I nuovi obiettivi

terapeutici allo studio

con statine.

“Difendiamo il cuore”ANMCO – Toscana

9 febbraio 2008Hotel Le Dune

Lido di Camaiore

A. Del Carlo

05 ottobre 2004 - BMJ 2004; 329: 645

Statine: troppe o troppo poche

Rapporto OsMed 2006

Costo territoriale per farmaci più elevato:

Atorvastatina: da 19,4 a 21,9 DDD

Simvastatina stabile su 17 DDD

Rosuvastatina da 4,6 a 7,1 DDD

Pravastatina da 5,9 a 5,7 DDD

Nuove indicazioni allo studioper le signore inibitrici del

3-idrossi-3-metiglutaril Coenzima A reduttasi

1.Nuovi dosaggi (alti!)

2.Nuove indicazioni (oltre CHD)

3.Nuove suggestioni

TRIALS con STATINEAcute coronary event

MIRACL, PROVE IT

4S, HPS, TNT

AFCAPS/TexCAPS,WOSCOPS, ASCOT, CARDS

CARE1, LIPID2, SEARCH, IDEAL

4 moNo history of CAD Unstable CAD

Randomization:24–96 h

3 mo

t=0

6 moRandomization:CARE - 3–20 moLIPID - 3–36 mo

Randomization:>6 mo

Stable CAD

Primary prevention Secondary prevention

Schwartz GG et al. Am J Cardiol 1998;81:578–581.Duration of follow-up: 15.0 years; 26.1 years; 35.4 years.

Coo

yrig

ht 2

000

– 20

04 Q

UB

Isof

t

Figure 1. Median Low-Density Lipoprotein (LDL) Cholesterol Levels during the Study.

PROVE IT – TIMI 22

Figure 2. Kaplan–Meier Estimates of the Incidence of the Primary End Point of Death from Any Cause or a Major Cardiovascular Event. Intensive lipid lowering with the 80-mg dose of atorvastatin, as compared with moderate lipid lowering with the 40-mg dose of pravastatin, reduced the hazard ratio for death or a major cardiovascular event

by 16 percent.

PROVE IT – TIMI 22

Figure 3. Hazard Ratio for the the Primary End Point of Death from Any Cause or a Major Cardiovascular Event at 30, 90, and 180 Days and at the End of Follow-up in the High-Dose Atorvastatin Group, as Compared with the Standard-Dose Pravastatin Group. Event rates are Kaplan–Meier estimates censored at the time points indicated with the use of the average duration of follow-up (two years). CI denotes confidence interval.

PROVE IT – TIMI 22

Figure 4. Estimates of the Hazard Ratio for the Secondary End Points and the Individual Components of the Primary End Point in the High-Dose Atorvastatin Group, as Compared with the Standard-Dose Pravastatin Group. CI denotes confidence interval, CHD coronary heart disease, and MI myocardial infarction. Revascularization was performed at least 30 days after randomization.

Ideal studyPrev. sec. Atorva 80 vs Simva 20 o 40

Table 1. Lipid Levels During Treatment

 Atorvastatin mg/dL (mmol/L)

Simvastatin mg/dL (mmol/L)

LDL-cholesterol 81 (2.1) 104 (2.7)

HDL-cholesterol 47 (1.22) 46 (1.19)

HDL = high-density lipoprotein; LDL = low-density lipoprotein

Ideal study

Table 2. Primary Composite Endpoint

  Simvastatin (%) Atorvastatin (%) HR 95% CI P Value

Major coronary event 10.4 9.3 0.89 0.78-1.01 .07

CHD death 4.0 3.9 0.99 0.80-1.22 .90

Nonfatal MI 7.2 6.0 0.83 0.71-0.98) .02

Cardiac arrest with resuscitation 0.2 0.2      

CHD = coronary heart disease; CI = confidence interval; HR = hazard ratio; MI = myocardial infarction

MIRACL: study design

Hospitalizationfor

unstable anginaor non-Q MI

n=3086Randomized

24–96 hoursafter admission

Placebo + diet

Atorvastatin 80 mg + diet

16 weeks

Assessments conducted at weeks 0, 2, 6 and 16

Schwartz GG et al. Am J Cardiol 1998;81:578–581.

MIRACL: plasma LDL-C valuesat baseline, 6 and 16 weeks

*p<0.0001 vs placebo at 6 and 16 weeks.Schwartz GG et al. Jama 2001; 285: 1711-1718

0

60

120

180

240

Baseline 6 Weeks End of study

LD

L-C

(m

g/d

L)

* *

Atorvastatin 80 (- 40%)

Placebo

Coo

yrig

ht 2

000

– 20

04 Q

UB

Isof

t

MIRACL: primary efficacy measure

Relative risk = 0.84p=0.048

Atorvastatin

Placebo

0

5

10

15

0 4 8 12 16Time since randomization (weeks)

Cu

mu

lati

ve I

nci

den

ce (

%)

Time to first occurrence of:• Death (any cause)• Nonfatal MI• Resuscitated cardiac arrest• Worsening angina with new

objective evidence requiring urgent rehospitalization

17.4%

14.8%

Schwartz GG et al. Jama 2001; 285: 1711-1718

Coo

yrig

ht 2

000

– 20

04 Q

UB

Isof

t

MIRACL: worsening angina with new objective evidence of ischemia requiring urgent rehospitalization

0

3

6

9

0 4 8 12 16Time since randomization (weeks)

Cu

mu

lati

ve In

cid

enc

e (%

)

Relative risk = 0.74p=0.02

Atorvastatin

Placebo 8.4%

6.2%

Schwartz GG et al. Jama 2001; 285: 1711-1718

MIRACL: fatal or nonfatal stroke

0

0.5

1

1.5

2

0 4 8 12 16

Time since randomization (weeks)

Cu

mu

lati

ve I

nci

den

ce (

%)

Relative risk = 0.50p=0.045

Atorvastatin

Placebo 1.6%

0.8%

Schwartz GG et al. Jama 2001; 285: 1711-1718

Is lower better?

SAGE Trial: Background

• The purpose of the SAGE study was to compare the effects of intensive versus moderate statin therapy on the reduction of myocardial ischemia, as assessed by ambulatory ECG, in older men and women with stable CAD.

• The purpose of the SAGE study was to compare the effects of intensive versus moderate statin therapy on the reduction of myocardial ischemia, as assessed by ambulatory ECG, in older men and women with stable CAD.

Deedwania et al. Circulation. 2007 Feb 13; 115: 700 - 707.Deedwania et al. Circulation. 2007 Feb 13; 115: 700 - 707.

SAGE Trial: Study Design

Primary Efficacy Parameter: Absolute change from baseline in Primary Efficacy Parameter: Absolute change from baseline in total duration of total duration of myocardial ischemiamyocardial ischemia on 48-hour Holter Monitor on 48-hour Holter Monitor

Secondary Efficacy Parameters: (1) absolute change in total duration of Secondary Efficacy Parameters: (1) absolute change in total duration of ischemia from baseline to month 3; from baseline to month 3 and to month 12: ischemia from baseline to month 3; from baseline to month 3 and to month 12: (2) the % change in total duration of ischemia, (3) the absolute and % change in (2) the % change in total duration of ischemia, (3) the absolute and % change in no. of ischemic episodes, (4) the % change in ischemic burden, (5) the no. of ischemic episodes, (4) the % change in ischemic burden, (5) the proportion of patients who were totally free of ischemia, and (6) the % change in proportion of patients who were totally free of ischemia, and (6) the % change in the levels of total cholesterol, LDL-C, high-density lipoprotein cholesterol (HDL-the levels of total cholesterol, LDL-C, high-density lipoprotein cholesterol (HDL-C), triglycerides, and apolipoprotein B.C), triglycerides, and apolipoprotein B.

Primary Efficacy Parameter: Absolute change from baseline in Primary Efficacy Parameter: Absolute change from baseline in total duration of total duration of myocardial ischemiamyocardial ischemia on 48-hour Holter Monitor on 48-hour Holter Monitor

Secondary Efficacy Parameters: (1) absolute change in total duration of Secondary Efficacy Parameters: (1) absolute change in total duration of ischemia from baseline to month 3; from baseline to month 3 and to month 12: ischemia from baseline to month 3; from baseline to month 3 and to month 12: (2) the % change in total duration of ischemia, (3) the absolute and % change in (2) the % change in total duration of ischemia, (3) the absolute and % change in no. of ischemic episodes, (4) the % change in ischemic burden, (5) the no. of ischemic episodes, (4) the % change in ischemic burden, (5) the proportion of patients who were totally free of ischemia, and (6) the % change in proportion of patients who were totally free of ischemia, and (6) the % change in the levels of total cholesterol, LDL-C, high-density lipoprotein cholesterol (HDL-the levels of total cholesterol, LDL-C, high-density lipoprotein cholesterol (HDL-C), triglycerides, and apolipoprotein B.C), triglycerides, and apolipoprotein B.

Atorvastatin80 mg/dn=377

Atorvastatin80 mg/dn=377

Pravastatin40 mg/dn=374

Pravastatin40 mg/dn=374

893 ambulatory CAD patients 65-85 years with ≥ 1 MI that lasted ≥ 3 minutes during 48-hour ambulatory ECG at screening

Prospective. Randomized. Double-blind. Double-dummy. Multi-Center. International. Mean follow-up 12 months

893 ambulatory CAD patients 65-85 years with ≥ 1 MI that lasted ≥ 3 minutes during 48-hour ambulatory ECG at screening

Prospective. Randomized. Double-blind. Double-dummy. Multi-Center. International. Mean follow-up 12 months

RR

3 and 12 mos. follow-up3 and 12 mos. follow-up

Deedwania et al. Circulation. 2007 Feb 13; 115: 700 - 707.Deedwania et al. Circulation. 2007 Feb 13; 115: 700 - 707.

SAGE Trial: Primary Efficacy EndpointSAGE Trial: Primary Efficacy Endpoint

113.5

81.470.8

0

20

40

60

80

100

120

140

113.5

81.470.8

0

20

40

60

80

100

120

140

Atorvastatin

(n=408)

Atorvastatin

(n=408)

124.3

75.3 78.7

0

20

40

60

80

100

120

140124.3

75.3 78.7

0

20

40

60

80

100

120

140

Pravastatin

(n=396)

Pravastatin

(n=396)

BaselineBaseline Month 3Month 3 Month 12Month 12

• The total duration of myocardial ischemia at month 12 was significantly reduced from baseline in both atorvastatin- and pravastatin-treated patients.

• There was no significant difference between atorvastatin and pravastatin.

To

tal

du

rati

on

of

Myo

card

ial

Isch

emia

(m

in)

To

tal

du

rati

on

of

Myo

card

ial

Isch

emia

(m

in)

Mean total duration of myocardial ischemia over 48 hours

P<0.001P<0.001 P<0.001P<0.001

Deedwania et al. Circulation. 2007 Feb 13; 115: 700 - 707.Deedwania et al. Circulation. 2007 Feb 13; 115: 700 - 707.

-40,9

-56,3

-32,1

2,25,8

-39,6

-21,3

-55,4

-32,4

5,57,6

-21,9

-60

-50

-40

-30

-20

-10

0

10

20

-40,9

-56,3

-32,1

2,25,8

-39,6

-21,3

-55,4

-32,4

5,57,6

-21,9

-60

-50

-40

-30

-20

-10

0

10

20

SAGE Trial: Lipid ParametersSAGE Trial: Lipid Parameters

TotalTotal LDLLDL HDLHDL

Least Squares Mean Percent Changes in Lipid Parameters from Baseline

p=0.009p=0.009

p<0.001p<0.001

p<0.001p<0.001

AtorvastatinAtorvastatin AtorvastatinAtorvastatin

AtorvastatinAtorvastatin

PravastatinPravastatin PravastatinPravastatin

PravastatinPravastatin

Month 3Month 3

Month 12Month 12

Deedwania et al. Circulation. 2007 Feb 13; 115: 700 - 707.Deedwania et al. Circulation. 2007 Feb 13; 115: 700 - 707.

LS

mea

n p

erce

nt

chan

ge

LS

mea

n p

erce

nt

chan

ge

Statine e stroke

Efficacia delle statine nella prevenzione dell’ictus

Zhou et al. Am H J. 2006; 151:273-81.

Studi su simvastatina4S 0,74 (0,52 – 1,94)HPS 0,76 (0,67 – 0,86)Unificati (IC 95%) 0,76 (0,69 – 0,85)Studi su pravastatinaCARE 0,60 (0,40 – 0,57)LIPID 0,03 (0,60 – 1,61)PROSPER 1,04 (0,02 – 1,31)WOSCOPS 0,90 (0,61 – 1,34) Unificati (IC 95%) 0,87 (0,76 – 1,02)Con ALLHAT-LLTALLHAT-LLT 0,91 (0,76 – 1,09)CARE 0,60 (0,40 – 0,97)LIPID 0,01 (0,60 – 1,01)PROSPER 1,04 (0,02 – 1,31)WOSCOPS 0,90 (0,61 – 1,34) Unificati (IC 95%) 0,66 (0,73 – 0,55) Studi su atorvastatinaASCOT-LLA 0,75 (0,56 – 0,95)CARDS 0,53 (0,51 – 0,90) Unificati (IC 95%) 0,68 (0,55 – 0,88)Con GREACEASCOT-ILA 0,73 (0,56 – 0,96)CARDS 0,53 (0,31 – 0,90)GREACE 0,53 (0,34 – 1,16)Unificati (IC 95%) 0,68 (0,59 – 0,06)

0,2 0,5 1,0 2,0 5,0

RR e IC 95% sulla base di un modello per effetti randomEventi cerebrovascolari maggiori(ictus fatali e non fatali)

A favore del controllo A favore della statina

RR

0,76

0,87

0,68

0,88

0,68

0

1

2

3

4

5

6

Simvastatina 40mg Placebo

Rid

uzi

on

e %

Del

ris

chio

di

ictu

s

(n=444)(n=444) (n=585)(n=585)

4.34.3

5.75.7

-25%-25%(p=0,0001)(p=0,0001)

Heart Protection Study con simvastatina 40mgRiduzione del rischio di ictus

TUTTI I PAZIENTITUTTI I PAZIENTI

CARDS: atorvastatina 10 e ictus in pazienti diabetici senza CHD

Modificato da Colhoun HM et al. Lancet. 2004; 364:685-696; Newman C et al. Accettato per presentazione all’American Heart Association Scientific Sessions 2005; Dallas, TX. 13-16 novembre 2005.

Endpoint primario 127 (9,0) 83 (5,8) –37% (–52, –17)

Eventi coronarici acuti 77 (5,5) 51 (3,6) –36% (–55, –9)

Rivascolarizzazione coronarica 34 (2,4) 24 (1,7) –1% (–59, +16)

Ictus 39 (2,8) 21 (1,5) –48% (–69, –11)

* Numero di pazienti con evento (%).

0,4 0,6 0,8 1,0 1,2

Evento Placebo* Atorva* Rapporto di rischio Rischio relativo (IC)

A favore placeboA favore atorvastatina

0,2

(n=2.841)

p=0,001

PROSPER Study Group

Obiettivo dello studioObiettivo dello studio

PROSPER Study Group

Obiettivo dello studioObiettivo dello studio Determinare se pravastatina al dosaggio di 40

mg/die riduca gli eventi cardio e cerebro

vascolari (morte, IMA, ictus) nei pazienti anziani

ad alto rischio o affetti da patologia vascolare.

Follow up medio 3,2 a.

Determinare se pravastatina al dosaggio di 40

mg/die riduca gli eventi cardio e cerebro

vascolari (morte, IMA, ictus) nei pazienti anziani

ad alto rischio o affetti da patologia vascolare.

Follow up medio 3,2 a.

PROSPER Study Group. Lancet. 2002PROSPER Study Group. Lancet. 2002

• 5804 pazienti (70–82 anni) ad alto rischio

• Terapia: pravastatina 40 mg vs. placebo

• 19% di riduzione di eventi coronarici maggiori

• 24% riduzione di mortalità cardiovascolare

• 25% riduzione in TIA (non stroke riduzione)

Shepherd J et al. Lancet 2002;360:1623–1630.

Risultati

Statine e ictus cerebrale

* p<0,001

Le statine riducono apparentemente tutti gli ictus del 20%, ma tale riduzione è dovuta a una riduzione del 28% dell’ictus tromboembolico. Ciò spiega perché la riduzione degli ictus per effetto delle statine sia stata osservata soprattutto negli studi condotti in pazienti con pregresse malattie cardiovascolari, nei quali è più frequente l’ictus ischemico.

Trials randomizzati

Categoria No. trials No. eventiVariazione %

del rischio (IC 95%)

Tutti gli ictus 41 3.319 -20* (-14/-26)

Tutti gli ictus nei pazienti con pregresse malattie cardiovascolari 32 2.311 -22* (-28/-16)

Tutti gli ictus nei pazienti senza pregresse malattie cardiovascolari 7 752 -6 (-22/14)

Ictus tromboembolico 8 1.204 -28* (-35/-20)

Ictus emorragico 8 149 -3 (-35/47)

Ictus fatale 56 678 -2 (-17/16)

Ictus non fatale 40 2.519 -23* (-29/-16)

Law MR et al. Br Med J. 2003; 326:1423-9.

La terapia con statine non è associata ad aumento del rischio di ictus emorragico

* Simvastatina vs placebo. † Atorvastatina vs cure abituali. ‡ Atorvastatina vs placebo. § Pravastatina vs trattamento convenzionale. II Pravastatina vs placebo. ¶ Lovastatina vs placebo.

Amarenco P et al. Stroke. 2004; 35:2902-2909; Yano K et al. Stroke. 1989; 20:1460-1465;Iso H et al. N Engl J Med. 1989; 320:904-910.

HPS*

GREACE†

MIRACL‡

KLIS§

LIPIDıı

CAREıı

SSSS*

AFCAPS¶

Complessivo (IC 95%)Eterogeneità

Trial

0,05 0,2 0,5 1,0 10,0

Odds ratio (IC 95%)

A favore del controllo A favore della statina

3,0

0,90 (0,65–1,22)p=0,15

Randomly assigned 4,731 patients who had had a stroke or TIA within 1 to 6 months before the study entry, had low LDL levels (100-190 mg/dL) and had no knonw CHD

2,365 atorvastatin 80 mg 2,366 placebo

Median follow-up time: 4.9 yearsSPARCL investigators, N Engl J Med 2006

3 50

Years

Fata

l or n

on-fa

tal s

trok

e (%

)

8

12

16

20

4

0

Placebo (n=2,366)

Atorvastatin (n=2,365)

HR 0.84 (0.71-0.99) p<0.0001

Kaplan-Meier for Kaplan-Meier for fatal or non-fatal strokefatal or non-fatal stroke in the in the SPARCL study (n=4,731); follow-up 4.9 yearsSPARCL study (n=4,731); follow-up 4.9 years

SPARCL investigators, N Engl J Med 2006

3 50

Years

Stro

ke o

r TIA

eve

nt (%

)

10

15

20

25

5

0

Placebo (n=2,366)

Atorvastatin (n=2,365)

HR 0.77 (0.67-0.88) p<0.0001

Kaplan-Meier for Kaplan-Meier for stroke or TIAstroke or TIA in the SPARCL study in the SPARCL study (n=4,731); follow-up 4.9 years(n=4,731); follow-up 4.9 years

SPARCL investigators, N Engl J Med 2006

SPARCL: Main results

Welch M et al. 15th European Stroke Conference; May 16-19, 2006; Brussels, Belgium.

Type of stroke Hazard ratio with atorvastatin

Any 0.84

Fatal 0.57

Nonfatal 0.87

Ischemic 0.78HemorrhagicNessuna riduzione della morte globale

1.66

SPARCL

L’Incremento di stroke emorragico è dovuto all’effetto pleiotropico antiaggregante?

I dati in letteratura sono ancora controversi (HPS +; Prosper -)

Il Pharmacovigilance Working Party dell’EMEA probabilmente inserirà una modifica sul riassunto delle caratteristiche del prodotto.

Statine e scompenso cardiaco

Small prospective clinical studies of atorvastatin and simvastatin in systolic HF are promising, documenting improved ventricular systolic function and decreased inflammatory biomarkers with statin therapy.

Expert Opin Pharmacother. 2007 Dec;8(17):3061-8. LinksAtorvastatin and statins in the treatment of heart failure.Horwich TB, MacLellan WR.

Rosuvastatina e rimodellamento ventricolare

Despite being safe and effective at decreasing plasma cholesterol, high-dose ROS did not beneficially alter parameters of LV remodeling.

J Card Fail. 2007 Feb;13(1):1-7. Double-blind, randomized, placebo-controlled study of high-dose HMG CoA reductase inhibitor therapy on ventricular remodeling, pro-inflammatory cytokines and neurohormonal parameters in patients with chronic systolic heart failure.Krum H, Ashton E, Reid C, Kalff V, Rogers J, Amarena J, Singh B, Tonkin A.

Studio CORONARosu 10 vs plb – paz. > 60 aa

scompenso ischemico

Rosuvastatin did not reduce the primary outcome or the number of deaths from any cause in older patients with systolic heart failure, although the drug did reduce the number of cardiovascular hospitalizations.

N Engl J Med. 2007 Nov 29;357(22):2301-4. Rosuvastatin in older patients with systolic heart failure.Kjekshus J, Apetrei E, Barrios V, Böhm M, Cleland JG, Cornel JH, Dunselman P, Fonseca C, Goudev A, Grande P, Gullestad L, Hjalmarson A, Hradec J, Jánosi A, Kamenský G, Komajda M, Korewicki J, Kuusi T, Mach F, Mareev V, McMurray JJ, Ranjith N, Schaufelberger M, Vanhaecke J, van Veldhuisen DJ, Waagstein F, Wedel H, Wikstrand J; CORONA Group.

Rimaniamo in attesa ….

…dei risultati del GISSI – HF

Paz. con diagnosi di SC randomizzati a n3 PUFA, Rosuvastatina e Placebo. Follow up di 3 aa.

Statine e glaucoma

Arch Ophthalmol. 2004 Jun;122(6):822-6. LinksStatins and other cholesterol-lowering medications and the presence of glaucoma.McGwin G Jr, McNeal S, Owsley C, Girkin C, Epstein D, Lee PP.

Studio caso-controllo:Sia l’uso di Statine che altri ipolipemizzanti indicherebbero la riduzione del rischio di glaucoma ad angolo aperto.

Statine e maculopatia

Br J Ophthalmol. 2003 Sep;87(9):1121-5. Links

The association between statin use and age related maculopathy.McGwin G Jr, Owsley C, Curcio CA, Crain RJ.

Studio caso – controllo

Possibile correlazione tra uso di statine e maculopatia.

Statine e rischio di frattura

Calcif Tissue Int. 2006 Jul;79(1):27-36. Epub 2006 Jul 24. Links

Statin but not non-statin lipid-lowering drugs decrease fracture risk: a nation-wide case-control study.Rejnmark L, Vestergaard P, Mosekilde L.

La correlazione è presente per tutte le statine eccetto la Prava e le non-statine.

Statine e cancro pancreatico

Pancreas. 2007 Mar;34(2):260-5. Links

Statins reduce the risk of pancreatic cancer in humans: a case-control study of half a million veterans.Khurana V, Sheth A, Caldito G, Barkin JS.

Effetto protettivo con riduzione statistica del 67% per > 6 mesi e fino all’80% > 4 anni !!!

Statine e cancro prostatico

Am J Epidemiol. 2005 Aug 15;162(4):318-25. Epub 2005 Jul 13. LinksStatins and prostate cancer risk: a case-control study.Shannon J, Tewoderos S, Garzotto M, Beer TM, Derenick R, Palma A, Farris PE.

Correlazione favorevole in particolare per cancri aggressivi.

J Natl Cancer Inst. 2006 Dec 20;98(24):1819-25. LinksStatin drugs and risk of advanced prostate cancer.Platz EA, Leitzmann MF, Visvanathan K, Rimm EB, Stampfer MJ, Willett WC, Giovannucci E.

Studio di coorte:

correlazione favorevole solo per cancri invasivi e metastatici.

Statine e cancro colorettale

Gastroenterology. 2007 Aug;133(2):393-402. Epub 2007 May 21. LinksRisk of colorectal cancer in patients prescribed statins, nonsteroidal anti-inflammatory drugs, and cyclooxygenase-2 inhibitors: nested case-control study. Vinogradova Y, Hippisley-Cox J, Coupland C, Logan RF.

Correlazione positiva con FANS, non con statine.

J Natl Cancer Inst. 2007 Jan 3;99(1):32-40. LinksStatin use and risk of colorectal cancer.Coogan PF, Smith J, Rosenberg L.

Nessuna correlazione con statine

N Engl J Med. 2005 May 26;352(21):2184-92. LinksStatins and the risk of colorectal cancer.Poynter JN, Gruber SB, Higgins PD, Almog R, Bonner JD, Rennert HS, Low M, Greenson JK, Rennert G.

Riduzione RR 47%.

Statine e cancro mammarioJ Natl Cancer Inst. 2006 May 17;98(10):700-7. Links

Statin use and breast cancer: prospective results from the Women's Health Initiative.Cauley JA, McTiernan A, Rodabough RJ, LaCroix A, Bauer DC, Margolis KL, Paskett ED, Vitolins MZ, Furberg CD, Chlebowski RT; Women's Health Initiative Research Group.

Nessuna associazione di classe. Possibile lieve correlazione con statine idrofobiche.

Cancer Epidemiol Biomarkers Prev. 2007 Mar;16(3):416-21. LinksStatin use and breast cancer risk in a large population-based setting.Boudreau DM, Yu O, Miglioretti DL, Buist DS, Heckbert SR, Daling JR.

Nessuna associazione

Statine e cancro in generale

J Natl Cancer Inst. 2008 Jan 16;100(2):134-9. Epub 2008 Jan 8. LinksThe association between statins and cancer incidence in a veterans population.Farwell WR, Scranton RE, Lawler EV, Lew RA, Brophy MT, Fiore LD, Gaziano JM.

Rischio ridotto.

Circulation. 2007 Jan 2;115(1):27-33. Epub 2006 Dec 18. LinksStatins and the risk of lung, breast, and colorectal cancer in the elderly.Setoguchi S, Glynn RJ, Avorn J, Mogun H, Schneeweiss S.

Nessuna correlazione.

Statine e demenza

Dement Geriatr Cogn Disord. 2007;23(3):194-201. Epub 2007 Jan 25. LinksPrevention and treatment of dementia or Alzheimer's disease by statins: a meta-analysis.Zhou B, Teramukai S, Fukushima M.

Nessun beneficio su rischio di demenza.

Arch Gen Psychiatry. 2005 Feb;62(2):217-24. LinksDo statins reduce risk of incident dementia and Alzheimer disease? The Cache County Study.Zandi PP, Sparks DL, Khachaturian AS, Tschanz J, Norton M, Steinberg M, Welsh-Bohmer KA, Breitner JC; Cache County Study investigators.

Nessuna associazione

Statine e AR

Lancet. 2004 Jun 19;363(9426):2015-21. Links

Trial of Atorvastatin in Rheumatoid Arthritis (TARA): double-blind, randomised placebo-controlled trial.McCarey DW, McInnes IB, Madhok R, Hampson R, Scherbakov O, Ford I, Capell HA, Sattar N.

Piccolo trial (n=116) con breve F.U. (6 mesi).

Modesto effetto antiinfiammatorio

Statine e rischio di rabmiolisi

Pharmacoepidemiol Drug Saf. 2007 Mar;16(3):352-8. Links

Risk factors for statin-associated rhabdomyolysis.Schech S, Graham D, Staffa J, Andrade SE, La Grenade L, Burgess M, Blough D, Stergachis A, Chan KA, Platt R, Shatin D.

Studio caso controllo

Soprattutto nell’età avanzata e con fattori aggiunti come alti dosaggi, malattia renale e genere femminile.

FINE

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