IMPLEMENTATIE ESC GUIDELINES 2013 LIPIDEN IN PRAKTIJK Casuistiek
• Dr. Celen Hendrik • Cardiologie • Heilig Hart
Ziekenhuis Leuven
• 6/3/2013
IMPLEMENTATIE ESC GUIDELINES LIPIDEN 2010 IN PRAKTIJK
• • • •
Risicofactoren, Lipoproteïnes en Atherogenese Werkingsmechanisme van hyolipimiërende farmaca Richtlijnen Casuistiek
Viscerale obesitas en lipoproteïnes
Lower Cholesterol Levels Associated The Framingham Heart Study
CHD Incidence per 1000
150 125 100 75 50 25 0 ≤ 204
Castelli WP. Am J Med. 1984;76:4-12.
205-23 4
235-26 265-29 4 4
≥ 295
Serum Cholesterol (mg/100 mL)
Atherogene balans
Atherogenic and anti-atherogenic lipoproteins
From the liver
Back to the liver “Reverse cholesterol transport”
TG C
TG
apoB
VLDL
C
C apoB IDL
C apoB
apoB
large buoyant LDL small dense LDL
Atherogenic
C
HDL
Anti-atherogenic
apo A-I
Lipoprotein (a) Homocysteine IL-6 TC LDLC sICAM-1 SAA Apo B TC:HDLC hs-CRP hs-CRP + TC:HDLC 0 1.0 2.0 4.0 6.0
Relative Risk of Future Cardiovascular Events Ridker et al, N Engl J Med 2000;342:836-843
Risk Factors for Future Cardiovascular Events: Women’s Health Study
LDL Cholesterol
• Hoeksteen van de lipidentherapie • Associatie met pathogenese atherosclerose en cardiale eindpunten • 10% stijging resulteert in 20% stijging in CVrisico1
•
bevat vooral cholesterolester en veel lipoproteine B
•
opname door hepatocyten en non hepatisch weefsel
•
dense smalle LDL cholesterolpartikels
1. Wood D et al. Atherosclerosis. 1998;140:199-270. 2. National Centre for Health Statistics. National Health and Nutrition Examination Survey (III), 1994. 3. Jacobson TA, et al. Arch Intern Med. 2000;160:1361-1369.
LDL-C Lowering With Statins: Reduced CHD Events Secondary Prevention
25
LIPID-PL
Events (%)
20
4S-Rx
15
CARE-PL
CARE-Rx 10
LIPID-Rx
5
WOSCOPS-Rx
WOSCOPS-PL
AFCAPS-Rx AFCAPS-PL
0 50
4S-PL
Primary Prevention
70
90
110
130
150
170
190
LDL Cholesterol (mg/dL) Adapted from Illingworth DR. Med Clin North Am. 2000;84:23-42.
210
HDL Cholesterol
• Laag HDL cholesterol onafhankelijke predictor voor CHD1 • Hoe lager het HDL-cholesterol, hoe hoger risico CHD2 • Laag HDL is gedefinieerd als < 40 mg/dL1 • HDL cholesterol is laag als triglyceridengehalte hoog is 1. NCEP, Adult Treatment Panel III. JAMA. 2001;285:2486-2497. 2. Wood D, et al. Atherosclerosis. 1998;140:199-270.
Low HDL Cholesterol Levels Increase CHD Risk Even When TC Is Normal: Framingham Heart Study 0 12.5 1
14 14-y incidence rates for CHD (%)
12 10
1 11.9
1. 91
4 11.2
9.05
10.7 6.6 5.53
6.56
8
3.83
4.85
6 4
4.67
4.15
3.77
2 0
<40
40-49 50-59 ≥60 HDL cholesterol (mg/dL)
Risk of CHD by HDL cholesterol and TC levels; subjects aged 48-83 y. Castelli WP et al. JAMA. 1986;256:2835-2838.
2.78
≥260 230-259 200-229 TC <200 (mg/dL) 2.06
Cholesterol Homeostasis ATHEROGENIC DYSLIPIDEMIA ATHEROGENIC DYSLIPIDEMIA
ATHEROGENIC DYSLIPIDEMIA : PLAQUE PROGRESSION
Type 2 Diabetes Mixed Hyperlipidemia Metabolic Syndrome Hypercholesterolemia Renal Disease FH Apo.B LPs Anti-atherogenic HDL ApoAI
Atherogenic ApoB100containing LPs
• • • •
LDL-C : HDL-C > 3:1
VLDL VLDL Remnants IDL LDL; Dense LDL
HDL Apo AI Plaque Cholesterol content
=
Influx
Cholesterolrich plaque
Cholesterol Efflux Plaque Inflammation Fragilisation
=
Cardiovascular Events
ATHEROSCLEROTIC PLAQUE STABILISATION
Influx
Apo.B LPs
Cholesterol
HDL Apo AI Plaque Cholesterol content
Cholesterolrich plaque
Efflux
=
Plaque stability
=
Cardiovascular Events
Een deel van het residuele risico : De atherogene triade Klein en dense LDL
Athertogene Lipiden Triade
↑ TG rijk aan Lp
↑ Non-HDL-C (maar apoB)
Meer atherogeen !
↓ HDL-C Frequen geobserveerd :
type 2 diabetes (T2D) patiënten met MetS patiënten met nierinsufficiëntie ziekten van het auto-immuunstelsel With the courtesy of Prof. Michel Farnier, Dijon.
De dosering van LDL-C is misleidend LDL-C: 114 mg/dl Triglyceriden: 150 mg/dL
LDL-C: 114 mg/dl Triglyceriden: 198 mg/dL
Apo B: 0,9 g/L
Apo B: 1,3 g/L
1 apo B per LDL-partikel Presented by M. Langlois Lipid Club Dec 2011
Non-HDL-C Het bepalen van non-HDL-C (TC - HDL-C) bevat alle atherogene lipoproteïnes : VLDL, IDL, LDL
Dyslipidaemie •hypercholesterolaemie : LDL receptorgenmutatie ? •hypercholesterolaemie met laag HDL •Gemengde dyslipidaemie :apo B overproductie? •hypertriglyceridaemie : LPL deficientie •metabool syndroom •geïsoleerd laag HDLfamiliaal hypoalfalipoporteïnaemie •normaal lipidenprofiel en CVD ?
IMPLEMENTATIE ESC GUIDELINES LIPIDEN Casuistiek
• • • •
Risicofactoren, Lipoproteïnes en Atherogenese Werkingsmechanisme van hyolipimiërende farmaca Richtlijnen Casuistiek
Liver
Statin
Endogenous Cholesterol Synthesis
LDL-Receptors
VLDL-LDL-Cholesterol HDL
Atherogenic VLDL, IDL,LDL
HDL
Atherogenic VLDL, IDL, LDL
ApoB LPs Atheroma
Influx
HDL Plaque Cholesterol Content
Cholesterol Efflux
=
Plaque Stability
=
Cardiovascular Events
Sposito, Chapman ATVB 2002; 22 : 1524-34
Two sources of Cholesterol VLDL
IDL
LDL
Synthesis 800mg/day Absorption (700mg/day)
BILIARY CHOLESTEROL (1000 mg/day
) INTESTINE
DIETARY CHOLESTEROL (300 - 700 mg/day)
Excretion
IMPLEMENTATIE ESC GUIDELINES LIPIDEN Casuistiek
• • • •
Risicofactoren, Lipoproteïnes en Atherogenese Werkingsmechanisme van hyolipimiërende farmaca Richtlijnen Casuistiek
De ESC-richtlijnen voor de behandeling van dyslipidemie definiëren 4 risiconiveaus
Reiner & al. ESC/EAS Guidelines for the management of dyslipidaemias 2011 Adapted O. Descamps Louvain Médical 2012
Aanbevelingen voor dyslipidemieën (ESC 2011)
4 risico niveaus
3 LDL niveaus < 115 < 100 < 70
Non-HDL
Reiner &AL. ESC/EAS Guidelines for the management of dyslipidaemias 2011 Adapted O. Descamps Louvain Médical 2012
Aanbevelingen ADA Aanbevolen waarden voor metabool syndroom/diabetes en lipidenafwijkingen
Patiënten met zeer hoog risico +++ In secundaire preventie of diabetes + CV risicofactoren (RF) Patiënten met hoog risico ++ In primaire preventie, zonder diabetes maar > 2 RF of diabetes zonder RF
LDL (mg/dL)
Non- HDL (mg/dL)
Apo B (mg/dL)
<70
< 100
< 80
< 100
< 130
< 90
Brunzell, Diabetes Care 2008 FR = Facteurs de risque
EVOLUTIE RICHTLIJNEN
Populatie afhankelijk
SCORE : HDL
HDL (mg/dl)
man
vrouw
30
X 1.8
X 1.3
X 1.5
X 1.1
46
X 1.2
X1
54
X1
X 0.9
62
X 0.8
X 0.8
70
X 0.7
X 0.7
38
HDL
Factoren die het risico verhogen Familiaal vroegtijdig CV ziekten (man < 55j, vrouw < 60j) Risico x 1.7 vrouw x 2.0 man •
<48j, relatief risico
In the overall population, the primary endpoint of major CV events was reduced by 8% (NS)
Proportion with event (%)
100
20
80
Placebo
10
Fenofibrate
60 0 0
1
2
3
4
5
6
7
8
40 0.92 (95% CI 0.79-1.08), p=0.32
20
0 0 No. At Risk Fenofibrate Placebo
1
2
3
4
6
7
8
1160 1161
412 395
249 245
137 131
Years 2765 2753
2644 2634
2565 2528
2485 2442
1981 1979
Major CV events defined as CV death, nonfatal MI and nonfatal stroke ACCORD Study Group. N Engl J Med. 2010; 362(17):1563-74.
5
Lipanthyl significantly reduced CV events in the elevated TG + low HDL-C subgroup by 31%
In patients with TG ≥204 mg/dL and HDL-C ≤34 mg/dL 18
Proportion with event (%)
16
17.32%
-31% p=0.03
14 12
12.37%
10 8 6
Number needed to treat (NNT) for 5 years to prevent one CV event
20
4 2 0
Simvastatin
Simvastatin + Lipanthyl
The primary endpoint of major CV events (CV death, nonfatal MI and nonfatal stroke) was not reduced significantly in the overall population (HR=0.92, 95% CI 0.79-1.08, p=0.32)
ACCORD Study Group. N Engl J Med. 2010; 362(17):1563-74. Elam MB et al. AHA 2010. Presentation 19724.
SCORE enDIABETES? • •
5X VROUWEN 3X MANNEN
•
UKPDS RISC ENGINE
Am Heart J 2001; 141(6):957-963
W OS CA COP RE
NC 4S EP
LR CP CPT
Clinical Trials and Recent Patterns in the Use of Statins National Ambulatory Medical Care Survey
• • • •
Chapter 1 : Generic + ZOCOR Prescribed freely without any control ( ~ cheap products ) IndicaAon : PaAents with Hypercholesterolemia Products : Zocor, Simva Generic, Prava Generic, Pravasine, atorva Generic, Totalip
Chapter 2 : Original StaAns • Prescribed in B with a posteriori control • Reimbursement: PaAents not at goal aKer 3 months on cheap staAns • Products : AtorvastaAn 10,20,40,80 mg and RosuvastaAn 10,20,40 mg Chapter 4 : EZETROL & INEGY • Prescribed in Bf with a priori control through the medical advisor • General PracAAoner needs a posiAve advice of the Specialist • IndicaAon : PaAents at goal aKer 3 months aKer staAn therapy • Products : Ezetrol and Inegy 10/20, 10/40, 10/80 mg
