Gaetano GioffrèCardiologia Ospedale S. Eugenio,                          Roma
  E’ vero che le statine hanno dimostrato  un effetto protettivo nella  rivascolarizzazione miocardica attraverso  meccan...
E’ reale l’efficacia delle statinenei pazienti sottoposti a PCI ?                               g. gioffrè
Statin Therapy After Coronary                           Artery Stent Implantation                         6               ...
Risk Ratios for Various Variables Comparing     Statins vs No Statins Therapy After Coronary                    Artery Ste...
g. gioffrè
Cumulative Incidence of Major Cardiovascular            Events in Patients with Previous PCIJohnson C et al. Am J Cardiol ...
Why Statins Are Beneficial in Patients Undergoing PCI ?                           g. gioffrè
Potential Mechanisms          for Benefit• Stent/Procedure independent effects Stabilization and regression of coronary AT...
Am J Cardiol 2007; 100:170-176   g. gioffrè
Inflammatory Plaque Activation                                                     Endothelial Dysfunction                ...
Inflammatory Plaque Passivation  Unstable Plaque            Stable Plaque                    Statin                       ...
Protection From Procedural        Myocardial Injury (Early Effect)• Coronary effect (anti-thromboembolic)  - reduced dista...
Distal                                     embolization of                                     plaque debris and          ...
Platelet-Derived CD40LThe Switch-Hitting Player of Cardiovascular Disease     CRP            P André, et al Circulation. 2...
Effect of 3 Days Treatment with                               Atorvastatin                            on Platelet CD40L   ...
40 pts with carotid stenosis >40%Randomization to 10 or 80 mg AtorvastatinAssessment at baseline and 12 weeks             ...
Ultrasmall SuperParamagnetic           Transcranial Doppler DataIron-Oxide Enhanced Carotid MR             Embolization Ac...
Post-procedural 24-h percent increase from             baseline of adhesion molecule levels                               ...
Effects of 80 mg Atorvastatin on CRP After               Stenting in Patients with Stable Angina                      18  ...
Effects of 80 mg Atorvastatin on                               Cardiovascular Events After Stenting                       ...
Protection From Procedural        Myocardial Injury (Early Effect)• Coronary effect (anti-thromboembolic)  - reduced dista...
Infarction developed in the risk zone in hearts treated for one or three          days with atorvastatin or methylcellulos...
Short Lasting Pleiotropic Effects of Statins             Cholesterol              Synthesis              STATINS          ...
Adaptation to ischemia during PCI                        First Inflation                  Second Inflation                ...
Ischemic Myocardial Preconditioning and ATorvastatin          during Percutaneous Coronary Intervention                   ...
Short Lasting Pleiotropic Effects of Statins             Cholesterol              Synthesis               STATINS         ...
g. gioffrè
Periprocedural Myocardial Damage                                                           Atorvastatin                   ...
g. gioffrè
NAPLES II TRIAL                         CK-MB Increase                   Troponin I IncreaseBriguori, C. et al. J Am Coll ...
  Le statine hanno dimostrato un effetto  protettivo nella rivascolarizzazione  miocardica attraverso meccanismi  indipen...
N=502 CAD pts studied with IVUS                                       +2.7%Plaque Volume (mm3)                            ...
g. gioffrè
Primary and Secondary End PointsGibson, C. M. et al. J Am Coll Cardiol 2009;54:2290-2295              g. gioffrè
% 30                                                                     Atorvastatin                 Adjusted for LDL-C a...
•   Coronary plaque reduction/ ↓ plaque    progression•   ↑ Myocardial threshold to exercise induced-    ischemia (↑ coron...
 Start statins (asap) before PCI (possibly 1 week  before PCI). In naïve patients use a maximal  loading dose (80 mg ator...
  Le statine hanno dimostrato un effetto  protettivo nella rivascolarizzazione  miocardica attraverso meccanismi  indipen...
Si può sfruttare questa“cardioprotezione” nellachirurgia non cardiaca?                           g. gioffrè
Lipid-Lowering Angiographic Trials                    Effect on Cardiovascular Events   % 30                       (10 tri...
g. gioffrè
g. gioffrè
Incidence of Myocardial Ischemia and Troponin T Release                                             LDL-Cholesterol Reduct...
g. gioffrè
Kaplan-Meier Estimates of the Cumulative Probabilities of the Primary and      Secondary OutcomesSchouten O et al. N Engl ...
Prevenzione FA e protezionerenale                        g. gioffrè
Gaetano GioffrèCardiologia Ospedale S. Eugenio,                          Roma                gioffre.g@iol.it
Gioffrè Gaetano. Le Statine nella Chirurgia non Cardiaca. ASMaD 2012
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Gioffrè Gaetano. Le Statine nella Chirurgia non Cardiaca. ASMaD 2012

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  • Figure 1. Kaplan-Meier Estimates of the Cumulative Probabilities of the Primary and Secondary Outcomes. During the 30-day period of follow-up after surgery, perioperative myocardial ischemia (the primary outcome) occurred in 27 of the 250 patients (10.8%) in the fluvastatin group and 47 of the 247 patients (19.0%) in the placebo group (hazard ratio with fluvastatin, 0.55; 95% confidence interval [CI], 0.34 to 0.88; P=0.01). During the 30-day period of follow-up after surgery, perioperative death from cardiovascular causes or nonfatal myocardial infarction (the secondary outcome) occurred in 12 of the 250 patients (4.8%) in the fluvastatin group and 25 of the 247 patients (10.1%) in the placebo group (hazard ratio with fluvastatin, 0.47; 95% CI, 0.24 to 0.94; P=0.03).
  • Gioffrè Gaetano. Le Statine nella Chirurgia non Cardiaca. ASMaD 2012

    1. 1. Gaetano GioffrèCardiologia Ospedale S. Eugenio, Roma
    2. 2.  E’ vero che le statine hanno dimostrato un effetto protettivo nella rivascolarizzazione miocardica attraverso meccanismi dipendenti ed indipendenti dalla riduzione dei valori del colesterolo? Tale meccanismo “cardioprotettivo” può essere utile nella chirurgia non cardiaca? g. gioffrè
    3. 3. E’ reale l’efficacia delle statinenei pazienti sottoposti a PCI ? g. gioffrè
    4. 4. Statin Therapy After Coronary Artery Stent Implantation 6 Statins (3585) 5 No Statins (935) 4 Mortality (%) P<0.02 3 2 1 0 0 1 2 3 4 5 6 7 8 9 10 11 12 Months after discharge(Schomig et al., JACC 2002) g. gioffrè
    5. 5. Risk Ratios for Various Variables Comparing Statins vs No Statins Therapy After Coronary Artery Stenting Cholesterol > 200 mg% Cholesterol < 200 mg% Acute Myocardial Infarction Unstable Angina Stable Angina Diabetes No Diabetes Men Women 0 1 2 Statins Better Statins Worse(Schomig et al, JACC 2002) g. gioffrè
    6. 6. g. gioffrè
    7. 7. Cumulative Incidence of Major Cardiovascular Events in Patients with Previous PCIJohnson C et al. Am J Cardiol 2008 g. gioffrè
    8. 8. Why Statins Are Beneficial in Patients Undergoing PCI ? g. gioffrè
    9. 9. Potential Mechanisms for Benefit• Stent/Procedure independent effects Stabilization and regression of coronary ATS• Stent/Procedure dependent effects 1. Unspecific protection from procedural myocardial injury (early effect) 2. Prevention of “in-stent” restenosis (late effect) g. gioffrè
    10. 10. Am J Cardiol 2007; 100:170-176 g. gioffrè
    11. 11. Inflammatory Plaque Activation Endothelial Dysfunction (↑ vasoreactivity Platelet Deposition ↓ endothelial-dep vasodilation) (↑ platelet thrombus formation) Progenitor CellsNeoendothelization Lipid Accumulation (oxidized LDL)(↓ endothelial repair) Adventitial Neovascularization Increased Matrix Degradation (adventitial haemorrhage) (Macrophages and T cells accumulation,↑ metalloproteinases and ↓ SMC collagen synthesis) (ag/2002) g. gioffrè
    12. 12. Inflammatory Plaque Passivation Unstable Plaque Stable Plaque Statin g. gioffrè
    13. 13. Protection From Procedural Myocardial Injury (Early Effect)• Coronary effect (anti-thromboembolic) - reduced distal plaque embolization - endothelial function preservation - acute anti-inflammatory effect• Myocardial effect (Intrinsic myocardial protection) (ischemic preconditioning and anti-apoptotic effect) g. gioffrè
    14. 14. Distal embolization of plaque debris and thrombus material after PCI Debris present in 76% of filters and particles > 1000 present in 36% of filtersAngelini A et al, Circulation 2004 g. gioffrè
    15. 15. Platelet-Derived CD40LThe Switch-Hitting Player of Cardiovascular Disease CRP P André, et al Circulation. 2002;106:896. g. gioffrè
    16. 16. Effect of 3 Days Treatment with Atorvastatin on Platelet CD40L 80 Baseline After 72 hrs CD 40 L (AU) 60 40 * 20 0 Control AtorvastatinSanguigni V. et al, Circulation 2005;111:412-419. g. gioffrè
    17. 17. 40 pts with carotid stenosis >40%Randomization to 10 or 80 mg AtorvastatinAssessment at baseline and 12 weeks g. gioffrè
    18. 18. Ultrasmall SuperParamagnetic Transcranial Doppler DataIron-Oxide Enhanced Carotid MR Embolization Activity Imaging (USPIO-RMI) (1hr Monitoring) Baseline 10 mg 12 weeks 80 mg Tang, T. Y. et al. J Am Coll Cardiol g. gioffrè
    19. 19. Post-procedural 24-h percent increase from baseline of adhesion molecule levels Atorvastatin PlaceboPatti, G. et al. J Am Coll Cardiol 2006;48:1560-1566 g. gioffrè
    20. 20. Effects of 80 mg Atorvastatin on CRP After Stenting in Patients with Stable Angina 18 No statins (76) § 15 Pretreatment with statins (85) CRP levels (mg/L) Atorvastatin at stenting (62) 12 # 9 6 3 0 * Baseline 24 h 48 h After stenting g. gioffrèGaspardone A et al, Am J Cardiol 2002
    21. 21. Effects of 80 mg Atorvastatin on Cardiovascular Events After Stenting in Patients with Stable Angina 30 Combined End Points (%) Follow up: 12 months 25 20 15 P<0.05 10 5 0 No Statins Atorvastatin at Statins before Stenting StentingGaspardone A et al, Am J Cardiol 2002 g. gioffrè
    22. 22. Protection From Procedural Myocardial Injury (Early Effect)• Coronary effect (anti-thromboembolic) - reduced distal plaque embolization - endothelial function preservation - acute anti-inflammatory effect• Myocardial effect (Intrinsic myocardial protection) (ischemic preconditioning and anti-apoptotic effect) g. gioffrè
    23. 23. Infarction developed in the risk zone in hearts treated for one or three days with atorvastatin or methylcellulose (Langendorff Rats)Mensah, K. et al. J Am Coll Cardiol 2005;45:1287-1291 g. gioffrè
    24. 24. Short Lasting Pleiotropic Effects of Statins Cholesterol Synthesis STATINS Ischemic Preconditioning (ATP-K Channels)Late benefit Anti-apoptotic Effects Early benefit (PI-3,4,5) Plaque Volume/ Lipid Load Isoprenoid (GGPyP & FPyP) eNOS3 Prenilation of G-Protein Protein Kinase B (PKB/Akt) (Rho A & Ras) Inhibitory Effect Phosphatidylinositol-3 kinase (PI3K)modified fromSchulz R, J Am Coll Cardiol 2005Mensah K & Yellon D, J Am Coll Cardiol 2005Ray KK & Cannon CP, J Am Coll Cardiol 2005 g. gioffrè
    25. 25. Adaptation to ischemia during PCI First Inflation Second Inflation ST= +9 mm ST= +3 mm Pao= 105 mmHg Pao= 110 mmHg CFI= 0.04 CFI= 0.04 Pw= 10 mmHg Pw= 10 mmHgTomai F. & Gaspardone A, J Am Coll Cardiol 2002 g. gioffrè
    26. 26. Ischemic Myocardial Preconditioning and ATorvastatin during Percutaneous Coronary Intervention (IMPAT-PCI Study) Placebo 80 mg 1 hr before PCI 1st Inflation Atorvastatin 80 mg 1 hr before PCI 1st InflationGaspardone A et al, data on file g. gioffrè
    27. 27. Short Lasting Pleiotropic Effects of Statins Cholesterol Synthesis STATINS Ischemic Preconditioning (ATP-K Channels)Late benefit Anti-apoptotic Effects Early benefit (PI-3,4,5) Plaque Volume/ Lipid Load Isoprenoid (GGPyP & FPyP) eNOS3 PPARγ Prenilation of G-Protein Protein Kinase B (PKB/Akt) (Rho A & Ras) Inhibitory Effect PTEN (Phosphatase and Phosphatidylinositol-3 kinase (PI3K) tensin homolog deleted on chromosome 10) (Chronic Stimulation) Cardiomegalymodified fromSchulz R, J Am Coll Cardiol 2005 Tumor FormationMensah K & Yellon D, J Am Coll Cardiol 2005Ray KK & Cannon CP, J Am Coll Cardiol 2005 g. gioffrè
    28. 28. g. gioffrè
    29. 29. Periprocedural Myocardial Damage Atorvastatin PlaceboDi Sciascio, G. et al. J Am Coll Cardiol 2009;54:558-565 g. gioffrè
    30. 30. g. gioffrè
    31. 31. NAPLES II TRIAL CK-MB Increase Troponin I IncreaseBriguori, C. et al. J Am Coll Cardiol 2009;54:2157-2163 g. gioffrè
    32. 32.  Le statine hanno dimostrato un effetto protettivo nella rivascolarizzazione miocardica attraverso meccanismi indipendenti dalla riduzione dei valori del colesterolo. Quali statine utilizzare? g. gioffrè
    33. 33. N=502 CAD pts studied with IVUS +2.7%Plaque Volume (mm3) p=0.02 -0.4% CRP p<0.0001 CRP -5% -36%Nissen S et al, American Heart Association 2003 g. gioffrè
    34. 34. g. gioffrè
    35. 35. Primary and Secondary End PointsGibson, C. M. et al. J Am Coll Cardiol 2009;54:2290-2295 g. gioffrè
    36. 36. % 30 Atorvastatin Adjusted for LDL-C and CRP 25 Pravastatin 20 P=0.002 15 P=0.015 10 5 0 30-day TVR 2-year TVRGibson, C. M. et al. J Am Coll Cardiol 2009;54:2290-2295 g. gioffrè
    37. 37. • Coronary plaque reduction/ ↓ plaque progression• ↑ Myocardial threshold to exercise induced- ischemia (↑ coronary flow reserve/vasomotor function)• Biological plaque stabilization (↓ inflammation, ↓ local endothelial dysfunction, ↓ thrombogenicity)• ↑ Myocardial threshold to ischemic damage g. gioffrè
    38. 38.  Start statins (asap) before PCI (possibly 1 week before PCI). In naïve patients use a maximal loading dose (80 mg atorvastatin) before PCI. In patient already on statins, re-load the patients <12 before the procedure with high dose atorvastatin (80 mg) After PCI keep high dosage of statins (irrespective of cholesterol levels) and continue for 1-4 month. Then, tailor the dosage on the basis of LDL (and PCR) levels g. gioffrè
    39. 39.  Le statine hanno dimostrato un effetto protettivo nella rivascolarizzazione miocardica attraverso meccanismi indipendenti dalla riduzione dei valori del colesterolo. Tale meccanismo “cardioprotettivo” può essere utile nella chirurgia non cardiaca? g. gioffrè
    40. 40. Si può sfruttare questa“cardioprotezione” nellachirurgia non cardiaca? g. gioffrè
    41. 41. Lipid-Lowering Angiographic Trials Effect on Cardiovascular Events % 30 (10 trials, 942 placebo pts vs 924 statin pts, FU: 25 months) -26% 25 -21%Event Reduction 20 80% 15 79.36% 10 5 -0.8% 0 % Stenosis Cholesterol CV Events(Levine, Keaney & Vita N Engl J Med 1995) g. gioffrè
    42. 42. g. gioffrè
    43. 43. g. gioffrè
    44. 44. Incidence of Myocardial Ischemia and Troponin T Release LDL-Cholesterol ReductionFeringa H et al. J Am Coll Cardiol 2007;50:1649-1656 g. gioffrè
    45. 45. g. gioffrè
    46. 46. Kaplan-Meier Estimates of the Cumulative Probabilities of the Primary and Secondary OutcomesSchouten O et al. N Engl J Med 2009;361:980-989 g. gioffrè
    47. 47. Prevenzione FA e protezionerenale g. gioffrè
    48. 48. Gaetano GioffrèCardiologia Ospedale S. Eugenio, Roma gioffre.g@iol.it

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