Lilly alliance, MSD, Sanofi.

7
- The protocol was reviewed and approved by the Committee for the Protection of

Human Subjects of Saint Louis University Hospital Paris Ile de France IV (Paris,

France).

- Aim : to provide a precise and extensive description of the population of patients

admitted for AMI throughout the French metropolitan territory, and to determine

whether regional differences existed in terms of patient population; to assess the

management of the patients admitted to cardiology departments for AMI; to determine

the actual implementation of practice guidelines in a real world setting; to assess the

correlations between management strategies and in-hospital outcomes; to determine

the impact of several genetic polymorphisms on morbidity-mortality and their

interaction with the effect of medications; and, to determine the impact of biomarkers

on morbidity-mortality after MI.

- Institutions: a list of all intensive cardiac care units (ICCU) authorised to receive ACS

emergencies and admitting patients at the acute stage of MI was established at the

beginning of 2015, and participation in the study was offered to all types of

institutions (academic hospitals, general hospitals, army hospitals and private clinics).

In all, 261 centres were listed, 215 of which initially accepted to participate in the

study. Of those, 204 actively participated, and included at least one patient during the

one-month study period. Participation rate was 78% and the centres were distributed

across the whole country.

- Patient population: patients were recruited consecutively from ICCU/cardiology

departments over a period of one month (from October, 5th 2015). Recruitment could

be prolonged up to 2 months in the centres willing to do so. Inclusion and exclusion

criteria were similar to previous registries:

o Inclusion criteria:

8
 Diagnosis of acute myocardial infarction on the basis of elevated CK-

MB or troponin, in combination with:

Symptoms compatible with prolonged myocardial ischaemia

Or ECG changes compatible with myocardial ischaemia:

pathologic new Q waves or ST elevation, ST depression, or T

wave inversion

Time from onset to admission < 48 hours

Patients who died very early after admission and for whom cardiac

markers were not measured or not yet elevated were included if they

had compatible signs or symptoms associated with typical ST changes.

o Exclusion criteria:

Iatrogenic myocardial infarction

AMI diagnosis invalidated in favour of another diagnosis

- Period of inclusion: study start in the participating centres between October 1st and

November 15th 2015, inclusion for 31 consecutive days

- Electronic case record form with automated data queries, filled-in by dedicated

research technicians sent at each site at least once a week. Details (exact type and

dose) of all medications prescribed at different time-points. Blood collection (DNA

and serum) for core laboratory analysis, in the largest centres ; finally, some centres

also collected stools for the purpose of studying intestinal microbiote.

- Primary PCI in STEMI patients defined as time to admission < 12 hours from onset,

no fibrinolysis, and intended PCI within 24 hours of onset.

- Ten-year follow-up centralised at the French Society of Cardiology, and done by

dedicated research technicians.

9
Data file collection and storage were approved by the Commission Nationale

Informatique et Libert for all registries.

Acknowledgements

The authors are indebted to the patients who accepted to participate and to all physicians who

took care of them. We acknowledge the help of ICTA contract research organization

(Fontaine-ls-Dijon, France), and Axonal (Nanterre, France) for data collection. Our deep

gratitude to the devoted personnel of the URCEST (Assistance Publique des Hpitaux de

Paris and University Paris 6) and INSERM U 1027 (Toulouse). Special thanks to Vincent

Bataille, PhD, for his careful data management, to Benot Pace (Socit Franaise de

Cardiologie) for his invaluable assistance in designing the electronic CRF, and to Genevive

Mulak, Pharm D. and Nicole Naccache, Pharm D. (Socit Franaise de Cardiologie) for their

help in the conduct of the FAST-MI registries, and to Elodie Drouet, MSc, who supervised

patient follow-up.

10
Supplemental Methods 2. Algorithm for treatments after acute myocardial infarction, based

upon the recent European guidelines.

We applied an appropriateness algorithm for treatments, based upon the recent European

guidelines. Medical treatment was considered appropriate if antiplatelet agents and statins

were used for all patients, angiotensin-converting-enzyme inhibitors (ACE-I) in patients with

a history of heart failure, low ejection fraction (left ventricular ejection fraction, LVEF

<40%), Killip class >1 during the current episode, or history of diabetes or hypertension; and

beta-blockers in patients with a history of heart failure, LVEF <40%, Killip class >1 or

STEMI patients.

11
Supplemental Table 1: Coronary artery bypass graft, pace-maker, implantable cardioverter

defibrillator during hospital stay, and discharge medications in ST- and non-ST-elevation

myocardial infarction.

USIK USIC FAST-MI FAST-MI FAST-MI

P
STEMI 1995a 2000 2005 2010 2015
value
(n=1536) (n=1844) (n=1611) (n=1716) (n=1872)

CABG 10 (0.7)** 56 (3) 44 (3) 21 (1) 26 (1) 0.461

PM -- -- 10 (0.5) 8 (0.3) 8 (0.3) 0.242

ICD -- -- 3 (0.2) 4 (0.2) 18 (0.7) 0.002

Discharge
medications

Antiplatelet
-- 1597 (95) 1476 (97) 1624 (99) 1806 (99) <0.001
agents

Statin -- 1092 (65) 1308 (86) 1531 (93) 1726 (95) <0.001

Beta-blocking
-- 1299 (77) 1215 (80) 1461 (89) 1610 (88.5) <0.001
agents

ACE-I or ARB -- 898 (53) 1071 (71) 1374 (84) 1418 (78) <0.001

Appropriate
recommended -- 72 (43) 930 (61) 1276 (77.5) 1374 (76.5) <0.001
therapy

USIK USIC FAST-MI FAST-MI FAST-MI

NSTEMI 1995 a 2000 2005 2010 2015

(n=616) (n=476) (n=1448) (n=1363) (n=1941)

CABG 5 (0.8)** 23 (5) 74 (5) 69 (5) 84 (4) 0.015

PM -- -- 18 (1) 10 (0.6) 27 (1) 0.844

ICD -- -- 9 (0.5) 7 (0.4) 20 (0.7) 0.236

Discharge
medications

12
 Antiplatelet
-- 411 (93) 1299 (94) 1285 (97) 1796 (95) <0.001
agents

Statin -- 256 (58) 1084 (79) 1168 (88) 1671 (88) <0.001

Beta-blocking
-- 1348 (73) 1162 (72) 1384 (81) 1421 (75) <0.001
agents

ACE-I or ARB -- 197 (45) 880 (64) 987 (75) 1307 (69) <0.001

Appropriate
recommended -- 158 (36) 756 (55) 935 (70) 1278 (69) <0.001
therapy

a: discharge medications not recorded in 1995

**: CABG performed within 5 days of admission.

Abbreviations: ACE, angiotensin-converting enzyme inhibitors; ARB, angiotensin receptor

blockers; CABG: coronary artery bypass grafting; ICD: implantable cardioverter defibrillator;

NSTEMI, Non-ST-elevation myocardial infarction; PM: pace-maker; STEMI, ST-elevation

myocardial infarction

13
Supplemental Table 2. In-hospital evolution and complications of patients with ST-segment

elevation myocardial infarction from 1995 to 2015

USIK USIC FAST-MI FAST-MI FAST-MI P

1995a 2000a 2005 2010 2015 for

(n=1536) (n=1844) (n=1611) (n=1716) (n=1872) Trend

Duration of hospital
- 10.410.8 8.67.9 7.67.8 6.87.9 <0.001
stay (days)

LVEF 40% 267 (26) 276 (19) 282 (20) 333 (23) 339 (19) <0.001

Maximal Killip

class during stay:

- I 999 (65) 1300 (71) 1221 (76) 1383 (81) 1593 (85) <0.001

- II 308 (20) 281 (15) 192 (12) 178 (10) 99 (5)

- III 115 (7.5) 128 (15) 94 (6) 75 (4) 50 (3)

- IV 114 (7) 132 (7) 102 (6) 80 (5) 62 (3)

192
Occurrence of AF 142 (8) 99 (6) 96 (6) 99 (5) <0.001
(12.5)

Ventricular
65 (4) 68 (4) 49 (3) 47 (3) 56 (3) 0.10
fibrillation

New AV block 120 (8) 96 (5) 34 (2) 44 (3) 73 (4) <0.001

Recurrent MI - 47 (3) 23 (1) 18 (1) 6 (0.3) <0.001

Stroke - 19 (1) 16 (1) 12 (0.7) 10 (0.5) 0.28

Major bleeding - - 30 (2) 41 (2) 28 (1.5) 0.387

30-day mortality 210 (14) 178 (10) 111 (7) 75 (4) 64 (3) <0.001

Data are presented as n (%) or mean SD

14
Abbreviations: AF, atrial fibrillation; AV, atrio-ventricular; LVEF, left ventricular ejection

fraction; MI, myocardial infarction

a
For 1995 and 2000, blank cells indicate data not available

15
Supplemental Table 3. In-hospital evolution and complications of patients with non-ST-

segment elevation myocardial infarction from 1995 to 2015

USIK USIC FAST-MI FAST-MI FAST-MI P

1995a 2000a 2005 2010 2015 for

(n=616) (n=476) (n=1448) (n=1363) (n=1941) Trend

Duration of hospital
- 10.56.7 9.99.1 8.58.7 7.39.0 <0.001
stay (days)

LVEF 40% 80 (19) 64 (17) 248(22) 190 (17) 257 (15) 0.33

Maximal Killip

class during stay

- I
408 (66) 313 (66) 957 (67) 1052 (77) 1574 (81) <0.001
- II
124 (20) 69 (14.5) 216 (15) 153 (11) 128 (7)
- III
50 (8) 60 (13) 186 (13) 116 (8.5) 130 (7)
- IV
34 (5.5) 33 (7) 77 (5) 42 (3) 43 (2)

Atrial fibrillation 68 (11) 52 (11) 76 (5) 62 (4.5) 115 (6) <0.001

Ventricular
19 (3) 13 (3) 18 (1) 10 (1) 14 (1) <0.001
fibrillation

New AV block 24 (4) 11 (2) 17 (1) 18 (1) 46 (2) <0.001

Recurrent MI - 10 (2) 33 (2) 17 (1) 8 (0.4) <0.001

TIMI major
- - 37 (3) 30 (2) 40 (2) 0.345
bleeding

Stroke - 3 (0.6) 13 (0.9) 2 (0.1) 12 (0.6) 0.07

30-day mortality 67 (11) 38 (8) 84 (6) 43 (3) 64 (3) <0.001

16
Data are presented as n (%) or mean SD

Abbreviations: AF, atrial fibrillation; AV, atrio-ventricular; LVEF, left ventricular ejection

fraction; MI, myocardial infarction

a
For 1995 and 2000, blank cells indicate data not available

17
Supplemental Table 4. Adjusted hazard ratios (95% confidence interval) for six-month

mortality by year of survey.

USIK USIC FAST-MI FAST-MI FAST-MI

Model
1995 2000 2005 2010 2015

STEMI n=1536 n=1844 n=1611 n=1716 n=1872

Model 1: Baseline
0.76 (0.63- 0.56 (0.46- 0.45 (0.36- 0.32 (0.26-
characteristics, region, type of 1.00
0.91) 0.69) 0.56) 0.41)
institution

Model 2: 0.74 (0.62- 0.52 (0.43- 0.40 (0.31- 0.24 (0.19-

1.00
Model 1 + peak CK 0.89) 0.65) 0.50) 0.32)

Model 3: model 2 +
0.93 (0.77- 0.81 (0.63- 0.83 (0.63- 0.49 (0.36-
reperfusion therapy, 1.00
1.13) 1.03) 1.10) 0.68)
medications 48 hours

Model 4: model 3 in 3-day 0.97 (0.76- 1.11 (0.83- 1.07 (0.76- 0.67 (0.46-
1.00
survivors 1.24) 1.49) 1.50) 0.98)

Model 5: model 2 + time from 0.71 (0.58- 0.53 (0.43- 0.38 (0.30- 0.24 (0.18-
1.00
onset to admission 0.86) 0.66) 0.48) 0.31)

Model 6: model 3 + time from 0.88 (0.72- 0.87 (0.69- 0.74 (0.56- 0.52 (0.37-
1.00
onset to admission 1.06) 1.10) 0.97) 0.72)

NSTEMI n=1536 n=1844 n=1611 n=1716 n=1872

Model 1: baseline
0.92 (0.67- 0.66 (0.51- 0.40 (0.30- 0.40 (0.30-
characteristics, region, type of 1.00
1.26) 0.85) 0.54) 0.52)
institution

Model 2: model 1 + 0.94 (0.68- 0.76 (0.58- 0.48 (0.35- 0.46 (0.34-
1.00
peak CK 1.28) 1.00) 0.65) 0.63)

18
 Model 3: model 2 +
1.15 (0.83- 1.23 (0.91- 0.97 (0.69- 0.95 (0.66-
PCI 72 hours + medications 1.00
1.59) 1.66) 1.39) 1.36)
72 hours

Model 4: model 3 in 3-day 1.30 (0.90- 1.57 (1.13- 1.27 (0.87- 1.38 (0.94-
1.00
survivors 1.87) 2.18) 1.85) 2.03)

Abbreviations: NSTEMI, Non-ST-elevation myocardial infarction; STEMI, ST-elevation

myocardial infarction

19
Supplemental Table 5: Independent association between use of recommended
medications and interventional procedures at the acute stage and 6-month mortality.

Hazard ratio (95% confidence P value

interval)

STEMI

Reperfusion therapy
- None 1.00
- Fibrinolysis 0.68 (0.55-0.91) <0.001
- Primary PCI 0.76 (0.64-0.91) 0.002
Anticoagulants other than 0.54 (0.46-0.64) <0.001
unfractionated heparin

Appropriate use of recommended 0.31 (0.25-0.39) <0.001

medications

NSTEMI

PCI within 72 hours of admission 0.61 (0.49-0.76) <0.001

Anticoagulants other than 0.67 (0.56-0.80) <0.001

unfractionated heparin

Appropriate use of recommended 0.45 (0.36-0.56) <0.001

medications

Use of a stepwise Cox multivariate analysis, including baseline characteristics, type of

institution, region, highest CK value, use of reperfusion therapy or percutaneous coronary

intervention, use of newer parenteral anticoagulants, and appropriate use of recommended

therapy during the first 48 hours.

20
Supplemental Figure 1. Reperfusion therapy in ST-elevation myocardial infarction and

percutaneous coronary intervention 72 hours from admission in non-ST-elevation

myocardial infarction.

21
Supplemental Figure2: Trends in crude and standardized mortality (mortality figures in the

first 4 surveys standardized on baseline characteristics of 2015 population). A: STEMI

patients. B: NSTEMI patients

22