ONLINE-ONLY MATERIAL

eMethods 1. Methodology of the 5 surveys.

eMethods 2. Algorithm for treatments after acute myocardial infarction, based upon the recent

European guidelines.

eTable1. Reperfusion therapy used according to gender.

eTable 2. In-hospital evolution and complications of patients with ST-segment elevation myocardial

infarction treated with reperfusion therapy from 1995 to 2015.

eTable 3. In-hospital evolution and complications of patients with ST-segment elevation myocardial

infarction treated without reperfusion from 1995 to 2015.

eTable 4. Independent association between year of the survey and one-year mortality in patients

with or without reperfusion therapy.

eFigure 1. Trends in thirty-day mortality according to use and type of reperfusion therapy

1

eMethods 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

Time from onset to admission < 48 hours

o Exclusion criteria:

3

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:

4

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:

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

6

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.

- 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

7

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:

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

8

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.

- 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.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%, or Killip class >1.

10

eTable 1. Reperfusion therapy used according to gender.

1995 2000 2005 2010 2015

Reperfusion therapy used in male, n (%)

617 (55.8%) 757 (56.3%) 789 (68.4%) 1037 (80.2%) 1061 (75.6%)

Reperfusion therapy used in female, n (%)

142 (32.9%) 217 (43.5%) 249 (54.4%) 295 (69.7%) 303 (64.6%)

11

eTable 2. In-hospital evolution and complications of patients with ST-segment elevation myocardial

infarction treated with reperfusion therapy from 1995 to 2015.

USIK

1995a

(n=759)

USIC

2000a

(n=974)

FAST-

MI

2005

(n=1038)

FAST-MI 2010

(n=1332)

FAST-MI

2015

(n=1364)

P

for Trend

Duration of hospital stay (days) - 10.0±13.3 8.0±7.3 7.2±7.7 6.4±7.7 <0.001

LVEF ≤ 40% 139 (25) 131 (16.5) 170 (19) 232 (21) 238 (18.5) 0.002

Maximal Killip class during stay:

- I

- II

- III

- IV

552 (73)

128 (17)

34 (4.5)

45 (6)

734 (76)

133 (14)

45 (5)

59 (6)

834 (80)

99 (9.5)

41 (4)

63 (6)

1106 (83)

127 (9.5)

43 (3)

56 (4)

1179 (86)

63 (5)

30 (2)

43 (3)

<0.001

Occurence of AF 61 (8) 62 (6) 59 (6) 69 (5) 69 (5) 0.04

Ventricular fibrillation 36 (5) 45 (5) 39 (4) 41 (3) 48 (3.5) 0.20

New AV block 49 (6.5) 46 (5) 21 (2) 29 (2) 58 (4) <0.001

Recurrent MI - 21 (2) 14 (1) 16 (1) 2 (0.1) <0.001

Stroke - 8 (0.8) 9 (0.9) 10 (0.8) 8 (0.6) 0.86

Major bleeding - - 20 (2) 12 (1) 4 (0.3) <0.001

30-day mortality 63 (8) 69 (7) 49 (5) 39 (3) 43 (3) <0.001

6-month mortality 82 (11) 87 (9) 65 (6) 63 (5) 65 (5) <0.001

1-year mortality 90 (12) 94 (10) 73 (7) 78 (6) 80 (6) <0.001

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

12

13

eTable 3. In-hospital evolution and complications of patients with ST-segment elevation myocardial

infarction treated without reperfusion from 1995 to 2015.

USIK

1995a

(n=777)

USIC

2000a

(n=870)

FAST-MI

2005

(n=573)

FAST-MI 2010

(n=384)

FAST-MI

2015

(n=508)

P

for Trend

Duration of hospital stay (days) - 10.8±6.7 9.8±8.7 9.0±8.0 7.6±8.4 <0.001

LVEF ≤ 40% 129 (27) 145 (21) 112 (24) 101 (29) 101 (21) 0.01

Maximal Killip class during stay:

- I

- II

- III

- IV

447 (57.5)

180 (23)

81 (10)

69 (9)

566 (65)

148 (17)

83 (9.5)

73 (8)

387 (68)

93 (16)

53 (9)

39 (7)

277 (72)

51 (13)

32 (8)

24 (6)

414 (81.5)

36 (7)

20 (4)

19 (4)

<0.001

Occurence of AF 131 (17) 80 (9) 40 (7) 27 (7) 30 (6) <0.001

Ventricular fibrillation 29 (4) 23 (3) 10 (2) 6 (2) 8 (2) 0.048

New AV block 71 (9) 50 (6) 13 (2) 15 (4) 15 (3) <0.001

Recurrent MI - 26 (3) 9 (2) 2 (0.5) 4 (0.8) 0.003

Stroke - 11 (1) 7 (1) 2 (0.5) 2 (0.4) 0.28

Major bleeding - - 10 (2) 2 (0.5) 0 (0) 0.005

30-day mortality 147 (19)109

(12.5)62 (11) 36 (9)

21 (5)<0.001

6-month mortality 182 (23) 147 (17) 91 (16) 56 (15) 34 (7) <0.001

1-year mortality 194 (25) 168 (19) 110 (19) 70 (19) 41 (9) <0.001

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

14

15

eTable 4. Independent association between year of the survey and one-year mortality in patients

with or without reperfusion therapy.

Patients with reperfusion therapy Model 1 : adjusted for baseline

characteristics

Adjusted HR, 95% CI (reference

1995) :

- 2000 : 0.82 (0.61-1.09)

- 2005 : 0.53 (0.39-0.73)

- 2010 : 0.42 (0.31-0.56)

- 2015 : 0.40 (0.29-0.54)

Model 2 : adjusted for baseline

characteristics and management in

first 48 hours

Adjusted HR, 95% CI (reference

1995) :

- 2000 : 1.03 (0.77-1.39)

- 2005 : 0.98 (0.70-1.36)

- 2010 : 0.95 (0.68-1.34)

- 2015 : 0.96 (0.67-1.36)

Patients without reperfusion

therapy

Model 1 : adjusted for baseline

characteristics

Adjusted HR, 95% CI (reference

1995) :

- 2000 : 0.78 (0.64-0.96)

- 2005 : 0.71 (0.56-0.90)

- 2010 : 0.68 (0.52-0.90)

- 2015 : 0.33 (0.24-0.47)

Model 2 : adjusted for baseline

characteristics and management in

Adjusted HR, 95% CI (reference

16

first 48 hours 1995) :

- 2000 : 0.97 (0.78-1.20)

- 2005 : 1.13 (0.86-1.44)

- 2010 : 1.24 (0.91-1.69)

- 2015 : 0.63 (0.44-0.92)

CI, confidence interval; HR, Hazard ratio

17

eFigure 1. Trends in thirty-day mortality according to use and type of reperfusion therapy

18