Aterosclerosi, Colesterolo, Statine e Rischio … · Aterosclerosi, Colesterolo, Statine e Rischio...

1
L’Aterosclerosi è una condizione associata a Malattia CV, in particolar modo a quella Coronarica nella maggior parte dei pazienti, ed è una delle principali cause di morte nei paesi sviluppati. La proiezione all’anno 2020 del World Healt Report 2002 della World Healt Organization prevede vi saranno circa 4 milioni di morti (7% della mortalità totale) causate da elevati valori del colesterolo se non si metteranno in atto delle misure adeguate. L’Aterosclerosi, spesso combinata a Malattia CV, è presente in molte manifestazioni cliniche che includono: Patologia Coronarica: Angina pectoris, Infarto miocardico, Morte cardiaca improvvisa Patologia Cerebrale: Attacchi ischemici transitori (TIA), Stroke Patologia Vascolare Periferica: Claudicatio intermittens, Gangrena La manifestazione clinica più importante in termini di morbilità e mortalità è la Patologia Coronarica. Con 4 milioni di morti ogni anno, maggior causa di morte in Europa, la Malattia CV è associata ad elevati valori di colesterolo. Vari Trials hanno evidenziato che identificare e diminuire il valore di questo fattore di rischio CV può aiutare a ridurre le sequele della Malattia CV. Relationship Between Cholesterol and CHD Risk: Framingham Study Relationship Between Cholesterol and Relationship Between Cholesterol and CHD Risk: Framingham Study CHD Risk: Framingham Study 0 25 50 75 100 125 150 <204 (<5.3) 205-234 (5.3-6.1) 235-264 (6.1-6.8) 265-294 (6.8-7.6) >295 (>7.6) CHD incidence per 1000 Serum total cholesterol, mg/dL (mmol/L) 0 25 50 75 100 125 150 <204 (<5.3) 205-234 (5.3-6.1) 235-264 (6.1-6.8) 265-294 (6.8-7.6) >295 (>7.6) CHD incidence per 1000 Serum total cholesterol, mg/dL (mmol/L) Global Burden of Cardiovascular Disease Global Burden of Cardiovascular Disease Global Burden of Cardiovascular Disease In 2002: CVD contributed to approximately a third of all global deaths (17 million) 80% of burden is in low and middle-income countries By 2020: CHD and stroke will become the leading cause of death and disability worldwide Mortality from CVD will increase to 20 million Clinical care of CVD is costly and prolonged Cholesterol: A Modifiable Risk Factor Cholesterol: A Modifiable Risk Factor Cholesterol: A Modifiable Risk Factor Plasma cholesterol at levels >200 mg/dL cause 4.4 million deaths a year 1 Incidence of plasma cholesterol >200 mg/dL in: 51% (107 million) adults in the USA 2 58% of patients with established CHD in EUROASPIRE II 3 10% reduction in plasma cholesterol results in: 15% reduction in CHD mortality (p<0.001) 11% reduction in total mortality (p<0.001) 4 LDL-C is a major target to prevent CHD 1. International CVD Statistics 2005 AHA; 2. Heart and Stroke Statistical Update 2004 AHA; 3. EUROASPIRE II Study Group. Eur Heart J 2001;22:554-572; 4. Gould AL et al. Circulation1998;97:946952. Pathogenesis of Atherosclerotic Plaques Pathogenesis of Atherosclerotic Plaques Pathogenesis of Atherosclerotic Plaques Protective response results in production of cellular adhesion molecules Monocytes and T lymphocytes attach to ‘sticky’ surface of endothelial cells Migrate through arterial wall to subendothelial space Lipid-rich foam cells Endothelial damage Macrophages take up oxidised LDL-C Fatty streak and plaque Protective response results in production of cellular adhesion molecules Monocytes and T lymphocytes attach to ‘sticky’ surface of endothelial cells Migrate through arterial wall to subendothelial space Lipid-rich foam cells Endothelial damage Macrophages take up oxidised LDL-C Fatty streak and plaque Upregulation of endothelial adhesion molecules Increased endothelial permeability Migration of leucocytes into the artery wall Leucocyte adhesion Lipoprotein infiltration Increased endothelial permeability Migration of leucocytes into the artery wall Leucocyte adhesion Lipoprotein infiltration Endothelial Dysfunction in Atherosclerosis Endothelial Dysfunction in Atherosclerosis Formation of foam cells Adherence and entry of leucocytes Activation of T cells Migration of smooth muscle cells Adherence and aggregation of platelets Formation of foam cells Adherence and entry of leucocytes Activation of T cells Migration of smooth muscle cells Adherence and aggregation of platelets Fatty Streak Formation in Fatty Streak Formation in Atherosclerosis Atherosclerosis Formation of the fibrous cap Accumulation of macrophages Formation of necrotic core Formation of the fibrous cap Accumulation of macrophages Formation of necrotic core Formation of the Complicated Atherosclerotic Plaque Formation of the Complicated Atherosclerotic Plaque Haemorrhage from plaque microvessels Rupture of the fibrous cap Thinning of the fibrous cap Haemorrhage from plaque microvessels Rupture of the fibrous cap Thinning of the fibrous cap Rupture of the fibrous cap Thinning of the fibrous cap The Unstable Atherosclerotic Plaque The Unstable Atherosclerotic Plaque Intraluminal thrombus Intraplaque thrombus Lipid pool Intraluminal thrombus Intraplaque thrombus Lipid pool Atherosclerotic Plaque Rupture and Atherosclerotic Plaque Rupture and Thrombus Formation Thrombus Formation Clinical Manifestations of Atherosclerosis Clinical Manifestations of Clinical Manifestations of Atherosclerosis Atherosclerosis Coronary heart disease Angina pectoris, myocardial infarction, sudden cardiac death, congestive heart failure (CHF), and arrhythmias Cerebrovascular disease Transient ischaemic attack, stroke Peripheral vascular disease Intermittent claudication, gangrene, cold feet, painful feet, impotence Benefits of Cholesterol Lowering Benefits of Cholesterol Lowering Benefits of Cholesterol Lowering Meta-analysis of 38 primary and secondary intervention trials % in cholesterol reduction Total mortality ( p =0.004) CHD mortality ( p =0.012) Mortality log odds ratio 0 4 8 12 16 20 24 28 32 36 -1.0 -0.8 -0.6 -0.4 -0.2 -0.0 40 Meta-analysis of 38 primary and secondary intervention trials % in cholesterol reduction Total mortality ( p =0.004) CHD mortality ( p =0.012) Mortality log odds ratio 0 4 8 12 16 20 24 28 32 36 -1.0 -0.8 -0.6 -0.4 -0.2 -0.0 40 Total mortality ( p =0.004) CHD mortality ( p =0.012) Mortality log odds ratio 0 4 8 12 16 20 24 28 32 36 -1.0 -0.8 -0.6 -0.4 -0.2 -0.0 40 Gould AL et al. Circulation. 1998;97:946-952. Relationship Between Changes in LDL-C and HDL-C Levels and CHD Risk Relationship Between Changes in Relationship Between Changes in LDL LDL- C and HDL C and HDL- C Levels and CHD Risk C Levels and CHD Risk 1% decrease in LDL-C reduces CHD risk by 1% 1% increase in HDL-C reduces CHD risk by 3% Is Lower Better? Relationship between LDL-C and CV Event Rate Is Lower Better? Relationship between Is Lower Better? Relationship between LDL LDL-C and CV Event Rate C and CV Event Rate LDL-C achieved mg/dL (mmol/L) WOSCOPS – Pl AFCAPS - Pl ASCOT - Pl AFCAPS - Rx WOSCOPS - Rx ASCOT - Rx 4S - Rx HPS - Pl LIPID - Rx 4S - Pl CARE - Rx LIPID - Pl CARE - Pl HPS - Rx 0 5 10 15 20 25 30 40 (1.0) 60 (1.6) 80 (2.1) 100 (2.6) 120 (3.1) 140 (3.6) 160 (4.1) 180 (4.7) E v e n t r a t e ( %) 6 Secondary Prevention Primary Prevention Rx - Statin therapy Pl – Placebo Pra – pravastatin Atv - atorvastatin 200 (5.2) PROVE-IT - Pra PROVE-IT – Atv TNT – Atv10 TNT – Atv80 LDL-C achieved mg/dL (mmol/L) WOSCOPS – Pl AFCAPS - Pl ASCOT - Pl AFCAPS - Rx WOSCOPS - Rx ASCOT - Rx 4S - Rx HPS - Pl LIPID - Rx 4S - Pl CARE - Rx LIPID - Pl CARE - Pl HPS - Rx 0 5 10 15 20 25 30 40 (1.0) 60 (1.6) 80 (2.1) 100 (2.6) 120 (3.1) 140 (3.6) 160 (4.1) 180 (4.7) E v e n t r a t e ( %) 6 Secondary Prevention Primary Prevention Rx - Statin therapy Pl – Placebo Pra – pravastatin Atv - atorvastatin 200 (5.2) PROVE-IT - Pra PROVE-IT – Atv TNT – Atv10 TNT – Atv80 Design of Key Statin Trials (2) Design of Key Statin Trials (2) Design of Key Statin Trials (2) atorva 10 mg od Low/average 3.4 (130) 10,305 40-79 yrs >3 risk factors ALLHAT-LLT9 prava 40 mg od Hypertension Some CVD 10,355 >55 yrs Average 3.8 (146) 4.8 Statin CVD/risk factors Patients age Mean LDL-C mmol/L (mg/dL) Follow-up (years) Study CARDS 10 atorva 10 mg od Diabetes + 1 other risk factor 2838 40-75 yrs Low/average 3.0 (115) 4.0 3.3 ASCOT-LLA8 PROVE-IT 11 atorva 80 mg prava 40 mg od Yes 4162 >18 yrs Low/average 2.7 (106) 3.0 TNT12 Yes 10,001 35-75 yrs Low/average 2.5 (98) 4.9 atorva 10 mg atorva 80 mg od 1. 4S Study Group. Lancet 1994;344:13831389. 2. Shepherd J et al. N Engl J Med1995;333:13011307. 3. Sacks FM et al. N Engl J Med. IDEAL 13 Yes MI 8888 <80 yrs Low/average 3.1 (121) 4.8 atorva 80 mg simva 20 mg od Design of Key Statin Trials (1) Design of Key Statin Trials (1) Design of Key Statin Trials (1) 4S 1 WOSCOPS 2 CARE 3 LIPID 4 AFCAPS/ TexCAPS 5 simva 20 mg od prava 40 mg od prava 40 mg od prava 40 mg od lova 40 mg od Yes No MI, angina (5% ) Yes Yes Low HDL-C No CHD 5.4 4.9 5.0 6.1 5.2 4444 35–70 yrs 6595 male only 45–64 yrs 4159 21–75 yrs 9014 31–75 yrs 6605 45–73 yrs Raised 4.9 (188) Raised 5.0 (192) Low/average 3.6 (139) Average 3.8 (147) Average 3.9 (150) Statin CVD/risk factors Patients age Mean LDL-C mmol/L (mg/dL) Follow-up (years) Study HPS6 Yes simva 40 mg od 20,536 40-80 yrs Low/average 3.4 (130) 5.0 5804 prava 3.2 Average Yes Summary Summary Summary Atherosclerosis is associated with CVD, which is a major cause of death in developed countries Dyslipidaemia, in particular elevated LDL-C and lowHDL-C, is associated with increased risk for CVD Large statin trials have shown that the lower the level of LDL-C achieved the greater the reduction in CV events Guidelines recommend lipid levels to reduce the morbidity and mortality caused by dyslipidaemia, and proposed recommendations suggest even more Aterosclerosi, Colesterolo, Statine e Rischio Cardiovascolare 1 Greco Eugenio - 2 Greco Raffaella 1 Departement of Internal Medicine, Institute Ninetta Rosano-Clinica Tricarico, Belvedere M.mo (CS) - 2 Scientific Institute Ospedale San Raffaele, Milan - ITALY

Transcript of Aterosclerosi, Colesterolo, Statine e Rischio … · Aterosclerosi, Colesterolo, Statine e Rischio...

Page 1: Aterosclerosi, Colesterolo, Statine e Rischio … · Aterosclerosi, Colesterolo, Statine e Rischio Cardiovascolare 1 Greco Eugenio - 2 Greco Raffaella 1 Departement of Internal Medicine,

LL’’ AAtteerroosscclleerroossii èè uunnaa ccoonnddiizziioonnee aassssoocciiaattaa aa MMaallaattttiiaa CCVV,, iinn ppaarrttiiccoollaarr mmooddoo aa qquueell llaa CCoorroonnaarriiccaa nneell llaa mmaaggggiioorr ppaarrttee ddeeii ppaazziieennttii ,, eedd èè uunnaa ddeell llee pprriinncciippaall ii ccaauussee ddii mmoorrttee nneeii ppaaeessii ssvvii lluuppppaattii.. LLaa pprrooiieezziioonnee aall ll ’’ aannnnoo 22002200 ddeell WWoorrlldd HHeeaalltt RReeppoorrtt 22000022 ddeell llaa WWoorrlldd HHeeaalltt OOrrggaanniizzaattiioonn pprreevveeddee vvii ssaarraannnnoo cciirrccaa 44 mmii ll iioonnii ddii mmoorrttii ((77%% ddeell llaa mmoorrttaall ii ttàà ttoottaallee)) ccaauussaattee ddaa eelleevvaattii vvaalloorrii ddeell ccoolleesstteerroolloo ssee nnoonn ssii mmeetttteerraannnnoo iinn aattttoo ddeell llee mmiissuurree aaddeegguuaattee.. LL’’ AAtteerroosscclleerroossii,, ssppeessssoo ccoommbbiinnaattaa aa MMaallaattttiiaa CCVV,, èè pprreesseennttee iinn mmoollttee mmaannii ffeessttaazziioonnii ccll iinniicchhee cchhee iinncclluuddoonnoo::

•• PPaattoollooggiiaa CCoorroonnaarriiccaa:: AAnnggiinnaa ppeeccttoorriiss,, IInnffaarrttoo mmiiooccaarrddiiccoo,, MMoorrttee ccaarrddiiaaccaa iimmpprroovvvviissaa •• PPaattoollooggiiaa CCeerreebbrraallee:: AAttttaacccchhii iisscchheemmiiccii ttrraannssiittoorrii ((TTIIAA)),, SSttrrookkee •• PPaattoollooggiiaa VVaassccoollaarree PPeerrii ffeerriiccaa:: CCllaauuddiiccaattiioo iinntteerrmmiitttteennss,, GGaannggrreennaa

LLaa mmaannii ffeessttaazziioonnee ccll iinniiccaa ppiiùù iimmppoorrttaannttee iinn tteerrmmiinnii ddii mmoorrbbii ll ii ttàà ee mmoorrttaall iittàà èè llaa PPaattoollooggiiaa CCoorroonnaarriiccaa.. CCoonn 44 mmii ll iioonnii ddii mmoorrttii ooggnnii aannnnoo,, mmaaggggiioorr ccaauussaa ddii mmoorrttee iinn EEuurrooppaa,, llaa MMaallaattttiiaa CCVV èè aassssoocciiaattaa aadd eelleevvaattii vvaalloorrii ddii ccoolleesstteerroolloo.. VVaarrii TTrriiaallss hhaannnnoo eevviiddeennzziiaattoo cchhee iiddeennttii ff iiccaarree ee ddiimmiinnuuiirree ii ll vvaalloorree ddii qquueessttoo ffaattttoorree ddii rriisscchhiioo CCVV ppuuòò aaiiuuttaarree aa rriidduurrrree llee sseeqquueellee ddeell llaa MMaallaattttiiaa CCVV..

Relationship Between Cholesterol and CHD Risk: Framingham Study

Relationship Between Cholesterol and Relationship Between Cholesterol and

CHD Risk: Framingham StudyCHD Risk: Framingham Study

0

25

50

75

100

125

150

<204

(<5.3)

205-234

(5.3-6.1)

235-264

(6.1-6.8)

265-294

(6.8-7.6)

>295

(>7.6)

CHD incidence per 1000

Serum total cholesterol, mg/dL (mmol/L)

0

25

50

75

100

125

150

<204

(<5.3)

205-234

(5.3-6.1)

235-264

(6.1-6.8)

265-294

(6.8-7.6)

>295

(>7.6)

CHD incidence per 1000

Serum total cholesterol, mg/dL (mmol/L)

Global Burden of Cardiovascular DiseaseGlobal Burden of Cardiovascular DiseaseGlobal Burden of Cardiovascular Disease

In 2002:

� CVD contributed to approximately a third of all global deaths (17 million)

� 80% of burden is in low and middle-income countries

By 2020:

� CHD and stroke will become the leading cause of death and disability worldwide

� Mortality from CVD will increase to 20 million

Clinical care of CVD is costly and prolonged

Cholesterol: A Modifiable Risk FactorCholesterol: A Modifiable Risk FactorCholesterol: A Modifiable Risk Factor

� Plasma cholesterol at levels >200 mg/dL cause 4.4 million deaths a year1

� Incidence of plasma cholesterol >200 mg/dL in:

�51% (107 million) adults in the USA2

�58% of patients with established CHD in EUROASPIRE II3

� 10% reduction in plasma cholesterol results in:

�15% reduction in CHD mortality (p<0.001)

�11% reduction in total mortality (p<0.001)4

� LDL-C is a major target to prevent CHD

1. International CVD Statistics 2005 AHA;

2. Heart and Stroke Statistical Update 2004 AHA;

3. EUROASPIRE II Study Group. Eur Heart J 2001;22:554-572; 4. Gould AL et al. Circulation 1998;97:946–952.

Pathogenesis of Atherosclerotic PlaquesPathogenesis of Atherosclerotic PlaquesPathogenesis of Atherosclerotic Plaques

Protective response results in production of cellular adhesion molecules

Monocytes and T lymphocytes attach to ‘sticky’ surface of endothelial cells

Migrate through arterial wall to subendothelial space

Lipid-rich foam cells

Endothelial damage

Macrophages take up oxidised LDL-C

Fatty streak and plaque

Protective response results in production of cellular adhesion molecules

Monocytes and T lymphocytes attach to ‘sticky’ surface of endothelial cells

Migrate through arterial wall to subendothelial space

Lipid-rich foam cells

Endothelial damage

Macrophages take up oxidised LDL-C

Fatty streak and plaque

Upregulation of endothelial

adhesion molecules

Increased endothelial

permeability

Migration of leucocytes

into the artery wall

Leucocyte adhesion

Lipoprotein infiltration

Increased endothelial

permeability

Migration of leucocytes

into the artery wall

Leucocyte adhesion

Lipoprotein infiltration

Endothelial Dysfunction in AtherosclerosisEndothelial Dysfunction in Atherosclerosis

Formation of foam

cells

Adherence and entry

of leucocytes

Activation of T cells

Migration of smooth

muscle cells

Adherence and

aggregation of platelets

Formation of foam

cells

Adherence and entry

of leucocytes

Activation of T cells

Migration of smooth

muscle cells

Adherence and

aggregation of platelets

Fatty Streak Formation in Fatty Streak Formation in

AtherosclerosisAtherosclerosis

Formation of

the fibrous cap

Accumulation of

macrophages

Formation of

necrotic core

Formation of

the fibrous cap

Accumulation of

macrophages

Formation of

necrotic core

Formation of the Complicated Atherosclerotic PlaqueFormation of the Complicated Atherosclerotic Plaque

Haemorrhage

from plaque

microvessels

Rupture of the

fibrous cap

Thinning of the

fibrous cap

Haemorrhage

from plaque

microvessels

Rupture of the

fibrous cap

Thinning of the

fibrous cap

Rupture of the

fibrous cap

Thinning of the

fibrous cap

The Unstable Atherosclerotic PlaqueThe Unstable Atherosclerotic Plaque

Intraluminal thrombus

Intraplaque thrombus

Lipid pool

Intraluminal thrombus

Intraplaque thrombus

Lipid pool

Atherosclerotic Plaque Rupture and Atherosclerotic Plaque Rupture and

Thrombus FormationThrombus Formation

Clinical Manifestations of Atherosclerosis

Clinical Manifestations of Clinical Manifestations of

AtherosclerosisAtherosclerosis

�Coronary heart disease

�Angina pectoris, myocardial infarction, sudden cardiac death, congestive heart failure (CHF), and arrhythmias

�Cerebrovascular disease

�Transient ischaemic attack, stroke

�Peripheral vascular disease

�Intermittent claudication, gangrene, cold feet, painful feet, impotence

B e n e f i t s o f C h o le s te r o l L o w e r in gB e n e f it s o f C h o le s t e r o l L o w e r in gB e n e f it s o f C h o le s t e r o l L o w e r in g

M e ta -a n a ly s is o f 3 8 p r im a ry a n d s e c o n d a r y in te r v e n t io n t r ia ls

% in c h o le s te r o l r e d u c t io n

T o t a l m o r t a l i ty ( p = 0 .0 0 4 )

C H D m o r t a li t y ( p = 0 .0 1 2 )

Mortality log odds ratio

0 4 8 1 2 1 6 2 0 2 4 2 8 3 2 3 6-1 .0

- 0 .8

- 0 .6

- 0 .4

- 0 .2

- 0 .0

4 0

M e ta -a n a ly s is o f 3 8 p r im a ry a n d s e c o n d a r y in te r v e n t io n t r ia ls

% in c h o le s te r o l r e d u c t io n

T o t a l m o r t a l i ty ( p = 0 .0 0 4 )

C H D m o r t a li t y ( p = 0 .0 1 2 )

Mortality log odds ratio

0 4 8 1 2 1 6 2 0 2 4 2 8 3 2 3 6-1 .0

- 0 .8

- 0 .6

- 0 .4

- 0 .2

- 0 .0

4 0

T o t a l m o r t a l i ty ( p = 0 .0 0 4 )

C H D m o r t a li t y ( p = 0 .0 1 2 )

Mortality log odds ratio

0 4 8 1 2 1 6 2 0 2 4 2 8 3 2 3 6-1 .0

- 0 .8

- 0 .6

- 0 .4

- 0 .2

- 0 .0

4 0

G o u ld A L e t a l . C ir c u la t io n . 1 9 9 8 ;9 7 :9 4 6 -9 5 2 . R e l a t i o n s h i p B e t w e e n C h a n g e s i n

L D L - C a n d H D L - C L e v e l s a n d C H D R i s k

R e l a t i o n s h i p B e t w e e n C h a n g e s i n R e l a t i o n s h i p B e t w e e n C h a n g e s i n

L D LL D L -- C a n d H D LC a n d H D L -- C L e v e l s a n d C H D R i s kC L e v e l s a n d C H D R i s k

1 % d e c r e a s ei n L D L - C r e d u c e s

C H D r i s k b y1 %

1 % i n c r e a s ei n H D L - C r e d u c e s

C H D r i s k b y3 %

Is Lower Better? Relationship between LDL-C and CV Event Rate

Is Lower Better? Relationship between Is Lower Better? Relationship between

LDLLDL--C and CV Event RateC and CV Event Rate

LDL-C achieved mg/dL (mmol/L)

WOSCOPS –Pl

AFCAPS - Pl

ASCOT - Pl

AFCAPS - Rx WOSCOPS - Rx

ASCOT - Rx

4S - Rx

HPS -Pl

LIPID - Rx

4S - Pl

CARE - Rx

LIPID - Pl

CARE - Pl

HPS - Rx

0

5

10

15

20

25

30

40(1.0)

60(1.6)

80(2.1)

100(2.6)

120(3.1)

140(3.6)

160(4.1)

180(4.7)

Event rate (%)

6

Secondary Prevention

Primary Prevention

Rx - Statin therapyPl –PlaceboPra –pravastatinAtv - atorvastatin

200(5.2)

PROVE-IT -Pra

PROVE-IT –Atv

TNT –Atv10

TNT –Atv80

LDL-C achieved mg/dL (mmol/L)

WOSCOPS –Pl

AFCAPS - Pl

ASCOT - Pl

AFCAPS - Rx WOSCOPS - Rx

ASCOT - Rx

4S - Rx

HPS -Pl

LIPID - Rx

4S - Pl

CARE - Rx

LIPID - Pl

CARE - Pl

HPS - Rx

0

5

10

15

20

25

30

40(1.0)

60(1.6)

80(2.1)

100(2.6)

120(3.1)

140(3.6)

160(4.1)

180(4.7)

Event rate (%)

6

Secondary Prevention

Primary Prevention

Rx - Statin therapyPl –PlaceboPra –pravastatinAtv - atorvastatin

200(5.2)

PROVE-IT -Pra

PROVE-IT –Atv

TNT –Atv10

TNT –Atv80

Design of Key Statin Trials (2)Design of Key Statin Trials (2)Design of Key Statin Trials (2)

atorva

10 mg od

Low/average3.4(130)

10,305 40-79 yrs

>3 risk factors

ALLHAT-LLT9prava

40 mg od

HypertensionSome CVD

10,355 >55 yrs

Average3.8(146)

4.8

StatinCVD/risk factors

Patientsage

Mean LDL-C mmol/L (mg/dL)

Follow-up (years)Study

CARDS10atorva

10 mg od

Diabetes + 1 other risk factor

2838 40-75 yrs

Low/average3.0(115)

4.0

3.3 ASCOT-LLA8

PROVE-IT11atorva 80 mg

prava 40 mg

od

Yes 4162>18 yrs

Low/average2.7(106)

3.0

TNT12 Yes 10,001 35-75 yrs

Low/average 2.5(98)

4.9atorva 10 mg

atorva 80 mg

od

1. 4S Study Group. Lancet 1994;344:1383–1389. 2. Shepherd J et al. N Engl J Med1995;333:1301–1307. 3. Sacks FM et al. N Engl J Med.

IDEAL13 Yes

MI

8888<80 yrs

Low/average 3.1(121)

4.8atorva 80 mg

simva 20 mg

od

Design of Key Statin Trials (1)Design of Key Statin Trials (1)Design of Key Statin Trials (1)

4S1

WOSCOPS2

CARE3

LIPID4

AFCAPS/

TexCAPS5

simva

20 mg od

prava

40 mg od

prava

40 mg od

prava

40 mg od

lova

40 mg od

Yes

No MI,

angina

(5% )

Yes

Yes

Low HDL-C

No CHD

5.4

4.9

5.0

6.1

5.2

4444

35–70 yrs

6595

male only

45–64 yrs

4159

21–75 yrs

9014

31–75 yrs

6605

45–73 yrs

Raised 4.9(188)

Raised 5.0(192)

Low/average 3.6(139)

Average 3.8(147)

Average 3.9(150)

StatinCVD/risk factors

Patientsage

Mean LDL-C mmol/L (mg/dL)

Follow-up (years)Study

HPS6Yessimva

40 mg od

20,536 40-80 yrs

Low/average 3.4(130)

5.0

5804 prava 3.2Average

Yes

SummarySummarySummary

�Atherosclerosis is associated with CVD, which is a major cause of death in developed countries

�Dyslipidaemia, in particular elevated LDL-C and low HDL-C, is associated with increased risk for CVD

�Large statin trials have shown that the lower the level of LDL-C achieved the greater the reduction in CV events

�Guidelines recommend lipid levels to reduce the morbidity and mortality caused by dyslipidaemia, and proposed recommendations suggest even more

Aterosclerosi, Colesterolo, Statine e Rischio Cardiovascolare

1Greco Eugenio - 2Greco Raffaella 1Departement of Internal Medicine, Institute Ninetta Rosano-Clinica Tricarico, Belvedere M.mo (CS) - 2Scientific Institute Ospedale San Raffaele, Milan - ITALY