21ème congrès sadiab 2019 - sadiab-dz.comperipheral artery disease 430 (4.8) 0 0 0 430 (8.9) 0...

21ème congrès SADIAB 2019

the International Cholesterol management Practice Study

ICLPS ALGERIA

Pr Abdelkrim Berrah

Service de Médecine interne

Hôpital Dr Mohamed Lamine Debaghine

CHU Bab El Oued Alger

1974,1976

NOBEL 1985

Les preuves

Boekholdt et al JACC 2014

Les preuves

CTT Lancet vol 385 April 11, 2015

Les preuves

Collins R, et al .2016;388:2532-2461

Multiplication des recommandations

Evolution des objectifs

Mach F, et al Eur Heart J 2019;0: 1-78

AACE 2017

ESC/EAS Guidelines 2019

Prévention secondaire Très haut risque Classe I niveau A

Prévention primaire Très haut risque sans HCF Classe I niveau C

Prévention primaire Très haut risque avec HCF Classe IIa niveau C

Mach F et al. Eur Heart J. 2019; 00:1-78

ESC/EAS Guidelines 2019

Prévention secondaire Très haut risque Classe I niveau A

Prévention primaire Très haut risque sans HCF Classe I niveau C

Prévention primaire Très haut risque avec HCF Classe II niveau C

Objectifs Réduction du LDLC d’au moins 50% par rapport au taux de départ et LDLC < 1.4 mmol/l (< 55 mg/l)


ESC/EAS 2019 Evolution des objectifs


Intérêt d’un LDL-C inférieur à 0.55 g/l : Les évidences

Etude L-TAP : Le Gap

Pearson TA et al. Arch Intern Med 2000;160:459-467.

0

20

40

60

80

100

18

95

Médecins Awareness Guidelines

Patients Coronariens à

l’objectif

ICLPS

Palestine

Inclusion:Patients ≥ 18 ans sous statine depuis au moins 3 mois

Objectifs Principal

Evaluer le pourcentage de patients atteignant Les cibles LDL-C selon les recommandations ESC / EAS 2011 pour le management des dyslipidémies compte tenu de leur niveau de risque cardiovasculaire très élevé, élevé ou modéré.

Secondaires • Focus sur les profils de patients, la non atteinte des cibles LDL C,

• la tolérance des médicaments utilisés,

• La consommation et l’utilisation des ressources de santé,

• l’implémentation des recommandations… -

• Comparer le niveau de risque cardiovasculaire calculé (ESC Score) avec le niveau évalué par le médecin

• Comparer la cible LDL-C considérée par le médecin à celle définie par les recommandations ESC/EAS,

• et comparer la proportion des patients déclarés « Hypercholestérolémie familiale » à celle utilisant les critères de Dutch.

..(11)

Comparaison ESC-EAS/ACC-AHA

Study Population

• The study was implemented in 453 centres in 18 countries

• Location of eligible patients: – 3546 (39.2%) from Asia – 1896 (21.0%) from Latin America – 1890 (20.9%) from Middle East – 881 (9.7%) from Africa – 846 (9.3%) from Eastern Europe

• The largest numbers of patients were from: – India (n=2013) – South Korea (n=1034) – Turkey (n=830) – Mexico (n=622) – Algeria (n=500)

9886 patients screened

727 excluded: • Patient decision 35.7% • Investigator decision 37.6% • Other reasons 26.6%

9159 patients included

9049 eligible patients

109 patients ineligible

OBS14286 – ICLPS 9 May 2017 Patients screened between 3 August 2015 and 31 August 2016 Database was locked on 4 November 2016.

Physician Characteristics (n = 452)

40,5

25,4

13,5

11,7

1,8

4,4

2,7

0 10 20 30 40 50

Cardiologist

Internal medicine

General or…

Endocrinologist

Lipidologist

Other

Several…

Proportion of physicians (%)

Physician specialty Characteristic

Physicians (N=452)

Age (years), mean (SD) 49.0 (9.3)

Years of practice, mean (SD) 22.3 (9.2)

Practice location, n (%) Urban Rural Suburban

385 (85.2)

6 (1.3) 61 (13.5)

Type of practice, n (%) Public hospital Private clinic Office

236 (52.2) 191 (42.3) 88 (19.5)

Guidelines followed, n (%) ACC/AHA1

ESC/EAS2

Other international Local

231 (53.3) 276 (63.7)

23 (5.3) 72 (16.6)

OBS14286 – ICLPS 9 May 2017 ACC, American College of Cardiology; AHA, American Heart Association; EAS, European Atherosclerosis Society; ESC, European Society of Cardiology; LMT, lipid-modifying therapy; SD, standard deviation

61 14%

183 40%

61 14%

115 25%

20 4%

12 3%

Généraliste Cardiologue

Lipidologiste endocrinologue Interniste

Autre spécialité Plusieurs spécialités

5 10%

30 61%

4 8%

9 19%

0 0%

1 2%

Global Algérie

Praticiens

Expérience

Variable Données

manquantes

Valeurs

extrêmes

Moyenne Médiane Ecart type Quartiles

Ancienneté 0 12 à 40 24,3 22 7,1 19 ; 28

L’ancienneté professionnelle varie de 12 à 40 ans, en moyenne 24,3 ± 7,1 ans

Recrutement

• Au total, 608 patients ont été recrutés dont 500 retenus et 108 non retenus, la décision de ne pas retenir étant :

• Une décision du patient pour 16 d’entre eux

• Une décision du médecin pour 54 d’entre eux

• Une autre raison pour 31 d’entre eux

• Non précisé pour 7 d’entre eux.

• Parmi les 500 retenus, 15 ont été déclarés non éligibles.

• L’analyse a porté sur 485 patients éligibles.

Caractéristiques des patients : Algérie vs Global

Syndrome métabolique

IDF

3 42 39 281 120 485

2 28 26 196 78 330 (68%)

Metabolic syndrome† 69 346 291 2522 1361 4589(59.6)

Variable Risque bas Risque modéré Risque élevé Risque très élevé Risque non évalué Total



IDF

3 42 39 281 120 485

2 28 26 196 78 330 (68%)

Diabète 3 29 24 188 72 316 ( 65%)


Diabetes mellitus 69 365 253 2627 1602 4916 (54.3)



Hypertension artérielle 0 27 31 202 99 359 (74%)


IDF

3 42 39 281 120 485

2 28 26 196 78 330 (68%)

Diabète 3 29 24 188 72 316 ( 65%)



Hypertension 47 380 445 3876 1725 6473(71.5)



Hypertension artérielle 0 27 31 202 99 359 (74%)

Tabagisme 0 6 7 140 16 135( 27%)


IDF

3 42 39 281 120 485

2 28 26 196 78 330 (68%)

Diabète 3 29 24 188 72 316 ( 65%)



Hypertension 47 380 445 3876 1725 6473(71.5)

Current smoker 8 69 53 756 238 1124(12.4%)


35,46% (172)

14,84% (68)

6,59% (32) 7,42% (36)

0,41% (2) 5,55% (27)

0

10

20

30

40

50

60

70

80

90

100

RCV

Coronaropathie angioplastie CABG AVC AVC revasc AOMI

Medical History by CV Risk Level

• 3320 (37%) of patients presented with a documented CAD • The most frequent pathologies were previous ACS or MI and previous PCI

• 6.3% of patients had documented cerebrovascular disease (stroke)

• 4.8% of patients had documented PAD

Medical history, n (%) Total

(N=9049)

Cardiovascular risk level

Low (n=139)

Moderate (n=776) High (n=585)

Very-high (n=4842)

Not known (n=2707)

CAD (documented) 3320 (37) 0 0 0 3320 (68.6) 0

Cancer 298 (3.3) 0 (0.0) 25 (3.2) 28 (4.8) 187 (3.9) 58 (2.1)

CKD (GFR <60 mL/min/1.73 m2) 922 (10.2) 2 (1.4) 20 (2.6) 21 (3.6) 821 (17.0) 58 (2.1)

Congestive heart failure 796 (8.8) 1 (0.7) 9 (1.2) 20 (3.4) 717 (14.8) 49 (1.8)

COPD 319 (3.5) 0 (0.0) 10 (1.3) 18 (3.1) 239 (4.9) 52 (1.9)

Neurocognitive disorder 291 (3.2) 0 (0.0) 13 (1.7) 17 (2.9) 224 (4.6) 37 (1.4)

Peripheral artery disease 430 (4.8) 0 0 0 430 (8.9) 0

Stroke (any) 567 (6.3) 0 0 0 567 (11.7) 0

OBS14286 – ICLPS 9 May 2017. ACS, acute coronary syndrome; COPD, chronic obstructive pulmonary disease; GFR, glomerular filtration rate; MI, myocardial infarction PCI, percutaneous coronary intervention

35,46% (172)

14,84% (68)

6,59% (32) 7,42% (36)

0,41% (2) 5,55% (27)

0

10

20

30

40

50

60

70

80

90

100

RCV

Coronaropathie angioplastie CABG AVC AVC revasc AOMI

139 2%

776 9%

585 6%

4842 53%

2707 30%

Risque CV bas Risque CV modéré

Risque CV élevé Risque CV très élevé

Risque CV non évalué

3 0%

42 9%

39 8%

281 58%

120 25%

Global Algérie

Risque cardiovasculaire des patients

Diabète

Diabète

316 (DT2 301) 65%

93 (29,4%)

31(33%)

23 (7%)

18

1

4

2

26 (8%)

59 (19%)

17 (5%)

Effectif

Maladie coronarienne

Antécédent d’intervention coronarienne

Antécédent d’AVC

- Ischémique

- Hémorragique

- Non précisé

Revascularisation de l’artère cérébrale

Antécédent d’AOMI

Ins. rénale chronique

Insuffisance cardiaque congestive

85,12% (269)

72,78% (230)

45,56% (144)

15,50% (49) 11,70% (37)

100% (316)

ADO Metformine Insuline Basale Premix Total

Traitement du diabète

29,43% (93)

21,51% (68) 14,24% (45)

7,27% (23)

27,53% (87)

Hémoglobine glyquée

7% <

7 - 8%

8 - 9%

9% >

NP

Molécules anti hypertensives utilisées

Modalités Risque bas

Risque modéré

Risque élevé

Risque très élevé

Risque non évalué

Total

Effectif 3 42 39 281 120 485

ARAII 0 17 21 122 73 233

Inhibiteur calcique (IC) 0 9 15 98 40 162

IEC 0 6 5 128 20 159

Beta bloquants 0 7 9 160 39 215

Diurétiques 0 6 7 99 50 162

Autre anti hypertenseur 0 1 1 11 4 17

Pas de traitement antihypertenseur 3 14 7 17 18 59

Primary Objective: Percentage of Patients Reaching LDL-C Targets by CV Risk Level

Percentage of patients reaching risk-based LDL-C target decreased with increasing level of CV risk

0

10

20

30

40

50

60

70

80

90

100

Risk-based LDL-C target not reached Risk-based LDL-C target reached

Pro

po

rtio

n o

f p

atie

nts

, % (

95

% C

I) Total (N=6203) Moderate-risk (n=776)

High-risk (n=585) Very-high-risk (n=4842)

OBS14286 – ICLPS 9 May 2017. CI, confidence interval; CV, cardiovascular Patient numbers are based on those in whom CV risk could be assessed at baseline (non-assessable patients excluded from the total population)

32.1

43.9

64.0

37.2 36.0

62.8 56.1

67.9

Primary Objective: Percentage of Patients Reaching LDL-C Targets by CV Risk Level

Algeria

0,0

10,0

20,0

30,0

40,0

50,0

60,0

70,0

80,0

90,0

100,0

Risk-based LDL-C target not reached Risk-based LDL-C target reached

Pro

po

rtio

n o

f p

atie

nts

, % (

95

% C

I) Total (N=362) Moderate-risk (n=42)

High-risk (n=39) Very-high-risk (n=281)

39.5 38.5

71.4

43.1

28.6

56.9 61.5 60.5

Proportions de patients à l’objectif LDL selon les pays

Médecin satisfaitdu résultat

Conditionscliniques du patient

Intolérance Raison économique Total

84,89% (236)

8,99% (25) 6,83% (19)

1,79% (5)

100% (278)

Non prescription d'une statine à forte dose

● Among patients who had tried but did not tolerate previous statin (N=1351), 70.9% had received one statin, 24.6% two statins and 4.4% ≥3 statins

Reasons for Not Receiving High-dose Statin by CV Risk Level

0

10

20

30

40

50

60

70

80

90

100

Physician satisfied with LDL-C levelon current dose regimen

Due to patient’s clinical conditions, higher dose not medically

appropriate

Higher dose regimen and/or higher-intensity statin not tolerated

Cost/price reasons

Reasons for not receiving high-dose statin*

Total (N=6591) Low-risk (n=107) Moderate-risk (n=594) High-risk (n=431) Very-high-risk (n=3329)

14.2

OBS14286 – ICLPS 9 May 2017. *Atorvastatin 40 or 80 mg or rosuvastatin 20 or 40 mg, or highest dose available in the patient’s country.

13.1 7.9 6.7 7.5

10.9 10.8 8.6 8.4 8.9 8.4 8.4 11.1 7.5 6.9

74.9 69.8

78.4 80.0 80.4

% o

f p

atie

nts

LDL-C Level Achieved by CV Risk Level

Under the current LMT, more moderate- (63.3%) than high- (47%) or very-high-risk (28.5%) patients achieved their risk-based target

Low-risk(n=139)

Moderate-risk(n=776)

High-risk(n=585)

Very-high-risk(n=4842)

Not assessable(n=2707)

Pro

po

rtio

n o

f p

ati

en

ts a

ch

ievin

g L

DL

-C

leve

l (%

)

<1.8 mmol/L (70 mg/dL) ≥1.8–<2.6 mmol/L (70–100 mg/dL) ≥2.6–<3.0 mmol/L (100–115 mg/dL)

≥3.0–<3.4 mmol/L (115–130 mg/dL) ≥3.4–<4.1 mmol/L (130–160 mg/dL) ≥4.1 mmol/L (160 mg/dL)

100

80

60

40

20

OBS14286 – ICLPS 9 May 2017. Patient numbers are based on those in whom CV risk could be assessed at baseline

9.4

8.6

15.8

16.5

32.4

17.3

9.1

14.8

12.8

14.6

34.5

14.2

12.1

14.2

10.1

16.6

32.3

14.7

6.4 8.1

8.4

12.0

36.6

28.5

11.3

14.1

11.4

13.6

32.2

17.3

Varia

ble

Modalités Risq

ue

bas

Risque

modér

é

Risqu

e

élevé

Risqu

e très

élevé

Risque

non

évalué

Total

Age Effectif 3 42 39 281 120 485

N=30%

N=24%

>50% of patients at high/very-high calculated risk were estimated to be a lower risk level by physicians

Physician-Estimated versus ESC/EAS Assessment of Patient CV Risk

0

10

20

30

40

50

60

70

80

90

100

Low (n=138) Moderate (n=775) High (n=585) Very-high (n=4835)

Ph

ysic

ian

-est

imat

ed C

V r

isk

(%)

ESC/EAS cardiovascular risk level1

Low Moderate High Very-high

OBS14286 – ICLPS 9 May 2017

11.6

34.4

38.1

15.9

45.7

30.0

18.2

6.5

5.2

26.3

43.7

24.8

2.9

21.7

34.8

40.6

Physician-estimated CV risk:

Algeria

Physician-Estimated versus ESC/EAS Assessment of Patient CV Risk

0

10

20

30

40

50

60

70

80

90

100

Low (n=3) Moderate (n=42) High (n=39) Very-high (n=281)

Ph

ysic

ian

-est

imat

ed C

V r

isk

(%)

ESC/EAS cardiovascular risk level1

Low Moderate High Very-high

15,4

48,8

17,9

17,9

70,8

18,9

7,5 2,8

4,7

42,9

35,7

16,7

33,3

33,3

33,3

Physician-estimated CV risk:

HF Algérie

Etiologie de

l’hyperchole

stérolémie

Effectif 3 42 39 279 120 483 DLCN

Familiale 0 3 1 6 1 11 7

Risque bas Risque

modéré

Risque

élevé

Risque très

élevé

Risque non

évalué

Total

36% des HF diagnostiquées par les médecins n’ont pas de HF selon DCLN

Physician Assessment of FH versus DLCN Criteria Assessment

• 16.3% of patients with FH diagnosed by physicians did not actually have FH according to DLCN criteria (Kappa coefficient 0.222, 95% CI 0.175–0.268)

Pro

po

rtio

n o

f p

atie

nts

(%

)

FH diagnosis by physician

OBS14286 – ICLPS 9 May 2017. DLCN, Dutch Lipid Clinic Network diagnostic criteria

4.4% also had FH by DLCN

76.0% also did not have FH by DLCN

20.7% of patients had FH according to physician assessment

79.3% of patients did not have FH according to physician assessment

■ Agreement between physician assessment and DLCN diagnosis

■ Disagreement between physician assessment and DLCN diagnosis

3.3% had FH by DLCN

Nordestgaard BG et al. Eur Heart J. 2013;34:3478–90a

0

10

20

30

40

50

60

70

80

90

100

No Yes

16.3% did not have FH by DLCN

Intolérance aux statines

Palestine

Causes d’intolérance

Symptômes musculaires

0 1 1 5 2 9

Symptômes Gastro-intes

0 0 1 6 3 10

Autres raisons

1 0 0 0 0 1

NP 0 0 0 2 0 2

Modalités Risque bas Risque modéré Risque élevé Risque très élevé Risque non évalué Total

Intolérance aux statines

Intolérance aux statines, controverses, résistance, reluctance

Toth PP. Am J Cardiovas Drugs 2018

Quelles recommandations ?

Palestine

Physician-Estimated Target Assessment versus ESC/EAS Guideline-Assessed Target

• On average, the LDL-C target assessed by the physician was significantly higher than the target assessed using ESC/EAS guidelines1 (P<0.0001)

– Mean difference between these assessments was higher for physicians who did not follow any guidelines or who followed other international guidelines compared with those who followed ESC/EAS1 or ACC/AHA2 guidelines

52

Guideline followed by investigator

Difference (%) between LDL-C target value assessed by the investigator and target value defined by ESC/EAS guidelines (n=6138)

Overall Mean (SD)

Median (IQR)

12.3 (27.8)

0.7 (0.0, 43.9) Investigator did not follow any guidelines

Mean (IQR) 3.6 (–13.7, 43.9)

Investigator followed other international guidelines

Mean (IQR) 38.9 (0.7, 43.9)

Investigator followed ESC/EAS guidelines

Mean (IQR) 0.7 (0.0, 29.5)

Investigator followed ACC/AHA guidelines

Mean (IQR) 0.7 (0.0, 46.9)

OBS14286 – ICLPS 9 May 2017.

1. Reiner Z et al. Eur Heart J, 2011;32:1769–818; 2. Stone NJ et al. J Am Coll Cardiol, 2014;63:2889–934.

Facteurs associés à la non atteinte de l’objectif LDL -C

Variable Modalités Atteinte cible LDL

Non atteinte

Diabète Pas de diabète

Nombre ECG

Effectif 156 206 316 169

n 136 189 278 157

Nombre d’écho

n 93 128 180 107

Delta +28% +43%

Consommation des ressources en soins

Consommation des ressources en soins

Variable Modalités Atteinte cible LDL

Non atteinte Diabète Pas de diabète

Effectif 156 206 316 169

Nbre sujets hospitalisés 27 23 32 23

Durée des 3 hospitalisations les plus récentes

Effectif 26 19 27 22

M ± ET 13 ±23 5,1 ± 3,7 13,3 ± 22,5 5 ± 2,9

Val extr 1 à 105 1 à 15 1 à 105 1 à 10

Nombre de consultations en urgence

Effectif 134 176 271 146

0 118 157 237 135

1 12 11 24 6

>1 4 8 10 5

Nombre de consultations vers un généraliste

Effectif 111 142 227 109

0 61 85 116 71

1 11 17 25 12

>1 39 40 86 26

Nombre de consultations vers un cardiologue

Effectif 151 199 303 168

0 28 40 71 11

1 11 13 32 10

>1 112 146 200 147

Nombre de consultations vers un autre spécialiste

Effectif 117 155 253 113

0 44 49 57 73

1 8 16 20 12

>1 65 90 176 28

Delta +33% +49%

Vs delta LDL 45% Diabète Global 39%

ICLPS

Palestine

Synthèse

• This registry of 9049 patients receiving LMT in 18 non-Western countries shows that the rate of LDL-C control is suboptimal, particularly in patients at high or very-high CV risk

• An estimated 37.2% (95% CI 36.0–38.4%) of patients achieved LDL-C goals according to ESC/EAS guidelines.

– Rate of patients achieving LDL-C goal decreases with increasing level of CV risk

• Non-achievement of goals was more common in women than men and when other risk factors, excluding diabetes, were present or poorly controlled

• High-dose statins are insufficient to achieve LDL-C goals in many instances

• There is a discrepancy between risk as assessed by physicians and score-calculated risk.

57

OBS14286 – ICLPS 9 May 2017.

Do we reached the LDL target?

• In clinical trials:

meta-analysis (Boekholdt, JACC 2014): 40.4% did not reached an LDL target < 70 mg/dl (1.81 mmol/l)

• In real-life:

DYSIS study (Leiter LA. Diabet Med 2011): 41.3% of statin-treated patients were not at LDL-C goal (> 2.5 mmol/l)

EUROASPIRE III 2006–2007 (n=6588)

• 79% of patients with diabetes were (n=1541) on a statin

• Overall, only 53% of patients with prevalent diabetes reached

the LDL-C target of <100 mg/dl (2.5 mmol/l)

Gyberg V et al. Eur J Prev Cardiol. 2015, 22: 753-61

% of patients achieving LDL-C target:

<1.8 mmol/L

<2.5 mmol/L 0

20

40

60

80

100

No Diabetes (n=4295)

Incident Diabetes (n=752)

Prevalent Diabetes (n=1541)

<3.0 mmol/L

Les Recommandations évoluent, les pratiques…

N= 3x500

Contrôle optimal vs sous optimal

Réponse aux statines : Différences raciales

The Myocardial Infarction Genetics Consortium Investigators. N Engl J Med 2014;371:2072-2082

Naturally occurring mutations that disrupt NPC1L1 function were found to be associated with reduced plasma LDL cholesterol levels (12mg/dl) and a reduced risk of coronary heart disease (53%) (heterozygous).

Inactivating Mutations in NPC1L1 and Protection from Coronary Heart Disease

Preuves génétiques: Inactivating mutations in NPC1L1 and protection from CHD

LDL Cholesterol and Coronary Heart Disease among Subjects by PCSK9142X or PCSK9679X Allele

PCSK9142X or PCSK9679X

Cohen NEJM 2006; 354:1264-72

Co

ron

ary

Heart

Dis

ease (

%)

No Yes

P=0.008

12

8

4

0

88%

Feuille de route

21ème congrès sadiab 2019 - sadiab-dz.comperipheral artery disease 430 (4.8) 0 0 0 430 (8.9) 0...

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