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Transcript of €¦ · Web viewOnline-only material. eMethods. 1.
ONLINE-ONLY MATERIAL
eMethods 1. Methodology of the 4 surveys.
eMethods 2. Algorithm for treatments after acute myocardial infarction, based upon the recent
European guidelines.
eTable 1. Baseline characteristics of elderly patients with ST-elevation myocardial infarction from
1995 to 2010
eTable 2. Baseline characteristics of elderly patients with non-ST-elevation myocardial infarction
from 1995 to 2010
eTable 3. Baseline characteristics of elderly patients with acute myocardial infarction managed
without coronary angiogram from 2000 to 2010.
eTable 4. In-hospital evolution and complications of elderly patients with acute myocardial infarction
from 1995 to 2010.
eTable 5. Association between early management and one-year mortality in each survey
eTable 6. Association between early management and one-year mortality according to type of
myocardial infarction.
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eFigure 1. Evolution of initial management from 1995 to 2010 in elderly patients.
eFigure 2. 30-Day and one-year mortality in elderly patients with AMI according age class.
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eFigure 3. Evolution of 30-Day mortality from 1995 to 2010 according to early management in elderly
patients.
eFigure 4. One-year mortality in STEMI and NSTEMI patients by registry.
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eMethods 1. Methodology of the 4 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
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- 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
Time from onset to admission < 48 hours
o Exclusion criteria:
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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:
o Inclusion criteria:
Diagnosis of AMI on the basis of elevated CK-MB or troponin, in combination
with:
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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
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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:
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
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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.
Data file collection and storage were approved by the Commission Nationale Informatique et
Liberté for all registries.
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eMethods 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.15,16 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.
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eTable 1. Baseline characteristics of elderly patients with ST-elevation myocardial infarction from
1995 to 2010
USIK 1995a
(n=459)
USIC 2000
(n=514)
FAST-MI 2005
(n=445)
FAST-MI 2010
(n=437)P for Trend
Demographic, organisational and clinical Characteristics
Age (years) mean ± SD 82.0±5.1 81.7±5.1 82.0±5.0 82.4±5.1 0.19
Female, n (%) 232 (50.5) 247 (48.1) 230 (51.7) 198 (45.3) 0.23
BMI (Kg/m²) 24.6±3.8 25.1±3.8 25.7±4.4 25.6±4.1 <0.001
Risk factors, n (%)
Hypertension 256 (55.8) 304 (59.1) 311 (69.9) 322 (73.7) <0.001
Hypercholesterolemia 121 (26.4) 158 (30.7) 178 (40.0) 170 (38.9) <0.001
Diabetes mellitus 86 (19.0) 120 (23.3) 116 (26.1) 115 (26.3) 0.04
Current smoking 43 (9.4) 35 (6.8) 40 (9.0) 27 (6.2) 0.17
Obesity (BMI ≥30) 35 (8.2) 44 (9.9) 48 (13.3) 49 (12.5) 0.04
Cardiovascular history, n (%)
Myocardial Infarction 78 (17.0) 100 (19.5) 63 (14.2) 69 (15.8) 0.16
PCI - 22 (4.3) 43 (9.7) 57 (13.0) <0.001
CABG - 15 (2.9) 14 (3.1) 22 (5.0) 0.18
Stroke or TIA 47 (10.2) 39 (7.6) 44 (9.9) 39 (8.9) 0.47
Heart failure 61 (13.3) 57 (11.1) 43 (9.7) 28 (6.4) 0.006
PAD 62 (13.5) 53 (10.3) 37 (8.3) 35 (8.0) 0.02
Comorbidity, n (%)
CKD - 40 (7.8) 30 (6.7) 21 (4.8) 0.17
Medications before, n (%)
Antiplatelet therapy - 141 (27.4) 147 (33.0) 149 (34.1) 0.06
Statin - 73 (14.2) 95 (21.3) 111 (25.4) <0.001
ß−Blocker - 98 (19.1) 111 (24.9) 124 (28.4) 0.003
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ACE-I or ARB - 135 (26.3) 156 (35.0) 194 (44.4) <0.001
Diuretics - 138 (26.8) 140 (31.5) 158 (36.2) 0.008
ACE-I : angiotensin-converting-enzyme inhibitor; ARB: angiotensin receptor blocker; BMI: body mass index;
CABG: coronary artery bypass graft surgery; CKD: chronic kidney disease; PAD: peripheral artery disease; PCI:
percutaneous coronary intervention; TIA: transient ischemic attack.
a For 1995, blank cells indicate data not available
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eTable 2. Baseline characteristics of elderly patients with non-ST-elevation myocardial infarction
from 1995 to 2010
USIK 1995a
(n=224)
USIC 2000
(n=170)
FAST-MI 2005
(n=617)
FAST-MI 2010
(n=523)P for Trend
Demographic, organisational and clinical Characteristics
Age (years) mean ± SD 82.4± 5.6 82.2±5.3 82.3±5.1 82.2±4.6 0.19
Female, n (%) 119 (53.1) 76 (44.7) 304 (49.3) 234 (44.7) 0.13
BMI (Kg/m²) 25.0±4.0 25.7±4.3 25.8±4.4 26.0±4.5 <0.001
Risk factors, n (%)
Hypertension 136 (60.7) 118 (69.4) 482 (78.1) 401 (76.7) <0.001
Hypercholesterolemia 62 (27.7) 68 (40.0) 293 (47.5) 244 (46.7) <0.001
Diabetes mellitus 52 (23.5) 42 (24.7) 179 (29.0) 171 (32.7) 0.04
Current smoking 13 (5.8) 8 (4.7) 47 (7.6) 29 (5.5) 0.39
Obesity (BMI ≥30) 21 (10.4) 16 (11.3) 82 (15.6) 82 (17.3) 0.07
Cardiovascular history, n (%)
Myocardial Infarction 67 (29.9) 59 (34.7) 164 (26.6) 149 (28.5) 0.21
PCI - 26 (15.3) 104 (16.9) 133 (25.4) <0.001
CABG - 16 (9.4) 62 (10.0) 50 (9.6) 0.95
Stroke or TIA 22 (9.8) 20 (11.8) 85 (13.8) 48 (9.2) 0.09
Heart failure 69 (30.8) 38 (22.4) 77 (12.5) 64 (12.2) <0.001
PAD 38 (17.0) 29 (17.1) 114 (18.5) 91 (17.4) 0.94
Comorbidity, n (%)
CKD - 23 (13.5) 71 (11.5) 50 (9.6) 0.30
Medications before, n (%)
Antiplatelet therapy - 91 (53.5) 329 (53.3) 265 (50.7) 0.63
Statin - 38 (22.4) 202 (32.7) 212 (40.5) <0.001
ß−Blocker - 49 (28.8) 202 (32.7) 197 (37.7) 0.06
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ACE-I or ARB - 53 (31.5) 315 (51.1) 271 (51.5) <0.001
Diuretics - 67 (39.4) 289 (46.8) 225 (43.0) 0.17
ACE-I : angiotensin-converting-enzyme inhibitor; ARB: angiotensin receptor blocker; BMI: body mass index;
CABG: coronary artery bypass graft surgery; CKD: chronic kidney disease; PAD: peripheral artery disease; PCI:
percutaneous coronary intervention; TIA: transient ischemic attack.
a For 1995, blank cells indicate data not available
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eTable 3. Baseline characteristics of elderly patients with acute myocardial infarction managed
without coronary angiogram from 2000 to 2010.
USIC 2000
(n=312)
FAST-MI 2005
(n=372)
FAST-MI 2010
(n=162)P for Trend
Age (years) mean ± SD 84.2±5.4 85.3±5.4 85.7±5.0 0.002
Age ≥ 85 years, n (%) 151 (48.4) 194 (52.2) 92 (56.8) <0.001
Female, n (%) 167 (53.5) 217 (58.3) 84 (51.9) 0.28
BMI (kg/m²) mean ± SD 24.5±3.8 24.8±4.5 25.2±4.5 0.28
Risk factors, n (%)
Hypertension 212 (67.9) 284 (76.3) 132 (81.5) 0.003
Hypercholesterolemia 80 (25.6) 143 (38.4) 66 (40.7) <0.001
Diabetes mellitus 78 (25.0) 105 (28.2) 60 (37.0) 0.002
Current smoking 17 (5.4) 22 (5.9) 7 (4.3) 0.11
Cardiovascular history, n (%)
Myocardial Infarction 77 (24.7) 97 (26.1) 58 (35.8) 0.03
PCI 14 (4.5) 38 (10.2) 34 (21.0) <0.001
CABG 13 (4.2) 24 (6.5) 3 (1.9) 0.06
Stroke or TIA 37 (11.9) 60 (16.1) 19 (11.7) 0.19
Heart failure 60 (19.2) 67 (18.0) 31 (19.1) 0.41
PAD 42 (13.5) 71 (19.1) 34 (21.0) 0.05
Comorbidity, n (%)
CKD 46 (14.7) 56 (15.1) 33 (20.4) 0.15
Medications before, n (%)
Antiplatelet therapy 109 (34.9) 200 (53.8) 88 (54.3) <0.001
Statin 41 (13.1) 88 (23.7) 53 (32.7) <0.001
ß−Blocker 63 (20.2) 96 (25.8) 60 (37.0) <0.001
ACE-I or ARB 91 (29.1) 168 (45.2) 71 (43.8) <0.001
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Diuretics 106 (34.0) 172 (46.2) 81 (50.0) 0.001
ACE-I : angiotensin-converting-enzyme inhibitor; ARB: angiotensin receptor blocker; BMI: body mass index;
CABG: coronary artery bypass graft surgery; CKD: chronic kidney disease; PAD: peripheral artery disease; PCI:
percutaneous coronary intervention; TIA: transient ischemic attack.
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eTable 4. In-hospital evolution and complications of elderly patients with acute myocardial infarction
from 1995 to 2010.
USIK 1995a
(n=683)
USIC 2000a
(n=684)
FAST-MI 2005
(n=1062)
FAST-MI 2010
(n=960)
P for
Trend
In-hospital evolution and complications, n (%)
LVEF ≤ 40% 119 (33.0) 125 (27.9) 239 (29.9) 225 (27.7) 0.28
Maximal Killip class
during stay
- I
- II
- III
- IV
308 (45.1)
201 (29.4)
95 (13.9)
79 (11.6)
340 (49.7)
159 (23.2)
92 (13.5)
93 (13.6)
576 (54.6)
210 (19.9)
170 (16.1)
99 (9.4)
614 (64.0)
173 (18.0)
109 (11.4)
64 (6.7)
<0.001
Atrial fibrillation 147 (21.5) 113 (16.8) 101 (9.5) 97 (10.1) <0.001
Ventricular
fibrillation30 (4.4) 33 (4.9) 21 (2.0) 18 (1.9) <0.001
New AV block 78 (11.4) 45 (6.6) 23 (2.2) 36 (3.8) <0.001
Recurrent MI - 20 (2.9) 26 (2.4) 17 (1.8) 0.29
Reported major
bleeding- - 39 (3.7) 9 (0.9) <0.001
Stroke - 11 (1.6) 15 (1.4) 5 (0.5) 0.07
30-day mortality 171 (25.0) 115 (16.8) 138 (13.0) 81 (8.4) <0.001
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1-year mortality 247 (36.2) 205 (30.0) 286 (26.9) 192 (20.0) <0.001
AV: atrio-ventricular; LVEF: left ventricular ejection fraction; MI: myocardial infarction.
a For 1995 and 2000, blank cells indicate data not available
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eTable 5. Association between early management and one-year mortality in each survey.
Hazard
ratio
95% confidence
interval
P value
PCI in first 72 hours
- 1995
- 2000
- 2005
- 2010
0.77
0.72
0.51
0.43
0.36-1.65
0.47-1.10
0.37-0.70
0.29-0.64
0.50
0.13
<0.001
<0.001
Appropriate medical therapy
- 1995
- 2000
- 2005
- 2010
0.68
0.27
0.59
0.61
0.21-2.19
0.11-0.66
0.42-0.83
0.41-0.90
0.51
0.004
0.002
0.01
Newer anticoagulants
- 1995
- 2000
- 2005
- 2010
--
0.66
0.65
0.48
--
0.47-0.93
0.50-0.84
0.33-0.68
--
0.02
0.001
<0.001
PCI: percutaneous coronary intervention
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eTable 6. Association between early management and one-year mortality according to type of
myocardial infarction.
Hazard
ratio
95% confidence
interval
PCI in first 72 hours
- STEMI
- NSTEMI
0.55
0.60
0.43-0.70
0.43-0.85
Appropriate medical therapy
- STEMI
- NSTEMI
0.54
0.60
0.39-0.75
0.43-0.84
Newer anticoagulants
- STEMI
- NSTEMI
0.59
0.73
0.47-0.74
0.57-0.93
NSTEMI, non-ST-elevation myocardial infarction; PCI: percutaneous coronary intervention STEMI, ST-elevation
myocardial infarction
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