# Cost-effectiveness of screening of coronary artery disease in patients with type 2 DIABetes at a very high cardiovascular risk (SCADIAB study) rational and design

Kamel Mohammedi, Nathalie Preaubert, Tanguy Cariou, Vincent Rigalleau, Ninon Foussard, Laurent Piazza, Celine Bairras-Martin, Thierry Couffinhal, Julien Bezin, Antoine Benard

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## To cite this version:

Kamel Mohammedi, Nathalie Preaubert, Tanguy Cariou, Vincent Rigalleau, Ninon Foussard, et al. Cost-effectiveness of screening of coronary artery disease in patients with type 2 DIABetes at a very high cardiovascular risk (SCADIAB study) rational and design. Cardiovascular Diabetology, 2021, 20 (1), pp.63. 10.1186/s12933-021-01253-2. hal-03223164

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# Cost-effectiveness of screening of coronary artery disease in patients with type 2 DIABetes at a very high cardiovascular risk (SCADIAB study) rational and design

Kamel Mohammedmedi¹,²,³*, Nathalie Préaubert⁴, Tanguy Cariou⁵, Vincent Rigalleau¹,², Ninon Foussard¹, Laurent Piazza⁴, Céline Bairras-Martin⁶, Thierry Couffinhal²,³,⁷, Julien Bezin²,⁸,⁹ and Antoine Benard⁵,¹⁰

**Abstract**

**Background:** Screening for coronary artery disease (CAD) remains broadly performed in patients with type 2 diabetes (T2DM), although the lack of evidence. We conduct a real-world evidence (RWE) study to assess the risk of major clinical outcomes and economic impact of routine CAD screening in T2DM individuals at a very high cardiovascular risk.

**Methods:** SCADIAB is a comparative nationwide cohort study using data from the French National Health Data System. The main inclusion criteria are: age ≥ 40 years, DT2 diagnosed for ≥ 7 years, with ≥ 2 additional cardiovascular risk factors plus a history of microvascular or macrovascular disease, except CAD. We estimated ≥ 90,000 eligible participants for our study. Data will be extracted from 01/01/2008 to 31/12/2019. Eligible participants will be identified during a first 7-year selection period (2008–2015). Each participant will be assigned either in experimental (CAD screening procedure during the selection period) or control group (no CAD screening) on 01/01/2015, and followed for 5 years. The primary endpoint is the incremental cost per life year saved over 5 years in CAD screening group versus no CAD screening. The main secondary endpoints are: total 5-year direct costs of each strategy; incidence of major cardiovascular (acute coronary syndrome, hospitalization for heart failure, coronary revascularization or all-cause death), cerebrovascular (hospitalization for transient ischemic attack, stroke, or carotid revascularization) and lower-limb events (peripheral artery disease, ischemic diabetic foot, lower-limb revascularization or amputation); and the budget impact for the French Insurance system to promote the cost-effective strategy. Analyses will be adjusted for a high-dimension propensity score taking into account known and unknown confounders. SCADIAB has been funded by the French Ministry of Health and the protocol has been approved by the French ethic authorities. Data management and analyses will start in the second half of 2021.

**Discussion:** SCADIAB is a large and contemporary RWE study that will assess the economic and clinical impacts of routine CAD screening in T2DM people at a very high cardiovascular risk. It will also evaluate the clinical practice regarding CAD screening and help to make future recommendations and optimize the use of health care resources.

<footnote>*Correspondence: km.mmohammedmedi@gmail.com
¹Department of Endocrinology, Diabetes and Nutrition, Bordeaux University Hospital, Hôpital Haut-Lévêque, Avenue de Magellan, 33604 Pessac Cedex, France
Full list of author information is available at the end of the article</footnote>
Trial registration ClinicalTrials.gov Identifier: NCT04534530 (https://clinicaltrials.gov/ct2/show/NCT04534530)

**Keywords:** Type 2 diabetes, Coronary artery disease, Cardiovascular risk, Major adverse cardiac events, Screening, Real-world evidence study, Cost-effectiveness, Economic impact

**Background**

Type 2 Diabetes mellitus (T2DM) is a major public health problem, responsible for a wide range of clinical, economic and societal issues [1–4]. Despite the substantial improvement in cardiovascular prognosis observed in recent decades, cardiovascular disease, essentially coronary artery disease (CAD), remains the leading cause of death [5]. CAD is often severe and silent in patients with T2DM [6–10], which may encourage a systematic

and broad screening in asymptomatic individuals. Previous randomized controlled trial (RCT) did not provide evidence that routine screening for silent CAD may reduce the incidence of major cardiovascular events and death in people with T2DM [11–15]. Only one previous study showed that screening for silent CAD, compared with no screening, was associated with a reduced risk of minor cardiovascular events in T2DM patients with at least 2 cardiovascular risk factors [16]. However, the

<table><caption>**Table 1 Randomized controlled trials evaluating the effect of systematic screening of coronary artery disease in the risk of major cardiovascular adverse events in people with diabetes**</caption><thead><tr><th>Study</th><th>Population</th><th>Inclusion period</th><th>Follow-up (years)</th><th>Primary outcome</th><th>Sample size</th><th>Number of events</th><th>Expected incidence (%/year)</th><th>Observed incidence (%/year)</th><th>Hazard ratio (95% CI)</th></tr></thead><tbody><tr><td>Faglia et al. [16]</td><td>T2DM Age 46–75 years +≥ 2 CV risk factors</td><td>1998–1999</td><td>4.5</td><td>Major (cardiac death or MI) or minor (resting and effort angina) event</td><td>141</td><td>19</td><td>3</td><td>3</td><td>-</td></tr><tr><td>DIAD [11]</td><td>T2DM Age 50–70 years</td><td>2000–2002</td><td>4.8</td><td>Non-fatal MI or CV death</td><td>1123</td><td>32</td><td>1–2</td><td>0.6</td><td>0.88 (0.44–1.88)</td></tr><tr><td>DYNAMIT [12]</td><td>DT2M Age 55–75 years +≥ 2 CV risk factors</td><td>2000–2003</td><td>3.5</td><td>All-cause death, non-fatal MI, non-fatal stroke, HH requiring hospitalization or visit to emergency department</td><td>631</td><td>54</td><td>5.5</td><td>2.4</td><td>1.00 (0.59–1.71)</td></tr><tr><td>FACTOR-64 [13]</td><td>T2DM + T1DM Men ≥ 50, Women ≥ 55 years diabetes duration ≥ 3 years or Men ≥ 40 years, Women ≥ 45y + Diabetes duration ≥ 5 years</td><td>2007–2013</td><td>4.0</td><td>All-cause death, nonfatal MI, or hospitalization for unstable angina</td><td>900</td><td>62</td><td>8</td><td>1.7</td><td>0.80 (0.49–1.32)</td></tr><tr><td>DADDY-D [14]</td><td>T2DM Age 50–70 years 10-year CV risk score ≥ 10%</td><td>2007–2012</td><td>3.6</td><td>Non-fatal MI or CV death</td><td>520</td><td>26</td><td>2.6</td><td>1.4</td><td>0.85 (0.39–1.83)</td></tr></tbody></table>

T2DM type 2 diabetes mellitus, T1DM type 1 diabetes mellitus, CV cardiovascular, MI myocardial infarction, HH heart failure
results of this monocentric and small sized study have never been corroborated by subsequent RCTs, although larger, multicentric and testing hard and validated clinical outcomes (major cardiovascular events and all-cause death) (Table 1). The DIAD (Detection of Ischemia in Asymptomatic Diabetics) study showed a comparable 4.8-year incidence of major cardiovascular event (a composite of cardiovascular death or non-fatal myocardial infarction) in 1123 T2DM participants who experienced CAD screening compared with those who did not [11]. Similar findings were reported in further large multicenter RCTs and a meta-analysis [12–15]. Nevertheless, some uncertainties remain in terms of benefit of CAD screening strategy in T2DM patients at very high cardiovascular risk, particularly those with peripheral atherosclerosis, chronic kidney disease (CKD) or any microvascular disease.

Despite this lack of evidence, most of guidelines recommend systematic screening for silent CAD in asymptomatic individuals with diabetes and high or very high cardiovascular risk [17–20]. Hence, a majority of physicians practice routine screening for silent CAD in patients with diabetes. We conducted a preliminary survey (unpublished data) in France in 2019 to determine the practices of 605 physicians in terms of screening for silent CAD in T2DM patients at a very high cardiovascular risk. A majority of participants (80% of cardiologists and 69% of diabetologists) reported a routine CAD screening practice with a sustained frequency: once a year (42%), once/2 years (20%), and once/3 years (33%).

A routine CAD screening induces high healthcare expenses as it leads to invasive investigations, endovascular and surgical revascularizations as well as intensification of pharmacological therapies. To the best of our knowledge, the cost-effectiveness of routine CAD screening has not been evaluated prospectively in population with T2DM and a very high cardiovascular risk. Only two economic studies, based on Markov models, have addressed this question by comparing different strategies in Japanese and American populations: no screening, screening (with stress echocardiography, myocardial scintigraphy coupled with stress test, or stress electrocardiogram) [21, 22]. Their results were very limited by model's hypothesis; uncertainty surrounding epidemiological and utilities data used; and costs of care, which may differ greatly across countries. In this context of discrepancy between lack of evidence and current guidelines and clinical practice, we aim to estimate the effectiveness and cost-effectiveness of systematic CAD screening in patients with T2DM and a very high cardiovascular risk.

# Methods

## Study overview and design

The Cost-effectiveness of Screening of Coronary Artery disease in patients with type 2 DIABetes at a very high cardiovascular risk (SCADIAB) study is a retrospective and comparative real-world evidence (RWE) cohort study using data from the French National Health Data System (SNDS, *Système National des Données de Santé*), a claim database encompassing 98,8% of the whole French population [23].

## Study population

### Inclusion criteria

Eligible participants must meet all of the following criteria:

Age = 40 years or older,
Affiliation to the general health insurance scheme in France,
Diagnosis of T2DM,
Duration of T2DM ≥ 7 years,
Two or more additional cardiovascular risk factors (obesity, hypertension, hypercholesterolemia, or tobacco smoking using the chronic obstructive pulmonary disease (COPD) as a proxy),
At least one microvascular or macrovascular disease: carotid stenosis, transient ischemic attack (TIA), stroke, lower-limb peripheral artery disease (PAD), CKD, severe diabetic retinopathy with requirement of laser photocoagulation, or peripheral or autonomic diabetic neuropathy.

Diagnosis will be determined based on the list of 100% health insurance coverage for chronic diseases in France (including T2DM, hypertension, TIA, stroke, PAD, CKD, COPD), the history of diseases of interest or surgery (coronary, carotid or lower-limb revascularization, bariatric surgery, kidney transplantation) according to the International Classification of Diseases Code Tenth Revision (ICD-10) (Additional file 1: Table S1), or at least 3 deliveries of one or more corresponding drugs as appropriate (antidiabetic, anti-obesity, antihypertensive or lipid-lowering drugs) over one year.

### Exclusion criteria

One of the following:

The presence of CAD (defined as a history of acute coronary syndrome, coronary revascularization, angina pectoris, or unstable angina).
Any visit to an emergency department for chest pain resulting for admission to a cardiac intensive care unit.

## Recruitment of participants and follow-up

The data will be extracted from January 1, 2008 to December 31, 2019. A selection period will be defined by the 7 years (January 1, 2008 to December 31, 2014) preceding the index date. It will enable us to identify eligible patients and measure all the variables needed for the calculation of the high dimension propensity score (hdPS). Each participant will be assigned to one of the two study groups on the index date (January 1, 2015), and then followed up to December 31, 2019 (Fig. 1).

## Study groups and methods of CAD screening

### Screening group

Individuals who had at least one screening exam (stress electrocardiogram test, stress echocardiography,

myocardial scintigraphy coupled with stress test or pharmacological stimulation using adenosine, or coronary CT scan) (Table 2) during the selection period (2008–2015).

### No-screening group

Participants who never experienced a screening exam as described above during the selection period (2008–2015), except resting electrocardiogram.

## Study endpoints

### Primary endpoint

The incremental cost per life year saved over 5 years in CAD screening group versus no CAD screening.

## Secondary endpoints

### Economic endpoints

(1) A cost-consequence analysis linking the total 5-year direct costs of each strategy (drugs, medical visits, hospitalizations, nursing visits, biological and radiological

<figure><img src="image_4.png" /><figcaption>**Table 2** Codes used to identify tests to screen coronary artery disease</figcaption></figure>

<table><thead><tr><td>Tests</td><td>Procedure codes</td></tr></thead><tbody><tr><td>Stress test</td><td>DKRP004, EQRP002, EQRM001</td></tr><tr><td>Myocardial scintigraphy coupled with stress test or pharmacological stimulation using adenosine</td><td>DAQL001, DAQL010, DAQL011, DAQL009</td></tr><tr><td>Stress echocardiography</td><td>DAQM003, DZQM002, DBQM001</td></tr><tr><td>Coronary CT scan</td><td>ECQH010</td></tr><tr><td colspan="2">Procedure codes: Codes of the French classification of medical procedure (CCAM)</td></tr></tbody></table>
exams, technical exams, medical transports...) and the
total number of major cardiovascular and renal events
over 5 years; (2) the budget impact (in €) for the French
Insurance system to promote the most cost-effective
strategy between routine CAD screening and no screen-
ing; and (3) the total care consumption over the follow-
up period.

Clinical endpoints

The effects of CAD screening (versus no CAD screen-
ing) in terms of major adverse cardiac events (the first
occurrence of any component of the composite out-
come, which comprise acute coronary syndrome, coro-
nary revascularization, hospitalization for heart failure
or all-cause death); major cerebrovascular events (the
first occurrence either of stroke, hospitalization for TIA,
or carotid revascularization); major adverse limb events
(the first occurrence of any component of the composite
outcome, comprising PAD, ischemic diabetic foot, lower-
limb revascularization (angioplasty or surgery) or ampu-
tation); and CKD or end-stage kidney disease (ESKD,
defined as requirement of any sustained renal replace-
ment therapy or kidney transplantation). Each compo-
nent of these composite endpoints will also be considered
individually. Major cerebrovascular events, major adverse
limb events and ESKD will be considered during follow-
up among participants without a history of each appro-
priate condition at baseline. Clinical endpoints will be
determined according to ICD-10 and codes of the French
classification of medical procedure (CCAM) as presented
in Additional file 2: Table S2.

Finally, SCADIAB study will also assess the frequency
of routine CAD screening, expressed as the number of
examinations performed per individual per year.

Statistical considerations

Sample size estimation

Among 3.3 million people treated for diabetes mellitus
in France, at least 3 million are estimated to have T2DM.
Based on previous data, about 2.4 million T2DM indi-
viduals would be free of a history of CAD, 38% would
have at least two cardiovascular risk factors, and a his-
tory of microvascular or macrovascular disease would be
present in more than 10% of patients [24, 25]. Hence, we
estimated that at least 90,000 patients would be eligible
for our study.

Statistical analysis plan

The data will be analysed by the biostatistician of the
“Clinical Epidemiology Unit” of the University Hospital
of Bordeaux (USMR). Analyses will be performed using
SAS® software, version 9.4 or later (SAS Institute, Cary,

NC, USA, http://www.sas.com) and all tests will be per-
formed at the first-order error risk α = 5%. The flow-chart
(CONSORT), as well as the characteristics of patients
at inclusion (eligibility criteria, epidemiological, clinical,
biological characteristics and treatment use) will be pre-
sented. Confounding factors will be taken into account
through a hdPS score that will involve around 500 vari-
ables, according to the Bross formula [26]. A princi-
pal component analysis will then allow us to reduce the
dimensionality to 30 components, and the goodness
of fit of this hdPS score will be estimated by a graphical
comparison of the score distribution and by standard-
ized mean differences between the two study groups [27].
Comparisons between the two groups will be carried out
with and without adjustment for the hdPS score, and the
hypotheses of the different regression models chosen,
will be systematically verified.

Regarding the analysis of the primary endpoint, a gross
estimate of the incremental cost per life-year gained at
5 years will be conducted. The confidence interval (CI)
of this incremental cost-effectiveness ratio will be esti-
mated by bootstrap (5000 iterations). The analysis will be
performed as Intent to Treat. To investigate a possible
relationship between the frequency of screening and sur-
vival, we will define four different subgroups: screening
conducted at least once a year, less than once a year (and
at least once every two years), less than once every two
years (and at least once every three years), and only once
during the follow-up period.

A cost-consequence analysis will be performed linking
results of all direct costs (observed during the following
period) and results on major cardiovascular events. A
budget impact analysis will be conducted to determine
the public expenses of the spread of a systematic screen-
ing for silent ischemic CAD.

Cardiovascular events will be expressed as numbers,
cumulative incidence and incidence rates. Kaplan-Meier
curves will be elaborated to plot the incidence of end-
points according to study groups (CAD screening versus
no screening). Unadjusted comparisons between groups
will be done using a log-rank test. Cox proportional haz-
ards regression models will be computed to estimate
Hazard ratios, with related 95% CIs, after adjustment for
hdPS score.

Study progress

The study protocol has been approved by the French
ethic authorities (see “Declarations” section below). Pro-
cedures and contracts for access to the SNDS databases
are in progress. Data management and analyses will start
in the second half of 2021, and the main results will be
published in 2022.
Discussion

We will conduct a large RWE study to investigate the risk of major clinical outcomes and economic impact of routine CAD screening in individuals with T2DM and a very high risk for cardiovascular disease in France. We will perform a retrospective analysis using the electronic health record (EHR) data from the SNDS databases which represent almost the entire French population allowing us sufficient sample size to address the investigated question.

Screening for silent CAD and risk of major cardiovascular events

Previous RCTs demonstrated no clinical benefit asso-
ciated with routine CAD screening in asymptomatic
T2DM patients, but population with a high cardiovascu-
lar burden and any organ vascular damage has not been
investigated [11–14]. Also, the observed incidence of out-
comes was much lower than expected in published RCTs
evaluating the interest of routine CAD screening in indi-
viduals with T2DM (Table 1). The conduction of a new
prospective RCT will be too expensive, time-consuming
with difficulties for recruiting asymptomatic participants
with a very high cardiovascular risk. Indeed, the DYNA-
MIT (Do You Need to Assess Myocardial Ischemia in
Type-2 diabetes) study was stopped prematurely due to
difficulties in recruitment of participants and a low inci-
dence of cardiovascular events [12]. DYNAMIT included
only one-fifth (631/3000) of the originally planned enrol-
ment to detect a 20% relative risk reduction (RRR) in the
primary endpoint (a composite of all-cause death, non-
fatal myocardial infarction, non-fatal stroke, or heart
failure requiring hospitalization or visit to emergency
department) in people with T2DM at a high cardiovascu-
lar risk (aged 55 to 75 years with at least 2 other cardio-
vascular risk factors). A recent meta-analysis estimated
that a large number of participants would be needed to
demonstrate a potential benefit of the systematic CAD
screening strategy to reduce the incidence of major car-
diovascular events [15]. The optimal sample size for 20%
RRR of major cardiac events should be 29,763 partici-
pants (19,548 for all-cause death). Therefore, a retrospec-
tive RWE study seems to be an appropriate approach to
evaluate the long-term cost-effectiveness of systematic
CAD screening strategy in T2DM subjects at a very high
cardiovascular risk without known history of CAD. Of
note, among 3.7 million people with diabetes in France,
we estimate that at least 90,000 individuals will be eligible
for our study in the SNDS database.

Cost-effectiveness of routine CAD screening in patients
with diabetes

Systematic CAD screening strategy leads to more inva-
sive examination, especially coronary angiography, which
is associated with increased risk of complications [11,
12]. Routine CAD screening encourages also revascu-
larizations and intensification of pharmacological treat-
ments, despite uncertainties in terms of related benefits.
In the FACTOR-64 study, CAD screening was not asso-
ciated with a significant reduction in major cardiovas-
cular events despite intensive pharmacological control
of cardiovascular risk factors (and some coronary revas-
cularizations) in patients with a positive screening test,
while individuals assigned to control group and those
with a negative screening test had only conventional
cardiovascular treatment goals [13]. Furthermore, BAR-
DOT (Basel Asymptomatic high-Risk Diabetics' Out-
come Trial) study showed that combined medical therapy
and invasive strategy (coronary angiography followed or
not by revascularization) for silent CAD, compared with
medical treatment alone, was associated with reduced
scintigraphic CAD progression, but no significant dif-
ference was observed in terms of hard clinical events in
high risk T2DM patients [28]. Therefore, to avoid unjus-
tified health expenses and misuse of collective resources
associated with routine CAD screening, we conduct the
SCADIAB study to assess the cost-effectiveness of this
strategy in people with T2DM and a very high cardiovas-
cular risk.

Strengths and limitations

The key strength of our study is the collection of a com-
prehensive range of clinical features, cardiovascular pro-
cedures, history of pharmacological therapies or surgery,
major events and survival status in the whole French pop-
ulation of patients with T2DM and a very high cardiovas-
cular risk during an overall period of 12 years. SCADIAB
findings will have a broader generalizability for all T2DM
patients at a very high cardiovascular risk. Our study
will provide a line of complementary evidence (further
to RCTs' findings) in terms of routine CAD screening in
a contemporary cohort of patients with T2DM in real-
world settings. SCADIAB will be more economical and
time efficient than RCT, but a number of intrinsic limi-
tations need to be acknowledged. The retrospective and
non-randomized design of our study is subject to bias
选修
(selection, information, detection) and confounding fac-
tors. To limit selection bias, our study population will be
rigorously defined using pre-specified inclusion criteria
(T2DM for at least 7 years, with at least 2 cardiovascu-
lar risk factors and one or more organ damage) extracted
from reliable and valid SNDS database. The 7-year selec-
tion period leading to assignment of each individual to
one of the two study arms (CAD screening or absence
of CAD screening) will limit information bias. We will
use validated algorithms to identify inclusion criteria
and endpoints [29–31]. Also, the cardiovascular inves-
tigation required for study arms assignment (stress test,
scintigraphy, stress echocardiography...) will be recorded
exhaustively in the SNDS database. We believe that the
detection bias will be limited in our study as we have
access to the SNDS database covering the whole French
population including death registry. Finally, we will use
the hdPS method to control measurable confounding fac-
tors as well as unknown or unmeasurable ones [32–34].

Conclusions

SCADIAB study is the first investigation of the cost-effec-
tiveness of CAD screening strategy in T2DM patients
with a very high cardiovascular risk. It will evaluate the
economic impact and clinical benefits of routine CAD
screening in this population. It will also evaluate the clin-
ical practice regarding CAD screening. SCADIAB will
provide essential information for payers, clinicians, and
scientific societies in terms of long-term efficiency of sys-
tematic CAD screening in a large T2DM population. Our
study will also measure the economic performance of
CAD screening in a real-world setting, with an accurate
comparison with no CAD screening strategy. The SCA-
DIAB findings will help to optimize the use of health care
resources and guide clinical decision-making and future
recommendations.

Abbreviations

BARDOT: Basel Asymptomatic high-Risk Diabetics' Outcome Trial; CAD:
Coronary Artery Disease; CCAM: Classification Commune des Actes Médicaux
(The French classification of medical procedures); CI: Confidence Interval;
CKD: Chronic Kidney Disease; COPD: Chronic Obstructive Pulmonary Disease;
DYNAMIT: Do You Need to Assess Myocardial Ischemia in Type-2 diabetes;
EHR: Electronic Health Record; ESKD: End-Stage Kidney Disease; HDPS: High-
Dimension Propensity Score; ICD-10: International Classification of Diseases
Code Tenth Revision; PAD: Peripheral Artery Disease; RCT: Randomized Con-
trolled Trial; RRR: Relative Risk Reduction; RWE: Real-World Evidence; SCADIAB:
Cost-effectiveness of Screening of Coronary Artery disease in patients with
type 2 DIABetes at a very high cardiovascular risk; SNDS: Système National des
Données de Santé (The French National Health Data System); T2DM: Type 2
Diabetes Mellitus; TIA: Transient Ischemic Attack.

**Supplementary Information**

The online version contains supplementary material available at https://doi.
org/10.1186/s12933-021-01253-2.

Additional file 1: Table S1. Codes used to identify inclusion and exclusion criteria.

Additional file 2: Table S2. Codes used to identify study endpoints.

Acknowledgements

The authors acknowledge the whole teams of the Clinical Research Depart-
ment and the Clinical Epidemiology Unit in Bordeaux university hospital.

Authors' contributions

KM, NP, LP, Th.C, JB and AB designed the study. KM drafted the manuscript with the assistance of NP, Ta.C, JB and AB. VR, NF, CBM and Th.C contributed to discussion and reviewed/edited the manuscript. All authors approved the current version of the manuscript. KM, NP and AB are the guarantors of this work. All authors read and approved the final am manuscript.

Funding

SCADIAB study has been funded by the French Ministry of Health (PRME 2019-0006) (https://solidarites-sante.gouv.fr/systeme-de-sante-et-medico-social/recherche-et-innovation/l-innovation-et-la-recherche-clinique/appels-a-projets/article/les-projets-retenus).

Availability of data and materials

Not applicable.

Declarations

Ethics approval and consent to participate

The study protocol has been approved by the Scientific and Ethical Commit-
tee for Research, Studies and Evaluations in Health (CESREES, reference num-
ber 1609284; September, 3 2020) and the French Data Protection Authority
(CNIL, DR-2020-379; December, 14 2020). Patient consents are not required for
this retrospective analyse of medico-administrative database.

Consent for publication

Not applicable.

Competing interests

Authors declare no other potential conflict of interest relevant to this article.

Author details

¹ Department of Endocrinology, Diabetes and Nutrition, Bordeaux University Hospital, Hôpital Haut-Lévêque, Avenue de Magellan, 33604 Pessac Cedex, France. ² Faculty of Medicine, University of Bordeaux, Bordeaux, France.

³ INSERM Unit 1034, Biology of Cardiovascular Diseases, Pessac, France.

⁴ Health Economics Unit, Clinical Research Department, Bordeaux University Hospital, Talence, France. ⁵ Clinical Epidemiology Unit (USMR), CIC-EC 14-01, Bordeaux University Hospital, Bordeaux, France. ⁶ Internal Promotion Department, Bordeaux University Hospital, DCRI, Talence, France. ⁷ Department of Cardiology, Bordeaux University Hospital, Hôpital Haut-Lévêque, Bordeaux, Pessac, France. ⁸ INSERM, Bordeaux Population Health Research Center, U1219, Team Pharmacoepidemiology, Bordeaux, France. ⁹ Department of Pharmacology, Bordeaux University Hospital, Bordeaux, France. ¹⁰ INSERM, Bordeaux Population Health Research Center, U1219, Team EMOS0, Bordeaux, France.

Received: 19 February 2021 Accepted: 26 February 2021

Published online: 13 March 2021

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