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.

1

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.

2

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.

3

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

4

- 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:

5

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:

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

7

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

8

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.

9

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.

10

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

11

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

12

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

13

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

14

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

15

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.

16

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

17

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

18

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

19

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

20