Conclusions Certain emergency firefighting duties were associated with a risk of death from coronary heart disease that was markedly higher than the risk associated with nonemergency dut
Trang 1The new england
Emergency Duties and Deaths from Heart Disease
among Firefighters in the United States
Stefanos N Kales, M.D., M.P.H., Elpidoforos S Soteriades, M.D., Sc.D., Costas A Christophi, Ph.D.,
and David C Christiani, M.D., M.P.H
ABS TR ACT
From the Cambridge Health Alliance, Harvard Medical School, Cambridge, MA (S.N.K.); the Department of Environmen tal Health, Harvard School of Public Health, Boston (S.N.K., E.S.S., D.C.C.); the Pulmonary and Critical Care Unit, Massachusetts General Hospital, Boston (D.C.C.); the Center for Occupational and Environmental Medicine, Kindred Hos pital Northeast, Braintree, MA (D.C.C.); and the Cyprus International Institute for the Environment and Public Health in association with the Harvard School of Public Health, Nicosia, Cyprus (C.A.C.) Address reprint requests to Dr Kales at the Cambridge Health Alliance, Employee Health and Industrial Medicine, Lee B Macht Bldg., Rm 427, 1493 Cambridge St., Cambridge, MA 02139, or at skales@ challiance.org.
N Engl J Med 2007;356:120715.
Copyright © 2007 Massachusetts Medical Society.
Background
Heart disease causes 45% of the deaths that occur among U.S firefighters while
they are on duty We examined duty-specific risks of death from coronary heart
disease among on-duty U.S firefighters from 1994 to 2004
Methods
We reviewed summaries provided by the Federal Emergency Management Agency
of the deaths of all on-duty firefighters between 1994 and 2004, except for deaths
associated with the September 11, 2001, terrorist attacks Estimates of the
propor-tions of time spent by firefighters each year performing various duties were obtained
from a municipal fire department, from 17 large metropolitan fire departments, and
from a national database Odds ratios and 95% confidence intervals for death from
coronary heart disease during specific duties were calculated from the ratios of the
observed odds to the expected odds, with nonemergency duties as the reference
cat-egory
Results
Deaths from coronary heart disease were associated with suppressing a fire (32.1%
of all such deaths), responding to an alarm (13.4%), returning from an alarm
(17.4%), engaging in physical training (12.5%), responding to nonfire emergencies
(9.4%), and performing nonemergency duties (15.4%) As compared with the odds
of death from coronary heart disease during nonemergency duties, the odds were
12.1 to 136 times as high during fire suppression, 2.8 to 14.1 times as high during
alarm response, 2.2 to 10.5 times as high during alarm return, and 2.9 to 6.6 times
as high during physical training These odds were based on three estimates of the
time that firefighters spend on their duties
Conclusions
Certain emergency firefighting duties were associated with a risk of death from
coronary heart disease that was markedly higher than the risk associated with
nonemergency duties Fire suppression was associated with the highest risk, which
was approximately 10 to 100 times as high as that for nonemergency duties
Trang 2Firefighting is known to be a
dan-gerous occupation What is less appreciated
is that the most frequent cause of death among firefighters is heart disease rather than burns or smoke inhalation Cardiovascular events, largely due to coronary heart disease, account for 45% of deaths among firefighters on duty.1,2 In contrast, such events account for 22% of deaths among police officers on duty, 11% of deaths among on-duty emergency medical services work-ers, and 15% of all deaths that occur on the job.2,3The high rate of death from cardiovascular causes among firefighters raises questions about contrib-uting factors Possible factors, such as physical ex-ertion, emergency responses, and dangerous du-ties, are not unique to firefighting; they are also characteristic of the work performed by police of-ficers, military personnel, and persons in various other occupations.4,5
Various biologically plausible explanations for the high mortality from cardiovascular events among firefighters have been proposed These explanations include smoke and chemical expo-sure, irregular physical exertion, the handling of heavy equipment and materials, heat stress, shift work, a high prevalence of cardiovascular risk fac-tors, and psychological stressors.6-13 Given these occupational risks, 37 U.S states and 2 Canadian provinces provide benefits to firefighters in whom certain cardiovascular diseases have developed.14Nevertheless, the evidence linking firefighting
to cardiovascular disease continues to be
debat-ed.15-17 Therefore, whether deaths from coronary heart disease among firefighters are truly precipi-tated by their work and, if so, by which duties, remain important questions
The findings in our previous case–control study of 52 deaths from coronary heart disease among on-duty firefighters provided preliminary evidence that coronary events may be triggered by specific firefighting duties.18 First, the circadian pattern of deaths from coronary heart disease par-alleled the pattern of emergency-response dis-patches Second, elevated risks of death were as-sociated with fire suppression, alarm response, and physical training To confirm these findings and further explore duty-specific risk factors for death from coronary heart disease, we conducted
a study of all deaths that occurred among on-duty firefighters in the United States between 1994 and 2004
Methods
Deaths among Firefighters
The U.S Fire Administration, a branch of the Federal Emergency Management Agency, collects narrative summaries for all reported deaths as-sociated with firefighting in the United States From these publicly available summaries, we ex-amined data on all deaths that occurred between January 1, 1994, and December 31, 2004.2,19 The data included all firefighters who died while on duty, who became ill while on duty and later died, and who died within 24 hours after an emergency response or training We excluded deaths that oc-curred during the first 48 hours after the Septem-ber 11, 2001, terrorist attacks
To extract study data, two reviewers dently examined the summary of each reported death that occurred while the firefighter was on duty A third reviewer resolved any classifications that were not concordant between the first two reviewers On the basis of the narrative reports, each death was classified as due to cardiovascular causes or to noncardiovascular causes We then excluded those cases in which death occurred more than 24 hours after the on-duty incident or
indepen-in which death resulted from a cardiovascular problem other than coronary heart disease (e.g., certain arrhythmias, stroke, aneurysm, or genetic cardiomyopathy)
All records of deaths that were classified by this process as being due to coronary heart dis-ease were selected for further study Data extract-
ed from these records included the firefighter’s age, sex, and job status (professional or volun-teer); the date, cause, and mechanism of death; and the city and state of the fire department
Duties at the Time of Death
On the basis of the summary report of each death, the deaths were classified according to the spe-cific duty performed during the onset of symp-toms or immediately preceding sudden death These categories were fire suppression; alarm re-sponse; alarm return; physical training; emergen-
cy medical services, rescues, and other nonfire emergencies; and nonemergency duties A death was classified as being associated with fire sup-pression if it occurred while the person was fight-ing a fire or at the scene of a fire after its sup-pression Alarm response involved responses to
Trang 3emergency incidents, including false alarms Alarm
return included all events that occurred during
the return from incidents and those that occurred
within several hours after an emergency call
Physical training included all job-related
physical-fitness activities, physical-abilities testing, and
simulated or live fire, rescue, emergency, and
search drills We grouped together emergency
medical services, rescues, and other nonfire
emer-gencies in a separate category Finally, we
classi-fied all of the following activities as
nonemergen-cy duties: administrative and fire-station tasks,
fire prevention, inspection, maintenance,
meet-ings, parades, and classroom activities
Time Spent on Specific Duties
We used data from several sources to estimate
the average annual proportion of time that
fire-fighters spend in each category First, we
direct-ly derived point estimates from a municipal fire
department (Cambridge Fire Department,
Cam-bridge, MA), using fiscal year 2002 data, as in our
previous study.18 For Cambridge firefighters, the
following information was available: the number
of firefighters, the total number of alarms and
emergency responses, the distribution of
emer-gency calls and dispatches by hour of the day, a
breakdown of the types of incidents involved in
fire and nonfire emergency responses, the average
time spent per incident and the average response
time, and the estimated number of hours spent
each week in training and fire-prevention activities
We refer to these data as the municipal estimate
Second, to conduct a sensitivity analysis, we
obtained two additional sets of estimates, one
representing a level of emergency activity that was
higher than that of the Cambridge Fire
Depart-ment and the other representing a lower level of
emergency activity These estimates were derived
with the use of data for the population served,
the numbers of uniformed officers, and the
num-ber of emergency incidents and the types of
inci-dents classified as fire and nonfire emergencies
To characterize the largest and busiest fire
de-partments, an estimate was developed from 2005
survey data provided by the International
Associa-tion of Fire Fighters (Moore-Merrell L: personal
communication) for 17 large urban and suburban
fire departments (the large metropolitan
esti-mate) To represent firefighters in smaller
com-munities with lower levels of emergency activity,
an estimate was developed from nationwide tional Fire Protection Association surveys conduct-
Na-ed from 1994 to 2003 (the national estimate).20
Using the chi-square goodness-of-fit test, we assessed whether the distribution of actual deaths associated with each duty was the same as that
of expected deaths, based on the estimates of the average time dedicated to each firefighting duty
We used the three different time estimates (from the municipal, large metropolitan, and national data) to calculate the ratios of actual to expected deaths for each firefighting duty The 95% confi-dence intervals (CIs) for these ratios were calcu-lated on the basis of the multinomial distribu-tion Odds ratios for death from coronary heart disease during specific duties were calculated from the ratios of the observed to expected odds, with nonemergency duties used as the reference category The 95% CIs for the estimated odds ratios were calculated with the use of the bino-mial distribution
Using data from the 2000 firefighters census,21which stratifies firefighters according to their age (in decades) and job status (professionals or vol-unteers), we calculated the rates of death from coronary heart disease for specific duties accord-ing to age and job status Our calculations were based on death counts in each category per 1 mil-lion person-years of risk, derived from the average number of firefighters at risk in each subgroup over the 11-year period of observation
Analyses were performed with the use of SAS software for Windows (version 8.02, SAS Insti-tute), and StatXact (version 6.0) A P value of less than 0.05 was considered to indicate statistical significance, and all statistical tests for differ-ences were two-sided
Trang 4R esultsBetween January 1, 1994, and December 31, 2004,
1144 firefighter deaths were reported to the U.S
Fire Administration We classified 449 deaths as due to coronary heart disease (39%) Of these deaths from coronary heart disease, 144 (32%) occurred during fire suppression, 138 (31%) oc-curred during alarm response or return, and the remaining 167 (37%) occurred during other duties (Table 1)
Table 2 shows the estimated proportion of time that firefighters spent each year in specific duties according to the three sources of fire-department activity data that we used Among firefighters in Cambridge (our municipal data set), approximately 2% of duty time was spent in fire suppression Among firefighters in our large metropolitan data set, approximately 5% of duty time was spent in fire suppression Finally, among all firefighters in the United States (as represent-
ed in our national data set), approximately 1% of duty time was spent in fire suppression
Table 3 shows the frequency of observed deaths from coronary heart disease according to duty as compared with the expected frequency The ob-served distribution of deaths was significantly dif-ferent from the expected distribution based on the estimates from each of the three data sources (P< 0.001 for the three comparisons) The ratios of ob-served to expected deaths associated with the vari-ous duties of firefighters were consistently higher than 1, with the exception of nonfire emergencies and nonemergency duties Although 32% of deaths occurred during fire suppression, this activity was estimated to account for as little as 1 to 5% of the average firefighter’s professional time per year, so this duty was associated with the most significant-
ly elevated ratios of observed to expected deaths
According to Duty at the Time of Death.*
Emergency medical services and other nonfire emergencies 42 (9.4)
Firestation and other nonemergency duties 69 (15.4)
* Data are based on narrative summaries from the records of the U.S Fire Ad
ministration, Federal Emergency Management Agency, for the period from
January 1, 1994, to December 31, 2004 19
Table 2 Fire Service Activity and the Estimated Proportion of Time Spent in Specific Firefighting Duties.*
Fire service activity
Duties (% of annual time)
for large metropolitan fire departments are from surveys of 17 large metropolitan fire departments conducted by the International Associ ation of Fire Fighters (2005) (MooreMerrell L: personal communication) National data are from annual national surveys conducted by the National Fire Protection Association (1994 through 2003) 20
Trang 5Table 4 includes the odds ratios and 95% CIs
for the risk of death from coronary heart disease
among firefighters engaged in each emergency
duty and physical training as compared with the
reference category of nonemergency tasks On the
basis of the three estimates of the time that
fire-fighters spent on particular duties, death from
coronary heart disease was 12 to 136 times as
likely to occur during fire suppression as during
nonemergency duties An increased risk was also
consistently observed for other emergency duties,
as compared with nonemergency duties; the risk
was increased by a factor of 2.8 to 14.1 during
alarm response, 2.2 to 10.5 during alarm return,
and 2.9 to 6.6 during physical training
Figure 1A shows the risk of death from
coro-nary heart disease per 1 million firefighters per
year (deaths per 1 million person-years) for each
duty according to age group, and Figure 1B shows
the risk of death according to job status
(volun-teer or professional) As might be expected, the
risk of coronary heart disease generally increased
with age for each type of duty, whereas the results
for job status were mixed
Discussion
In this study, we used data from a nationwide
reg-istry of deaths among firefighters over an 11-year
period and estimates from three different sources
of time spent in various firefighting duties to
estimate the duty-specific risks of death from
coronary heart disease among firefighters As
com-pared with nonemergency duties, certain
emer-gency duties and physical training were
associat-ed with an increasassociat-ed risk of death from coronary
heart disease among firefighters These findings
are consistent with those of our previous, smaller
study18 and with an analysis of cardiac events
that led to retirement from firefighting.22
Fire suppression, which represents only about
1 to 5% of firefighters’ professional time each
year, accounted for 32% of deaths from coronary
heart disease and was associated with a risk of
death from coronary heart disease that was
ap-proximately 10 to 100 times as high as the risk
associated with nonemergency duties We think
that the most likely explanation for these
find-ings is the increased cardiovascular demand of
fire suppression.8,11
The risk of coronary heart disease events
dur-ing fire suppression may be increased because Ta
Trang 6many firefighters lack adequate physical fitness, have underlying cardiovascular risk factors, and have subclinical or clinical coronary heart disease
Even new firefighter recruits may be overweight and have low-to-normal aerobic capacities.23 Such problems are compounded during career tenure because more than 70% of fire departments lack programs to promote fitness and health.1 Most fire departments do not require firefighters to ex-ercise regularly, undergo periodic medical exami-nations, or have mandatory return-to-work eval-uations after a major illness In addition, several studies have shown the high prevalence of risk factors for cardiovascular disease among fire-fighters24-29 as well as lower-than-expected exer-cise tolerance.30,31 Moreover, two studies have shown that among firefighters who had fatal events18 or nonfatal events22 related to coronary heart disease while on duty, 26% and 18%, respec-tively, had previously received a diagnosis of coro-nary heart disease, peripheral vascular disease,
or cerebrovascular disease, and among the der, smoking, hypertension, and diabetes melli-tus were significantly more prevalent than among active firefighters in the control group Likewise,
remain-in our study, the risk of death from coronary heart disease increased with age for all types of duty Unexpectedly, professional and volunteer firefighters had different risks of death from coronary heart disease, depending on the type of duty performed, although for both groups, the risk was highest during fire suppression
In parallel with our finding of a significantly increased risk of death from coronary heart dis-ease during fire suppression, as compared with nonemergency duties, the risk was significantly elevated during physical training This finding is consistent with investigations implicating intense physical activity as a strong triggering factor, es-pecially among physically inactive persons.32-35Also consistent with the triggering hypothesis and with research documenting increased heart rates among firefighters responding to alarms8,9was our finding that the risk of death from coro-nary heart disease associated with alarm response and alarm return was approximately five to seven times as high as that associated with nonemer-gency duties Emergency medical services and other nonfire emergency responses were not as-sociated with a significant increase in risk These findings are consistent with the much lower pro-portion of deaths from coronary heart disease among emergency medical services workers who are not firefighters3 than among firefighters, and may reflect a lower level of exposure to physically demanding emergencies
One limitation of our study is that the mates of odds ratios for specific job duties are based on fairly wide approximations of time spent
esti-on different duties The average work year of a professional firefighter in a major urban center
is probably much different from that of a rural volunteer firefighter In addition, there have been few if any comprehensive studies of how fire-
Training as Compared with Firefighters Engaged in Nonemergency Duties.*
Odds Ratio (95% CI) P Value Odds Ratio(95% CI) P Value Odds Ratio(95% CI) P Value Fire suppression 53 (40–72) <0.001 12.1 (9.0–16.4) <0.001 136 (101–183) <0.001 Alarm response 7.4 (5.1–11) <0.001 2.8 (1.9–4.0) <0.001 14.1 (9.8–20.3) <0.001 Alarm return 5.8 (4.1–8.1) <0.001 2.2 (1.6–3.1) <0.001 10.5 (7.5–14.7) <0.001 Emergency medical services and
other nonfire emergencies 1.3 (0.9–2.0) 0.16 0.5 (0.3–0.8) <0.001 2.6 (1.8–3.9) <0.001Physical training 5.2 (3.6–7.5) <0.001 2.9 (2.0–4.2) <0.001 6.6 (4.6–9.5) <0.001 Nonemergency duties (fire sta
itan fire departments are from surveys of 17 large metropolitan fire departments conducted by the International Associ ation of Fire Fighters (2005) (MooreMerrell L.: personal communication) National data are from annual national sur veys conducted by the National Fire Protection Association (1994 through 2003) 20
Trang 7fighters spend their time Our estimate of the
increase in risk is therefore subject to
considera-ble uncertainty However, even in the most
conser-vative scenario (with the use of the time estimates
from the large metropolitan fire departments), the
risks associated with fire suppression remained
remarkably high and were also significantly
in-creased for alarm response, alarm return, and
physical training
Also, our three sets of risk estimates are not
based on three completely distinct calculations
In each case, one set of national figures for
“ob-served” deaths was used, and the resulting odds
ratios represent risk relative to nonemergency
duties, not absolute risks for one group of
fire-fighters as compared with another Our results
should therefore not be used to suggest that the
risk of death from coronary heart disease during
fire suppression is higher in a small community
fire department than in a large metropolitan fire
department Instead, the three calculations
pro-vide a range of estimates of the average risk for
firefighters nationwide Because only 14% of
fire-fighters in the United States serve populations
larger than 100,000 residents,21 we think that the
average risk for most firefighters probably falls
between the risk based on estimates of time
spent in particular duties that were derived from
a single municipal fire department and the risk
based on the nationwide time estimates Our
es-timate that fire suppression accounts for 1 to 2%
of annual work time (for the nationwide and
mu-nicipal scenarios, respectively) is consistent with
a study of a large fire department in Montreal,36
where fire suppression accounted for 0.7 to 2.5%
of annual work time
A second limitation of our study was the need
to base our evaluation on brief narratives, which
lacked autopsy information for some of the deaths
However, the misclassification of deaths due to
inadequate information would have contributed
to a random error, most likely diluting the results
of our study toward the null hypothesis Although
26 deaths from cardiovascular but not coronary
heart disease were excluded, this small number
was unlikely to bias the overall results in a
spe-cific direction
A third limitation of our analysis was the
starting assumption that the number of deaths
from coronary heart disease that occur during
any given firefighting duty should be directly
pro-portional to the amount of time spent
perform-ing that duty It is well established, for example, that the risk of coronary heart disease events var-ies according to the time of day,37 as well as the season of the year.38 In this study, we could not examine the circadian pattern of deaths How-ever, in our previous, smaller study18 and in an-other, 10-year analysis,2 67 to 77% of deaths from cardiac causes among on-duty firefighters oc-curred between noon and midnight, as did more than 60% of emergency responses This pattern
is in stark contrast to the peak period for vascular events in the general population, which
cardio-is 6 a.m to noon With respect to season, deaths from cardiac causes among firefighters are most frequent in the winter, as they are in the general population When we analyzed duty-specific risks
Emergency Medical Services
Station Duty
2
6 4
14
8
0
Fire Suppression Response Alarm Return Alarm Physical Training Emergency Medical
Services
Station Duty
RETAKE
SIZE
ICM CASE
H/T Combo
Revised
AUTHOR, PLEASE NOTE:
Figure has been redrawn and type has been reset.
Please check carefully.
REG F
Enon
1st 2nd 3rd
among Firefighters, According to Age (Panel A) and Job Status (Panel B).
Trang 8separately for each of the four seasons, however, the resulting point estimates for each duty re-mained similar in magnitude and close to the range of our original confidence intervals Final-
ly, although we cannot completely account for the effects of the time of day and season, the high-est estimates of these effects on event rates are
at least an order of magnitude smaller than the relative risks we observed for specific duties
In conclusion, we analyzed nationwide data
on deaths among firefighters, as well as three separate estimates of time spent in various fire-fighting duties, to determine the duty-specific risks of death from coronary heart disease among firefighters Our analysis showed that specific
duties, especially fire suppression but also alarm response, alarm return, and physical training, are associated with significant increases in risk.Supported in part by grants from the National Institute for Occupational Safety and Health (T42/CCT122961-02, to Dr Kales) and the Massachusetts Public Employees Retirement Administration Commission (to Dr Kales) The funders had no involvement in the study design, data collection and analysis, writing of the paper, or decision to submit the paper for publi- cation.
Dr Kales and Dr Christiani report serving as paid expert nesses, independent medical examiners, or both in workers’ com- pensation and disability cases, including cases involving fire- fighters No other potential conflict of interest relevant to this article was reported.
wit-We thank Ken Pitts, John Gelinas, and Lori Moore-Merrell for providing fire-department incident, response, activity, and sur- vey data.
Maguire BJ, Hunting KL, Smith GS, Levick NR Occupational fatalities in emer- gency medical services: a hidden crisis
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reaction to alarm, an ECG and heart rate study J Occup Med 1981;23:762-6.
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Haas NS, Gochfeld M, Robson MG, Wartenberg D Latent health effects in firefighters Int J Occup Environ Health 2003;9:95-103.
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org/categoryList.asp?categoryID=955&
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Al-Clark S, Rene A, Theurer WM, shall M Association of body mass index and health status in firefighters J Occup Environ Med 2002;44:940-6.
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PS, Black D, Tracy T Risk factors for nary heart disease among firefighters in Cincinnati Am J Ind Med 1996;30:331- 40.
coro-Soteriades ES, Kales SN, Liarokapis D, Christoudias SG, Tucker SA, Christiani DC Lipid profile of firefighters over time: opportunities for prevention J Occup Envi- ron Med 2002;44:840-6.
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Copyright © 2007 Massachusetts Medical Society.
38.
Trang 10for the EVA-3S Investigators*
From Hôpitaux Sainte-Anne (J.-L.M., B.B.,
E.T.) and Europeén Georges Pompidou
(G.C.), Université René Descartes, Paris;
Hôpitaux La Timone (A.B.) and
Sainte-Marguerite (P.P.), Université de la
Médi-terranée, Marseille; Hôpital Jean Minjoz,
Université de Franche-Comté, Besançon
(T.M., J.-F.B.); Hôpital Henri Mondor,
Université Paris-Val-de-Marne, Créteil
(J.-P.B., H.H.); Hôpitaux Rangueil (V.L.,
A.V.) and Purpan (J.-F.A.), Université Paul
Sabatier, Toulouse; Université Claude
Ber-nard, Lyon (M.L.); Hôpital Roger
Salen-gro, Université du Droit et de la Santé,
Lille (D.L., J.-P.P.); Hôpital Charles Nicolle,
Université de Rouen, Rouen (J.W.);
Hôpi-tal de Bellevue, Université Jean Monnet,
Saint-Etienne (P.G.); Hôpital Côte de
Na-cre, Université de Caen, Caen (F.V.);
Hôpi-tal Général, Université de Bourgogne,
Dijon (M.G.); Nouvelles Cliniques
Nan-taises, Nantes (J.-C.P.); Hôpital
Lari-boisière, Université Denis Diderot, Paris
(P.F.); Hôpital La Milétrie, Université de
Poitiers, Poitiers (J.-P.N.); and Hôpital
Saint-Julien Université Henri Poincaré,
Nancy (X.D.) — all in France Address
reprint requests to Dr Mas at the Service
de Neurologie, Hôpital Sainte-Anne, 1 Rue
Cabanis, 75674 Paris CEDEX 14, France,
or at jl.mas@ch-sainte-anne.fr.
* Investigators and committees of the
Endarterectomy versus Angioplasty
in Patients with Symptomatic Severe
Carotid Stenosis (EVA-3S) trial are
listed in the Appendix.
Results
The trial was stopped prematurely after the inclusion of 527 patients for reasons of both safety and futility The 30-day incidence of any stroke or death was 3.9% after endarterectomy (95% confidence interval [CI], 2.0 to 7.2) and 9.6% after stenting (95% CI, 6.4 to 14.0); the relative risk of any stroke or death after stenting as com-pared with endarterectomy was 2.5 (95% CI, 1.2 to 5.1) The 30-day incidence of dis-abling stroke or death was 1.5% after endarterectomy (95% CI, 0.5 to 4.2) and 3.4% after stenting (95% CI, 1.7 to 6.7); the relative risk was 2.2 (95% CI, 0.7 to 7.2) At
6 months, the incidence of any stroke or death was 6.1% after endarterectomy and 11.7% after stenting (P = 0.02) There were more major local complications after stent-ing and more systemic complications (mainly pulmonary) after endarterectomy, but the differences were not significant Cranial-nerve injury was more common after endarterectomy than after stenting
Conclusions
In this study of patients with symptomatic carotid stenosis of 60% or more, the rates
of death and stroke at 1 and 6 months were lower with endarterectomy than with stenting (ClinicalTrials.gov number, NCT00190398.)
Trang 11Findings from two large randomized,
clinical trials1-3 have established
endarterec-tomy as the standard treatment for severe
symptomatic carotid-artery stenosis As compared
with endarterectomy, stenting avoids the need for
general anesthesia and an incision in the neck that
could lead to nerve injury and wound
complica-tions The costs may be less than those of surgery,
mainly because the hospital stay is shorter
How-ever, stenting also carries a risk of stroke and local
complications, and the long-term efficacy of this
technique is not well known A systematic review 4
of five randomized trials comparing stenting with
endarterectomy5-10 concluded that the current
evi-dence does not support a change from the
recom-mendation of carotid endarterectomy as the
stan-dard treatment for carotid stenosis Several more
trials are in progress in Europe11-13 and the United
States.14
We conducted this trial, which started in
No-vember 2000, to evaluate whether stenting is not
inferior to endarterectomy with regard to the
risks of the procedure and its long-term efficacy
in patients with symptomatic carotid stenosis
In September 2005, the safety committee
recom-mended that enrollment in the trial be stopped
We report on the risks of stroke or death within
30 days and 6 months after treatment
MethodsThe Endarterectomy versus Angioplasty in Patients
with Symptomatic Severe Carotid Stenosis (EVA-3S)
trial, a publicly funded, randomized, noninferiority
trial, was conducted in 20 academic and 10
non-academic centers in France The study was
ap-proved by the ethics committee of Hôpital Cochin
in Paris All patients provided written informed
consent
Centers and Investigators
To join the trial, each center was required to
as-semble a team of physicians comprising at least one
neurologist, one vascular surgeon, and one
inter-ventional physician The neurologist was
respon-sible for the initial evaluation and follow-up of the
patients The vascular surgeon had to have
per-formed at least 25 endarterectomies in the year
before enrollment The interventional physician
had to have performed at least 12 carotid-stenting
procedures or at least 35 stenting procedures in
the supraaortic trunks, of which at least 5 were in
the carotid artery Centers fulfilling all ments except those with regard to the interven-tional physician could join the EVA-3S study and randomly assign patients, but all stenting proce-dures had to be performed under the supervision
require-of an experienced tutor (a clinician who qualified
to perform stenting in this study) until the local interventional physician became self-sufficient (ac-cording to the tutor) and performed a sufficient number of procedures according to the predefined criteria
Patients
Patients were eligible if they were 18 years of age
or older, had had a hemispheric or retinal transient ischemic attack or a nondisabling stroke (or reti-nal infarct) within 120 days before enrollment, and had a stenosis of 60 to 99% in the symptomatic carotid artery, as determined by the North Amer-ican Symptomatic Carotid Endarterectomy Trial (NASCET) method.15 The degree of stenosis war-ranting treatment, set at 70% or more at the start of the trial, was subsequently (in October 2003) set at 60% or more because endarterectomy was shown
to benefit patients with symptomatic stenosis of
50 to 69%.3 The presence of an ipsilateral carotid stenosis of 60% or more had to be confirmed by means of catheter angiography or both duplex scanning and magnetic resonance angiography
of the carotid artery
Patients were excluded if one of the following was present: a modified Rankin score16 of 3 or more (disabling stroke) (on a scale of 0 to 5, with higher scores indicating more severe disability);
nonatherosclerotic carotid disease; severe dem lesions (stenosis of proximal common carotid artery or intracranial artery that was more severe than the cervical lesion); previous revasculariza-tion of the symptomatic stenosis; history of bleed-ing disorder; uncontrolled hypertension or diabe-tes; unstable angina; contraindication to heparin, ticlopidine, or clopidogrel; life expectancy of less than 2 years; or percutaneous or surgical interven-tion within 30 days before or after the study pro-cedure The appearance of the stenotic lesion on angiography was not a factor in the selection of patients
tan-Patients who were suitable candidates for both techniques were randomly assigned to undergo endarterectomy or stenting Randomization was carried out centrally by means of a computer-gen-erated sequence, involving randomized blocks of
Trang 12two, four, or six patients that were stratified ing to study center and degree of stenosis (steno-sis of ≥90% or <90%).
accord-Endarterectomy and Stenting
The goal was for endarterectomy and stenting to
be performed within 2 weeks after randomization
Surgeons performed endarterectomy according to customary practice Carotid stenting had to be car-ried out through the femoral route with the use of stents and protection devices approved by the ac-creditation committee Interventional physicians had to have performed at least two stenting pro-cedures with any new device before its use in the trial In January 2003, the safety committee recom-mended the systematic use of stents with cerebral protection devices because of a higher risk of stroke
in patients treated without cerebral protection17; centers began using them on February 1, 2003 The daily use of aspirin (100 to 300 mg) and clopido-grel (75 mg) or ticlopidine (500 mg) for 3 days be-fore and 30 days after stenting was also recom-mended
Follow-up and End Points
The study neurologists performed follow-up uations at 48 hours, 30 days, 6 months after treat-ment, and every 6 months thereafter The primary end point was a composite of any stroke or death occurring within 30 days after treatment Second-ary outcomes were myocardial infarction, transient ischemic attack, cranial-nerve injury, major local complications, and systemic complications with-
eval-in 30 days after treatment; and composites of any stroke or death within 30 days after treatment plus ipsilateral stroke, any stroke, or any stroke or death within 31 days through the end of follow-up Neu-rologists assessed the degree of disability from stroke 30 days and 6 months after the event Func-tional disability from cranial-nerve injury was cat-egorized as absent, mild, moderate, or severe at the 30-day follow-up visit Neurologists also recorded whether treatment-related outcomes were associ-ated with a delay in discharge The occurrence of stroke, death, and other outcomes was assessed by the events committee, which was unaware of the treatment assignments (except for patients who had local complications)
infe-a true infe-absolute difference between groups in the 30-day risk of stroke or death of no more than 2% (noninferiority margin), and a one-sided alpha of 0.05 A similar difference in the 30-day risk of stroke or death between endarter-ectomy and medical treatment was observed in NASCET.22 Our protocol required that an inde-pendent safety committee review safety issues each time 10 new validated primary outcome events occurred, with no predetermined rule for stopping the trial, and reassess the number of patients required to show an effect after 30 pri-mary outcome events had occurred In Septem-ber 2005, the safety committee recommended stopping enrollment for reasons of both safety and futility On the basis of the observed 30-day risk of stroke or death after endarterectomy, we would have needed to enroll more than 4000 patients to test the noninferiority of stenting (assuming that the relative noninferiority limit was unchanged) Given the observed 30-day risks of stenting, the committee considered it to
be extremely unlikely that the trial, should it continue with more patients, would reach its objectives
Analyses of the 30-day outcomes were based on all patients who were randomly assigned to treat-ment and who underwent carotid repair The re-sults are presented as relative risks with 95% con-fidence intervals (CIs), calculated with the use of superiority analysis We also assessed noninferior-ity, as initially planned We assessed homogeneity
of the relative risks of stroke or death among ters using the Breslow–Day test For this purpose, centers were categorized into three groups, ac-cording to the numbers of patients included in the study (<21, 21 to 40, and >40 patients) Analyses of the 6-month outcomes were based on all patients who were randomly assigned to treatment Rates
cen-of stroke and death were estimated with the use
of the Kaplan–Meier method All data were lyzed according to the intention-to-treat principle All P values are two-sided and were not adjusted for multiple testing We used SAS software (version 8.2) for all analyses The authors vouch for the completeness and veracity of the data and data analyses
Trang 13ana-R esults
Patients and Treatments
By September 2005, 527 patients had been
random-ly assigned to treatment, 7 of whom did not
un-dergo carotid repair (Fig 1) The remaining 520
patients were included in the analysis of the 30-day
risk of stroke or death Three strokes that occurred
between randomization and treatment were not
included in the analysis of the 30-day risk of stroke
or death but were included in the 6-month
analy-sis of outcomes The two groups were similar with
respect to baseline characteristics, except for a
greater proportion of patients 75 years of age or
older and more patients with a history of stroke
in the endarterectomy group and a higher
propor-tion of contralateral carotid occlusion in the
stent-ing group (Table 1)
Characteristics of the endarterectomy and
stent-ing procedures are listed in Table 2 Two patients
underwent a repeated procedure within 48 hours
after the initial endarterectomy owing to
residu-al stenosis or dissection In 13 patients, stenting
was converted intraoperatively to endarterectomy
owing to problems with access Two of these
pa-tients had a stroke before endarterectomy
End Points
Although the trial was intended to assess
noninfe-riority, we observed that stenting carried a greater
risk than did endarterectomy When we analyzed
the data as planned, the 95% CI of the difference
in the 30-day incidence of stroke or death between
stenting and endarterectomy (2.1 to 9.3%) did not
include the 2% limit used to define
noninferior-ity The 30-day incidence of any stroke or death was
3.9% (95% CI, 2.0 to 7.2) after endarterectomy and
9.6% (95% CI, 6.4 to 14.0) after stenting, with a
relative risk of 2.5 (95% CI, 1.2 to 5.1) The
abso-lute risk increase was 5.7%, suggesting that one
additional stroke or death resulted when 17
pa-tients underwent stenting rather than
endarter-ectomy The 30-day incidence of disabling stroke
or death was 1.5% (95% CI, 0.5 to 4.2) after
end-arterectomy and 3.4% (95% CI, 1.7 to 6.7) after
stenting, resulting in a relative risk of 2.2 (95%
CI, 0.7 to 7.2) (Table 3) A greater proportion of
strokes occurred on the day of the procedure in
the stenting group than in the endarterectomy
group (17 of 24 vs 3 of 9, P = 0.05)
The relative risk of stroke or death did not
dif-fer significantly among the centers that enrolled
fewer than 21 patients (relative risk, 1.9; 95% CI, 0.6
to 6.2), those that enrolled 21 to 40 patients tive risk, 3.3; 95% CI, 0.7 to 15.2), and those that enrolled more than 40 patients (relative risk, 2.7;
(rela-95% CI, 0.9 to 8.1) (P = 0.83) The 30-day incidence
of stroke or death was similar among patients treated by interventional physicians who were experienced (11 of 105, or 10.5%), tutored during training (7 of 98, or 7.1%), and tutored after train-ing (7 of 57, or 12.3%) (P = 0.54; chi-square sta-tistic, 1.25)
527 Patients underwent randomization
262 Assigned to endarterectomy
3 Did not undergo endarterectomy
1 Declined
1 Had carotid occlusion
1 Had a stroke before treatment
259 Underwent carotid repair and were included in analysis of the primary outcome
2 Had a TIA between zation and endarterectomy
1 Had a stroke before treatment
261 Underwent carotid repair and were included in analysis of the primary outcome
1 Had a nondisabling stroke
1 Had a TIA and 1 had a cardial infarction between randomization and stenting
Carotid repair was successful in the five patients who had a transient is mic attack (TIA), a nondisabling stroke, or myocardial infarction between randomization and carotid repair The three strokes occurred within 2 days after randomization.
Trang 14che-The 30-day incidence of stroke or death was lower among patients who underwent stenting with cerebral protection (18 of 227, or 7.9%) than among those treated with stenting alone (5 of 20,
or 25%; P = 0.03) However, the relative risk of stroke
or death for stenting over endarterectomy did not differ significantly before systematic use of a ce-rebral protection device was recommended (2.0; 95% CI, 0.8 to 5.0) or after (3.4; 95% CI, 1.1 to 10.0; P = 0.50)
Table 1 Baseline Characteristics of the Patients.*
Characteristic
Endarterectomy Group
Vascular risk factors
Prior surgery or angioplasty — no of patients (%)
Trang 15The relative risk of stroke or death adjusted for
age was 2.4 (95% CI, 1.2 to 4.8) and adjusted for
the presence or absence of a history of stroke was
2.6 (95% CI, 1.3 to 5.2) More patients in the
stent-ing group had contralateral carotid occlusion; none
of them had a stroke after stenting The 30-day
incidence of stroke or death after stenting did not
differ significantly between patients who received
dual antiplatelet therapy (19 of 211, or 9.0%) and
those who received single antiplatelet therapy (4 of
36, or 11.1%; P = 0.75)
There were more systemic complications
(main-ly pulmonary) after endarterectomy and more vere local complications after stenting than after endarterectomy, but these differences were not significant Cranial-nerve injury was significantly more common after endarterectomy than after stenting (7.7% vs 1.1%, P<0.001) The median duration of the hospital stay was shorter after stenting (3 days; interquartile range, 2 to 5) than after endarterectomy (4 days; interquartile range,
se-3 to 5; P = 0.01)
Table 1 (Continued.)
Characteristic
Endarterectomy Group
Brain imaging — no of patients (%)
Infarct corresponding to the qualifying event 133 (51.4) 117 (44.8) 0.16
Contralateral carotid occlusion — no of patients (%) 3 (1.2) 13 (5.0) 0.02
Contralateral stenosis of 60–99% — no of patients (%) 44 (17.0) 31 (11.9) 0.11
* Plus–minus values are means ±SD Proportions, means, and medians were compared with the use of Fisher’s exact
test, Student’s t-test, and the Wilcoxon nonparametric test, respectively.
† This condition was diagnosed before the qualifying event.
‡ Tobacco use was defined as the smoking of one cigarette or more per day.
§ The body-mass index is the weight in kilograms divided by the square of the height in meters.
¶ The modified Rankin score ranges from 0 to 5, with higher scores indicating more severe disability.
∥ The degree of stenosis was measured with the use of digital subtraction angiography or magnetic resonance
angiogra-phy, according to the NASCET method.
Trang 16Table 2 Characteristics of Treatment for 257 Patients Who Completed Endarterectomy and 247 Patients Who Completed Stenting.*
Endarterectomy
Anesthesia — no of patients (%)†
Surgical technique — no of patients (%) Endarterectomy
Number of stents — no of patients (%)
Trang 17Type of stent used — no of patients (%)**
Before systematic use of protection devices recommended
After systematic use of protection devices recommended
Device used
During procedure
Postprocedure
* Plus–minus values are means ±SD Percentages may not total 100 because of rounding.
† Data are missing for one patient.
‡ Data are missing for 14 patients
§ Data are missing for two patients
¶ Data are missing for three patients.
∥ Anticoagulant therapy consisted of low-molecular-weight heparins at prophylactic doses for a few days.
** The stent could not be implanted in one patient.
†† Among the 247 patients who completed stenting, 74 underwent stenting before the recommendation was given and
173 underwent stenting afterward.
Trang 18Table 4 lists the incidence of primary outcome events at 6 months The three composite outcomes were significantly more common after stenting than after endarterectomy.
DiscussionThis trial was stopped early for reasons of both safety and futility The 30-day risk of any stroke
or death was significantly higher after stenting (9.6%) than after endarterectomy (3.9%), resulting
in a relative risk of 2.5 (95% CI, 1.2 to 5.1) though early stopping of randomized clinical tri-als carries a risk of the overestimation of treat-ment effects (i.e., analyzing the data at a “random high”),23 the excess of primary outcome events af-ter stenting was considered large enough (one ad-ditional stroke or death among each 17 patients treated by stenting) for the safety committee to rec-ommend stopping the trial In addition, the ob-served rates of the primary outcome made it very unlikely that the trial would show the noninferior-ity of stenting
Al-The 30-day incidence of stroke or death after endarterectomy was lower in our trial than in pre-vious trials of endarterectomy in symptomatic pa-tients.1,2 The lower surgical risk in our study is
unlikely to be explained by the selection of geons with a very high level of expertise Indeed, the surgeons worked in academic and nonaca-demic centers in various areas of France and had only to have performed 25 endarterectomies in the year before enrollment; there was no upper limit for perioperative stroke and death The base-line characteristics of our patients were similar
sur-to those included in other trials of tomy,2,5 which makes it unlikely that our find-ings are explained by the inclusion of patients at low risk for perioperative stroke or death More-over, to prevent the underreporting of minor strokes in patients who underwent surgery un-der general anesthesia and then were returned to surgical wards, all patients were examined 2 days after the procedure Therefore, the most likely explanation for the low rate of complications from endarterectomy in our trial is that the risks
endarterec-of this procedure have decreased since the otal trials1,2 were conducted
piv-The combination of results of previous trials4yielded a 30-day incidence of stroke or death after endovascular repair of the carotid artery of 8.1% (51 of 632 patients; range, 0.0 to 12.1%) There was significant heterogeneity among these trials, which may have resulted from the use of differ-
or Stenting.*
Unadjusted Relative Risk
Trang 19Table 3 (Continued.)
Unadjusted Relative Risk
no of patients (%)
Femoral pseudoaneurysm or
Lower-limb arterial occlusion
* Proportions were compared with the use of Fisher’s exact test Relative risks were calculated with endarterectomy as
the reference group.
† Among patients who underwent endarterectomy, stroke was caused by cerebral infarction in six patients (including
one who had a disabling nonfatal stroke and none who had a fatal stroke) and cerebral hemorrhage in three
(includ-ing two who had a fatal stroke) All but one of the strokes were ipsilateral to the treated artery Of the nine strokes,
three occurred on the day of the procedure Cerebral hemorrhage occurred 1 hour after the procedure in one patient
and the day after in the two other patients At the time of cerebral hemorrhage, the first patient had received
intrave-nous heparin during the procedure (0.5 mg per kilogram of body weight) and the two other patients were receiving
prophylactic doses of low-molecular-weight heparin.
‡ Among patients who underwent stenting, stroke was caused by cerebral infarction in 21 patients (including 5 who
had disabling nonfatal strokes and 1 who had a fatal stroke) and cerebral hemorrhage in 3 (2 who had disabling
nonfatal strokes and none who had a fatal stroke) All but two of the strokes were ipsilateral to the treated artery Of
the 24 strokes, 17 occurred on the day of the procedure Cerebral hemorrhage occurred 24 hours, 7 days, or 10 days
after the procedure At the time of cerebral hemorrhage, the three patients were receiving dual antiplatelet therapy.
§ Stroke was defined as disabling if the modified Rankin score (on a scale of 0 to 5, with higher scores indicating
more severe disability) was 3 or more for at least 30 days after the event, with an increase of 2 points or more over
the prestroke score.
¶ This patient committed suicide 17 days after endarterectomy.
∥ This patient died suddenly 30 days after stenting.
** Myocardial infarction was defined by at least two of the following criteria: typical chest pain lasting 20 minutes or
more; serum levels of creatine kinase, creatine kinase MB, or troponin at least twice the upper limit of the normal
range; and new Q wave on at least two adjacent derivations or predominant R waves in V 1 (R wave ≥1 mm >S wave
in V 1 ).
†† Bradycardia or hypotension was listed if it required treatment or prolonged monitoring.
‡‡ Systemic complications in the endarterectomy group were infection (mainly pulmonary) in five patients, unstable
angina in one, gastrointestinal bleeding in one, and subdural hematoma in one Six of the eight events were
associ-ated with a delay in discharge.
§§ Systemic complications in the stenting group were infection in two patients, pacemaker implantation in one,
throm-bocytopenia in one, and venous thrombosis in one Four of these five events were associated with a delay in
dis-charge.
¶¶ Two patients had two major local complications each.
∥∥ Hematoma was listed if it required surgery or blood transfusion.
*** Infection was listed if it required surgery or parenteral antibiotic therapy.
††† Femoral pseudoaneurysm or arteriovenous fistula was listed if it required surgery.
‡‡‡ Occlusion or thrombosis was listed if it required percutaneous or surgical treatment.
§§§ Nerve injury in the endarterectomy group was hypoglossal-nerve palsy in 10 patients, palsy of the marginal
mandib-ular branch of the facial nerve in 7, recurrent laryngeal-nerve palsy in 2, and glossopharyngeal-nerve palsy in 1 At
the 30-day follow-up visit, two of the cranial-nerve injuries (hypoglossal-nerve palsy in one patient and recurrent
la-ryngeal-nerve palsy in one patient) were categorized as severe, one of them leading to delayed discharge.
¶¶¶ Nerve injury in the stenting group was hypoglossal-nerve palsy in two patients and Horner’s syndrome in one
pa-tient The patient with Horner’s syndrome had carotid dissection during angioplasty The other two patients had
aborted angioplasty with conversion to surgery At the 30-day follow-up visit, no cranial-nerve injury was categorized
as severe.
Trang 20ent endovascular techniques or different criteria for patient selection The 30-day incidence of stroke after stenting in our study (9.2%) was higher than that in the Stenting and Angioplasty with Pro-tection in Patients at High Risk for Endarterec-tomy (SAPPHIRE) trial10 (3.6%), despite the use
of similar endovascular techniques However, most patients (70%) included in the SAPPHIRE trial had asymptomatic stenosis, which carries a lower risk
of stroke during carotid repair than does tomatic stenosis.20,24 Patients in the Carotid and Vertebral Artery Transluminal Angioplasty Study (CAVATAS)5 were similar to those in our trial, but the majority (77%) underwent carotid angioplasty without stenting, and procedures were not per-formed with the use of cerebral protection devices
symp-A potential bias in the comparison of a tively new procedure such as stenting with an es-tablished procedure such as endarterectomy is the effect of the learning curve Our trial involved cen-ters with staff members who had various degrees
rela-of experience in carotid stenting, including centers
in which investigators treated enrolled patients under the supervision of a tutor We tried to limit the effect of the learning curve through the care-ful training and supervision of interventional phy-sicians We did not find any significant differ-ences in outcome related to the number of stenting procedures performed in individual centers or to the experience of the interventional physicians, although these analyses were able to detect only large differences There may also be a learning
curve related to changes in technique Centers in our trial were not required to use a device from
a particular manufacturer for stenting or cerebral protection, but experience with any new device was required before its use in the trial
Cerebral-protection devices have been oped to reduce embolization of plaque fragments during stenting Uncontrolled studies11,20,21 sug-gest that these devices may reduce the risk of procedural stroke However, one could argue that protection devices may cause additional adverse events in some patients and increase costs
devel-In summary, our results indicate that in tients with symptomatic carotid stenosis of 60%
pa-or mpa-ore, treatment with endarterectomy results
in lower rates of stroke or death at 30 days and
6 months than does stenting Long-term
follow-up is ongoing to determine whether the tage of endarterectomy is sustained A larger number of patients are required to provide defi-nite answers about the risk–benefit profile of stenting, as compared with endarterectomy, and
advan-to permit meaningful subgroup analyses.Supported by a grant from the Programme Hospitalier de Recherche Clinique of the French Ministry of Health (AOM 97066), Assistance Publique–Hơpitaux de Paris.
Dr Beyssen reports having received lecture fees from ev3 and Guidant; and Dr Becquemin, lecture fees from Cordis, Guidant, and Cook No other potential conflict of interest relevant to this article was reported.
We are indebted to Véronique Favret, Ouafia Lakat, and tine Mandet for their outstanding efforts in data management;
Chris-to Ludovic Trinquart for statistical help; and Chris-to Joël Ménard and Nicolas Best for their constant support.
Stenting Group
no of patients (%)
Any stroke or death at 30 days† plus ipsilateral stroke
Any stroke or death at 30 days† plus any stroke between
* P values were obtained with the use of the log-rank test.
† Any stroke or death included a stroke in one patient between randomization and planned endarterectomy (which was celed) and strokes in two patients between randomization and planned stenting (which was canceled in one patient).
can-appendix
The following investigators (with the number of patients randomly assigned at each center given in parentheses) and committees
par-ticipated in the EVA-3S trial: Hơpital Purpan, Toulouse (52) — J.-F Albucher, F Chollet, H Rousseau, C Cognard, M Degeilh, A Barret, J.P Bossavy; Hơpital Rangueil, Toulouse (52) — A Viguier, V Larrue, H Rousseau, P Arrué, P Tall, Y Glock; Hơpital Sainte-
Marguerite, Marseille (47) — B Denis, S Cohen, F Nicoli, J.M Bartoli, P Piquet; Hơpital Nord, Hơpital de Bellevue, Saint-Etienne (43)
Trang 21— P Garnier, C Veyret, F.G Barral, J.P Favre, X Barral; Hơpital Cơte de Nacre, Caen (40) — F Viader, A Duretête, L Carluer, J
Théron, P Courthéoux, O Coffin, D Mạza; Hơpital Sainte-Anne, Hơpital Cochin, Hơpital Georges Pompidou, Paris (29) — E Touzé,
C Arquizan, C Lamy, D Calvet, V Domigo, B Beyssen, J.F Méder, D Trystram, P.O Sarfati, P Julia, J.N Fabiani; Hơpital Général,
Hơpital du Bocage, Dijon (28) — M Giroud, G.V Osseby, O Rouaud, I Benatru, D Krause, J.P Cercueil, R Brenot, M David; Hơpital
Henri Mondor, Créteil (26) — H Hosseini, H Kobeiter, J.-P Becquemin, P Desgranges; Nouvelles Cliniques Nantaises, Nantes (21)
— G Hinzelin, A Bouyssou, J.-C Pillet; Hơpital Lariboisière, Paris (20) — P Favrole, K Berthet, C Gobron, M.G Bousser, R Chapot,
E Houdart, C Petitjean; Hơpital Roger Salengro, Lille (20) — C Lucas, H Hénon, C Lefebvre, D Leys, M.A Mackowiak-Cordoliani, X
Leclerc, J.-P Pruvo, M Koussa; Hơpital La Milétrie, Poitiers (17) — J.P Neau, G Godenèche, H Moumy, J Drouineau, J.B Ricco;
Hơpital Central, Nancy, Hơpital Brabois, Vandoeuvre les Nancy (15) — X Ducrocq, J.C Lacour, S Bracard, C Amicabile, O Hassani, G
Fiévé; Hơpital Charles Nicolle, Rouen (12) — Y Onnient, B Mihout, E Clavier, J Thiebot, J Watelet, D Plissonnier; Clinique Pasteur,
Toulouse (11) — J.R Rouane, J.C Laborde, B Escude, F Berthoumieu; Fondation Hơpital Saint-Joseph, Marseille (12) — R Padovani,
O Bayle, P Bergeron, J.M Jausseran; Hơpital La Timone, Marseille (10) — L Milandre, J.M Bartoli, G Moulin, A Branchereau, P.E
Magnan; Hơpital Pellegrin Tripode, Bordeaux (10) — F Rouanet, J Berge, X Barreau, D Midy, J.C Baste; Hơpital Privé Beauregard,
Marseille (10) — H Guinot, P Commeau, F Houel; Hơpital Civil, Strasbourg (10) — V Wolff, J.M Warter, R Beaujeux, C Jahn, J.G
Kretz; Hơpital Bretonneau, Tours (9) — D Saudeau, I Bonnaud, D Herbreteau, P Lermusiaux, R Martinez; Polyclinique,
Essey-les-Nancy (8) — I Masson, M Amor, J.P Carpena, C Amicabile; Hơpital Saint-Roch et Hơpital Pasteur, Nice (6) — M.H Mahagne, J
Baque, J Sedat, M Dib, R Hassen-Khodja, M Batt; Hơpital Saint-Jean, Perpignan (5) — D Sablot, J.L Bertrand, M Beaufigeau, G.A
Pelouze; Hơpital Bichat-Claude Bernard, Paris (4) — P Amarenco, O Simon, E Meseguer, P Lavallée, H Abboud, E Houdart, M
Mazighi, G Lesèche; Polyclinique du Bois, Lille (3) — M Combelles, V Courteville, G Gozet, C Depriester, I Lambert, J Pommier;
Hơpital E Muller, Mulhouse (3) — G Rodier, D Weisse, J Aventin, G Dalcher; Clinique du Belvédère, Nice (2) — P Marcel, P Maillet,
J.M Gagliardi; Hơpital Jean Minjoz, Besançon (1) — T Moulin, J.-F Bonneville, J.Y Huart; Fondation Saint-Joseph, Paris (1) — C
Gauthier, J.M Pernes, C Laurian; Scientific Committee — J.-L Mas (chair), G Chatellier (cochair), J.-P Becquemin, J.-F Bonneville,
A Branchereau, D Crochet, J.C Gaux, V Larrue, D Leys, J Watelet; Events Committee — T Moulin (chair), S Bracard, M Hommel,
J.L Magne, F Mounier-Vehier, S Weber; Accreditation Committee — B Beyssen (chair), J.-F Bonneville, L Boyer, J.P Favre, M
Gir-oud, K Hassen-Kodja, J.B Ricco; Imaging Committee — J.-P Pruvo (chair), J.F Meder (cochair), C Arquizan, F Becker, F Cattin, J.M
Debray, J.M Jausseran, A Long, O Naggara, P.J Touboul; Safety Committee — M Lièvre (chair), J.P Beregi, J Bogousslavsky, M Testart.
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