1 / 37

CAMPAGNA EDUCAZIONALE REGIONALE ANMCO TOSCANA “Difendiamo il Cuore” Casciana Terme 12 Gennaio 2008

CAMPAGNA EDUCAZIONALE REGIONALE ANMCO TOSCANA “Difendiamo il Cuore” Casciana Terme 12 Gennaio 2008 Dai grandi Trials con Statine al razionale del target terapeutico del Colesterolo in Prevenzione Secondaria Dr. Stefano Viani UO Malattie Cardiovascolari Ospedale di Pontedera USL 5 Pisa.

ursula
Download Presentation

CAMPAGNA EDUCAZIONALE REGIONALE ANMCO TOSCANA “Difendiamo il Cuore” Casciana Terme 12 Gennaio 2008

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. CAMPAGNA EDUCAZIONALE REGIONALE ANMCO TOSCANA “Difendiamo il Cuore” Casciana Terme 12 Gennaio 2008 Dai grandi Trials con Statine al razionale del target terapeutico del Colesterolo in Prevenzione Secondaria Dr. Stefano Viani UO Malattie Cardiovascolari Ospedale di Pontedera USL 5 Pisa

  2. La mortalità regionale per IHD tra il 1990 e il 2020 Mortalità per IHD (migliaia) La mortalità per malattia ischemica del cuore (IHD) è alta e aumenterà EME=mercati con economie stabili; FSE=economia ex socialiste; OAI=altri paesi asiatici e isole del Pacifico; SSA=Africa sub-sahariana; LA=America Latina; Mid East=Medio Oriente. Yusuf S et al. Circulation. 2001;104:2746-2753.

  3. Studio INTERHEART(15.152 casi e 14.820 controlli)Lancet 3 settembre 2004 Nove fattori di rischio, facilmente misurabili, “spiegano” oltre il 90% degli infarti in tutte le regioni del mondo” • Fumo • Ipertensione • Diabete • Dislipidemia • Obesità addominale • Stress • Inattività fisica • Scarsa assunzione di frutta e verdura • Nulla assunzione di alcool L’associazione di più fattori di rischio moltiplica la probabilità di infarto: … … chi presenta tutti i nove fattori ha una probabilità di infarto che è più di 330 volte superiore a quella di chi non ne ha nessuno (90% probabilità) !!!!!!

  4. RISCHIO CARDIOVASCOLARE E COLESTEROLEMIA

  5. EFFETTI NON IPOLIPEMIZZANTI (effetto precoce/rapido) EFFETTI IPOLIPEMIZZANTI (effetto lento/ritardato) Disfunzione/attivazione endoteliale Statine Fegato Sintesi colesterolo epatico Infiammazione/ attivazione immunologica Coagulazione/ attivazione piastrine inibitorio Statine inibitorio inibitorio inibitorio Rottura della placca/ occlusione trombotica trombo Nucleo lipidico Placca aterosclerotica ricca di lipidi Adapted from Ray KK et al. J Am Coll Cardiol. 2005;46:1425-1433. Effetti delle Statine Inibizione HMG-CoA reduttasi

  6. Trials di Prevenzione Secondaria con Statine NCEP-ATP III 2001 4 S 1994 CARE 1996 LIPID 1998 HPS 2002 TNT 2005 IDEAL 2005 UPDATE 2004 • Popolazione ad“Alto Profilo di Rischio” • Definizione del target LDL-C • Alte dosi vs basse dosi • Coronaropatia • Elevati valori di LDL-C • Valori di LDL-C nella media

  7. 4S Scandinavian Simvastatin Survival Study • 4444 pts • Pregresso Infarto del Miocardio/ • Angina Stabile • Colesterolo totale medio 272+23 mg/dl • (in terapia dietetica) • Simvastatina 20 mg/die (40 mg/die 37%) • vs Placebo • Riduzione LDL-C 38% nel gruppo trattato • Follow-up: 5.6 anni • -30% mortalità totale • -34% mortalità per CHD Lancet 1994

  8. CARE Cholesterol and Recurrent Events Trial • 4159 pts (M 86%) • Pregresso Infarto del Miocardio • (media 10 mesi dalla randomizzazione) • Colesterolo totale < 240 mg/dl • (in terapia dietetica) • Colesterolo LDL tra 115 e 174 mg/dl • (media 139 mg/dl) • Pravastatina 40 mg/die vs Placebo • Follow-up: 5 anni • End point I: evento coronarico fatale o • infarto miocardico non fatale Mean LDL-C level reduced by 32% 97 to 98 mg/dl throughout the 5 yr FU Sacks FM et al. NEJM 1996

  9. LIPID The Long-term Intervention with Pravastatin in Ischaemic Disease Study • 9014 pts (M 83%) • Pregresso Infarto del Miocardio • /Pregressa Angina Instabile (64%/36%) • Colesterolo totale medio 218 mg/dl • (in terapia dietetica) • Colesterolo LDL tra 130 e 170 mg/dl • (media 150 mg/dl) • Pravastatina 40 mg/die vs Placebo • Follow-up: 6.1 anni • End point I: mortalità per evento • coronarico Lipid Study Group. NEJM 1998

  10. NCEP-ATP III Risk Categories (www.cuore.iss.it/valutazione/carte.asp) High Risk CHD, PVD, Diabetes 2 + RF (10 yr risk > 20%) LDL-C goal < 100 mg/dl Moderate Risk 2 + RF (10 yr risk > 10%) LDL-C goal < 130 mg/dl Lower Risk 0-1 RF (10 yr risk > 20%) LDL-C goal < 160 mg/dl Moderately High Risk 2 + RF (10 yr risk 10-20%) LDL-C goal < 130 mg/dl JAMA 2001

  11. NCEP-ATP III Treatment Algorithm In High Risk Patients 2001 LDL-C > 130 Therapeutic Indication TLC and Statin LDL-C 100-129 TLC/Statin/ Fibrates/ Nicotinic Acid Therapeutic Options LDL C < 100 No Lowering Therapy LDL-C Goal JAMA 2001

  12. Possible Relationship between LDL-C and CHD Risk (2001) Threshold: unnecessary to go very low CHD Risk Curvilinear: the lower the better with diminishing returns Linear: the lower the better LDL-C mg/dl 60 100

  13. HPS Study (Heart Protection Study Investigators) • 20536 UK pts (40-80 yr) • High Risk pts CHD, PVD, Diabetes • Variable LDL-C at baseline (TLC) • Simvastatin 40 mg/die vs Placebo (also vitamins arm) • Follow-up: 5 yr • Results • 13% reduction all cause death • 24% reduction major vascular events • 27% reduction major coronary events • 25% reduction stroke • 24% reduction revascularization Lancet 2002

  14. HPS: Reduction of Major Cardiovascular Events according to baseline LDL-C (mg/dl) P<0.00001 Lancet 2002

  15. HPS Study: CVD Risk reduction according to LDL-C level “The lower the better” Log CVD Risk 26% reduction CVD 22% reduction CVD LDL-C mg/dl 60 100 Lancet 2002

  16. NCEP ATP III: LDL-C Goals(2004 proposed modifications) Moderately High Risk High Risk CHD or CHD risk equivalents ACS Moderate Risk Lower Risk 190 - Target <160 mg/dL 160 - *In high-risk patients with high TG (>200 mg/dl) or low HDL-C consider fibrates/nicotinic acid LDL-C level Target <130 mg/dL 130 - Target <130 mg/dL Target <100 mg/dL 100 - Optional goal <100 mg/dL Optional goal <70 mg/dL* 70 - Grundy SM et al. Circulation 2004

  17. Considerations and Limitations for achieving very low LDL-C levels • Dangers from very low LDL-C (unlikely) • High baseline LDL-C levels (> 150 mg/dl, max drug lowering about 50%) • Side effects of high drug doses

  18. TNT Study (Treating to New Targets Investigators) • 10001 pts (M 81%) • Clinically evident, stable CHD (58.5% previous myocardial infarction) • LDL-C < 130 mg/dl (mean 98+18/97+18 mg/dl, • after a 8 w open-label treatment with Atorva 10 mg/die) • Atorvastatin 10 mg/die vs Atorvastatin 80 mg/die • Follow-up: 4.9 yrs • End point I: occurrence of a first major CV event (death from CHD • non fatal myocardial infarction, resuscitation after cardiac arrest, fatal • or nonfatal stroke) La Rosa JC et al. NEJM 2005

  19. IDEAL Study (Incremental Decrease in End Points Through Aggressive Lipid Lowering) • 8888 pts (M 81%) • Previous Myocardial Infarction • LDL-C < 130 mg/dl (mean 121.4+0.5/121.6+0.5 mg/dl) • Simvastatin 20 mg/die vs Atorvastatin 80 mg/die • Follow-up: 4.8 yrs • End point I: occurrence of a first major CV event (death from CHD • non fatal myocardial infarction, resuscitation after cardiac arrest) Pedersen TR et al. JAMA 2005

  20. …intensive lowering of LDL-C did not result in a significant reduction of the primary outcome of major coronary events, but did reduce the risk of other secondary end points and nonfatal acute MI. Pts with MI may benefit from intensive lowering of LDL-C without an increase in non-CV mortality or other serious adverse reaction

  21. TNT IDEAL A10 A80SA80 Adverse Events resulting in 5.8 8.1 p<.001 4.2 9.6 p<.001 permanent discontinuation of study drug (%) ALT > 3 ULN on 2 consecutive 0.2 1.2 p<.001 0.11 0.97 p<.001 measurements (%) Myalgia (%) 4.7 4.8 p: NS 1.1 2.2 p<.001 Rhabdomyolysis (%) 0.06 0.04 p: NS 0.07 0.05 p: NS

  22. Low-density lipoprotein cholesterol (LDL-C) levels of trials comparing high-dose to standard-dose statin therapy Cannon C. P. et al. J Am Coll Cardiol 2006

  23. Individual trials and pooled analysis showing a highly significant 16% reduction in the risk of coronary death or any cardiovascular event (myocardial infarction, stroke, hospitalization for unstable angina, or revascularization) (p < 0.0001) Cannon C. P. et al. J Am Coll Cardiol 2006

  24. Individual trials and pooled analysis showing a highly significant 16% reduction in the risk of coronary death or myocardial infarction (p < 0.0001) Cannon C. P. et al. J Am Coll Cardiol 2006

  25. Individual and pooled analyses showing: A) non-significant trend in reduction of cardiovascular death B) no increased risk of non-cardiovascular mortality C) a non-significant trend toward decreased overall mortality with high-dose statins Cannon C. P. et al. J Am Coll Cardiol 2006

  26. Stroke Risk reduction in High Risk Patients Statin standard dose vs Placebo High dose vs Standard dose

  27. Prevenzione con Statine nei Soggetti ad Alto Rischio (= Prevenzione Secondaria) • Le modificazioni “terapeutiche” dello stile di vita sono una componente essenziale • del trattamento di questi pazienti • La riduzione del LDL-C determina un significativo beneficio in termini di mortalità • e morbilità cardiovascolare • Tanto più si riducono i valori di LDL-C tanto maggiore è il beneficio in termini di • riduzione del rischio (the lower the better). In particolare la terapia con statine è • ragionevole anche in soggetti ad alto rischio con LDL-C < 100 mg/dl con un target • terapeutico < 70 mg/dl • La terapia con alte dosi conferisce un significativo vantaggio se confrontata con • quella a dosi standard particolarmente nella prevenzione degli eventi cardiovascolari • non fatali (ogni milione di pts trattati con alte dosi si eviterebbero 35000 eventi CV, • più di 14000 morti coronariche o infarto del miocardio, con un NNT di 29 per 2 aa • nei pazienti con SCA, per 5 aa nei pazienti con coronaropatia stabile)

  28. Special ArticleExplaining the Decrease in U.S. Deaths from Coronary Disease, 1980-2000 Approximately half the decline in U.S. deaths from coronary heart disease from 1980 through 2000 may be attributable to reductions in major risk factors and approximately half to evidence-based medical therapies Remember……. Guidelines that are not followed are of no value ! Ford ES et al. NEJM 2007;356:2388-2398

  29. Updated ATP III LDL-C Goals and Cutpoints for Therapy LDL-C mg/dl Risk Category Goal Initiation level Consideration level for for TLC drug therapy High Risk <100 > 100 > 100 (optional < 70)(optional < 100) Moderately High Risk <130 > 130 > 130 (optional < 100)(optional 100-129) Moderate Risk < 130 > 130 > 160 Low Risk < 160 > 160 > 190 (optional 160-189) Grundy SM et al. Circulation 2004

More Related