REGRESION DE LA ATEROSCLEROSIS      ¿MITO O REALIDAD?    DR. ROBERTO LECARO PAZMIÑO      International Atherosclerosis Soc...
REGRESION DE LA ATEROSCLEROSIS      ¿MITO O REALIDAD?     DECLARACION DE INTERESES            NINGUNA
INFLAMACION Y ATEROSCLEROSIS Monocyte    HDL Inhibits Adhesion Molecule Expression                                        ...
EVOLUCION DE LA ATEROSCLEROSIS                                                         Ischemic Heart                     ...
REGRESION DE LA ATEROSCLEROSIS      ¿MITO O REALIDAD?       IMÁGENES EN ATEROSCLEROSIS  IVUS (ULTRASONOGRAFIA INTRAVASCUL...
ESTATINAS. EFECTOS PLEIOTROPICOS                                                      Estatinas   TXA2       t-PA       ...
REVERSAL   654 patients with symptomatic CAD with    angiographic stenosis >20% and LDL-C 125–210    mg/dL; 502 with eval...
REVERSAL                       Pravastatin 40 mg       Atorvastatin 80 mg        180                                 165. ...
REVERSAL                                    Prava                  Atorva                                              p=....
ASTEROID Trial507 patients > 18 years with angiographic evidence of CAD, excludingpatients using lipid-lowering medication...
ASTEROID                 Mean Mean during Percent              p                Baseline Treatment Change            Value...
ASTEROID                                Median Change in Percent                                            Median Change ...
REGRESION DE LA ATEROSCLEROSIS       ¿MITO O REALIDAD?1455 pacientes de 4 estudios con EAC y recibiendo estatinas .       ...
REGRESION DE LA ATEROSCLEROSIS       ¿MITO O REALIDAD?                  Nivel,Media(SD) [Media]*                 BASAL    ...
SATURN        4255 patients screened and 1578 patients treated at   centers in North America, Europe, South America and Au...
SATURN                              ATORVA        ROSU        Parameter                                       P Value     ...
SATURN             Median Change Percent Atheroma Volume                                  P=0.17† Change PercentAtheroma V...
Adverse Events: Safety Population (n=1385)                                                      Atorvastatin Rosuvastatin ...
LDL-C and Disease Progression Median Change PercentAtheroma Volume
Cholesterol Trialist Collaboration                                                     Meta-Analysis of Dyslipidemia Trial...
Cholesterol Trialist Collaboration      Meta-Analysis of Dyslipidemia Trials   170000 participants in 26 randomised trials...
ESTATINAS, PREVENCION PRIMARIA  METAANALISIS DE 27 ESTUDIOS (n = 174149), RIESGO A 5 AÑOS DE EvCM         Baseline risk (r...
¡NUEVA ESTATINA! PCKS9         ANTICUERPO MONOCLONAL HUMANO ESPECIFICO      PARA PROPROTEINA CONVERTASA SUBTILISIN/KEXIN 9...
Intima-Media Thickness of the Carotid Artery         during 24 and 14 Months of Therapy                                   ...
May 26,2011   ESTUDIO AIM-HIGH. NIACINA ER         DETENIDO A LOS 32 MESES• 3414 PACIENTES CON HISTORIA DE ECV, BAJO HDL  ...
INHIBIDORES DE LA CETPDALCETRAPID. Dal-PLAQUE                      (HDL +31%, ApoA1 +10%)   The Lancet - 12 September 2011...
DALCETRAPID. Dal-OUTCOMES     DETENIDO ESTUDIO POR FALTA         DE EFICACIA CLINICABasel, 7 May 2012Roche provides update...
ANTIINFLAMATORIOS, sPLA2,LpPLA2 Varespladib, a secretory phospholipase A2 enzyme  (sPLA2) inhibitor(Anthera)March 9, 2012...
FUTURAS INVESTIGACIONES ANTICUERPOS MONOCLONALES PARA P  SELECTINAS(SELECT ACS, SELECT CABG) INHIBIDORES DE INTERLUKINA ...
METOTREXATE (LDM) 15-20 mg/semana7000 PACIENTES POST IM CON DIABETESMELLITUS o SINDROME METABOLICO(INICIO MARZO 2013)PARA ...
REGRESION DE LA ATEROSCLEROSIS      ¿MITO O REALIDAD?                 CONCLUSIONES LAS ESTATINAS PRODUCEN REGRESION DE LA...
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Regresión de la arterosclerosis: ¿Mito o Realidad?

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Lecaro Roberto. Jornadas SOLACI 2012 , Ecuador. Puedes descargar gratis mas presentaciones de esta Jornada en la web oficial de SOLACI.

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Regresión de la arterosclerosis: ¿Mito o Realidad?

  1. 1. REGRESION DE LA ATEROSCLEROSIS ¿MITO O REALIDAD? DR. ROBERTO LECARO PAZMIÑO International Atherosclerosis Society American Heart Association American Stroke Association Vascular Biology Working Group American Society of Hypertension
  2. 2. REGRESION DE LA ATEROSCLEROSIS ¿MITO O REALIDAD? DECLARACION DE INTERESES NINGUNA
  3. 3. INFLAMACION Y ATEROSCLEROSIS Monocyte HDL Inhibits Adhesion Molecule Expression LDL Vessel LumenAdhesion EndotheliumMolecules MCP-1 LDL HDL Inhibit Oxidation Cytokines Modified LDL of LDL Foam Cell Macrophage Intima HDL Promotes Cholesterol Efflux Cockerill GW, Arterioscler Thromb Vasc Biol. 1995;15:1987-1994.
  4. 4. EVOLUCION DE LA ATEROSCLEROSIS Ischemic Heart Disease Cerebrovascular Disease Peripheral VascularLesion initiation Disease No  Symptomssymptoms Symptoms Time (y) Cockerill GW, Arterioscler Thromb Vasc Biol. 1995;15:1987-1994.
  5. 5. REGRESION DE LA ATEROSCLEROSIS ¿MITO O REALIDAD? IMÁGENES EN ATEROSCLEROSIS  IVUS (ULTRASONOGRAFIA INTRAVASCULAR)  CIMT (ENGROSAMIENTO IM CAROTIDEO)  MRI (RESONANCIA MAGNETICA)  PET/CT ( F-FLUORODEOXYGLUCOSA) Arsenault BJ. Curr Cardiol Rep 2012;14:443-449.
  6. 6. ESTATINAS. EFECTOS PLEIOTROPICOS Estatinas  TXA2  t-PA  Crecimiento  Rac1  RhoA  ET-1  PAI-1 del macrófago  Receptor AT1  MMPs  hs-PCR  ROS  NO  TF  Molécula de adhesión – – – + – – – – – –Activación Efecto Estabilidad Inflamación Hipertrofia Disfunción CML VasoconstricciónPlaquetaria Trombótico de placa vascular de CML Endotelial Proliferación  Hipertensión  Aterosclerosis Enfermedades Liao JK. Am J Cardiol 2005;96(suppl):24F-33F Cardiovasculares
  7. 7. REVERSAL 654 patients with symptomatic CAD with angiographic stenosis >20% and LDL-C 125–210 mg/dL; 502 with evaluable follow-up Randomization to pravastatin 40 mg/d or atrovastatin 80 mg/d for 18 months IVUS performed at baseline and 18 months Primary endpoint: percent change in atheroma volume assessed with IVUS Nissen SE et al. JAMA 2004;291:1071-1080.
  8. 8. REVERSAL Pravastatin 40 mg Atorvastatin 80 mg 180 165. 8 148. 160 4 140 118. 110. 120 4 1 91.8 100mg/dL 78.9 80 60 44.6 43.1 40 20 0 LDL-C Apo B-100 TG HDL-C Nissen SE et al. JAMA 2004;291:1071-1080.
  9. 9. REVERSAL Prava Atorva p=.01 5 4.4 p=.02% Cambios basales 4 p=.001 2.7 3 p=.02 p<.001 1.6 p<.001 2 p=.18 1 p=.98 p=.72 0.2 0 –0.4 -1 –0.9 -2 PF:Cambios volumen Total volumen % volumen ateroma (IVUS) ateroma ateroma Nissen SE et al. JAMA 2004;291:1071-1080.
  10. 10. ASTEROID Trial507 patients > 18 years with angiographic evidence of CAD, excludingpatients using lipid-lowering medication for more than 3 mos within theprevious 12 mos, uncontrolled triglyceride levels, and poorly controlleddiabetes.Prospective. Multicenter. International. Open Label. Treatment for 24mos. 292 patients with 613 matched stenoses at baseline and study end. Rosuvastatin 40 mg/day n=292 24 month treatment  Primary Endpoint: Rosuvastatin regression of coronary atherosclerosis by intravascular ultrasound (IVUS)  Secondary Endpoint: Rosuvastatin regression of coronary atherosclerosis by quantitative coronary angiography (QCA). Nissen SE et al. JAMA 2006;295:1556-1565.
  11. 11. ASTEROID Mean Mean during Percent p Baseline Treatment Change ValueCT (mg/dL) 204.0 133.8 –33.8 <0.001LDL-C (mg/dL) 130.4 60.8 –53.2 <0.001HDL-C (mg/dL) 43.1 49.0 +14.7 <0.001TG (mg/dL) 152.2 121.2 –14.5 <0.001LDL-C/HDL-C 3.2 1.3 –58.5 <0.001 Nissen SE et al. JAMA 2006;295:1556-1565.
  12. 12. ASTEROID Median Change in Percent Median Change in Atheroma Volume Most Diseased Subsegment 0,00 0Change in Percent Atheroma Change in Percent Atheroma -0,25 -2 Volume (mm3) Volume (%) -0,50 -4 -0,75 -6 –5.6 –0.79 -1,00 -8 Regression Regression p<0.001* p<0.001* *Wilcoxon signed rank test for comparison with baseline Nissen SE et al. JAMA 2006;295:1556-1565.
  13. 13. REGRESION DE LA ATEROSCLEROSIS ¿MITO O REALIDAD?1455 pacientes de 4 estudios con EAC y recibiendo estatinas . Ultrasonografia intravascular seriada (IVUS)REVERSAL CAMELOT ACTIVATE ASTEROID n=502 n=240 n=364 n=349 Seguimiento 18 or 24 meses  Puntos primarios: Cambios en los niveles de LDL-C and HDL-C y volumen del ateroma. Nicholls SJ, et al. JAMA. 2007; 297(5): 499-508.
  14. 14. REGRESION DE LA ATEROSCLEROSIS ¿MITO O REALIDAD? Nivel,Media(SD) [Media]* BASAL TRATAMIENTO Media (SD) PLDL-C 124.0 (38.3)[126.0] 87.5 (28.8) [85.6] -36.7 (41.1) <0.001HDL-C 42.5 (11.0) [41.0] 45.1 (11.4) [43.7] 2.6 (6.7) <0.001LDL/HDL 3.0 (1.1) [3.0] 2.1 (0.9) [1.9] -1.0 (1.1) <0.001% volum. 39.7 (9.8) [40.0] 40.1 (9.7) [40.1] 0.5 (3.9) 0.001ateromaVolumen 186.8 184.4 -2.4ateroma <0.001 (79.5) [176.2] (78.2) [174.3] (23.6)Total,mm3 Nicholls SJ, et al. JAMA. 2007; 297(5): 499-508.
  15. 15. SATURN 4255 patients screened and 1578 patients treated at centers in North America, Europe, South America and Australia Treatment for 2 weeks with atorvastatin 40 mg or rosuvastatin 20 mg for 2 weeks to achieve LDL-C <116 mg/dLAtorvastatin 80 mg (n=691) 24 months treatment Rosuvastatin 40 mg (n=694)346 (25%) patients withdrew or did not have an evaluable final IVUS Follow-up IVUS of originally imaged “target” vessel (n=1039) Nicholls SJ. N Engl J Med 2011;365:2078-87
  16. 16. SATURN ATORVA ROSU Parameter P Value (n=519) (n=520)LDL cholesterol (mg/dL) 70.2 62.6 <0.001HDL cholesterol (mg/dL) 48.6 50.4 0.01Triglycerides (mg/dL)* 110 120 0.02LDL:HDL cholesterol 1.5 1.3 <0.01hsCRP (mg/L)* 1.0 1.1 0.05 Nicholls SJ. N Engl J Med 2011;365:2078-87
  17. 17. SATURN Median Change Percent Atheroma Volume P=0.17† Change PercentAtheroma Volume -0.99 -1.22 P<0.001* P<0.001* † comparison between groups. * comparison from baseline Nicholls SJ. N Engl J Med 2011;365:2078-87
  18. 18. Adverse Events: Safety Population (n=1385) Atorvastatin Rosuvastatin Parameter (n=691) (n=691)Major cardiovascular event 7.1% 7.5%ALT >3x ULN† 2.0% 0.7%CK >5x ULN 0.7% 0.3%Proteinuria* 1.7% 3.8%Creatinine >ULN 3.0% 3.3%Change HbA1c (%) 0.09 0.05† P=0.04 and * P=0.02 for comparison between groups Nicholls SJ. N Engl J Med 2011;365:2078-87
  19. 19. LDL-C and Disease Progression Median Change PercentAtheroma Volume
  20. 20. Cholesterol Trialist Collaboration Meta-Analysis of Dyslipidemia Trials 170000 participants in 26 randomised trials of statins Major Vascular Events 50%Proportional Reduction in Event Rate (SE) 40% 30% 20% 10% 1 mmol/L = - 22% 0% 2-3 mmol/L = - 40-50% 0.5 1.0 1.5 2.0 10% Reduction in LDL Cholesterol (mmol/L) CTT Collaborators. Lancet. 2010; 376:1670-81
  21. 21. Cholesterol Trialist Collaboration Meta-Analysis of Dyslipidemia Trials 170000 participants in 26 randomised trials of statins  ESTATINAS DISMINUYEN EL RIESGO DE ECV INDEPENDIENTE DEL NIVEL BASAL DE LDL-C Y CARACTERISTICAS DEL PACIENTE  CADA - 39 mg/dl (1 mmol/L) de LDL-C - 22% EVM (ECC,Stroke) - 10% Mortalidad total (-ECV ) - No cáncer  ALTAS DOSIS DISMINUYE EL RIESGO DE ECV MEJOR QUE BAJAS DOSIS CTT Collaborators. Lancet. 2010; 376:1670-81
  22. 22. ESTATINAS, PREVENCION PRIMARIA METAANALISIS DE 27 ESTUDIOS (n = 174149), RIESGO A 5 AÑOS DE EvCM Baseline risk (risk of CV Risk reduction (95% CI) per event over five years), % 1-mmol LDL reduction <5 0.57 (0.36-0·89) 5-10 0.61 (0.50-0·74) 10-20 0.77 (0.69-0·85) 20-30 0.77 (0.71-0·83) ≥ 30 0.78 (0.72-0·84) Overall 0.76 (0.73-0·79)CTT Collaborators. Lancet 2012; DOI:10.1016/S0140-6736(12)60367-5 376:1670-81
  23. 23. ¡NUEVA ESTATINA! PCKS9 ANTICUERPO MONOCLONAL HUMANO ESPECIFICO PARA PROPROTEINA CONVERTASA SUBTILISIN/KEXIN 9 Intervención LDL–C basal Cambios (mg/dL) LDL-C (%) Placebo 130.2 -5.1 REGN727 50 mg, cada 2 sem. 123.2 -39.6 REGN727 100 mg, cada 2 sem. 127.0 -64.2REGN727 150 mg SC, cada 2 sem. 123.9 -72.4 REGN727 200 mg, cada 4 sem. 128.2 -43.2 REGN727 300 mg, cada 4 sem. 131.6 -47.7 Mckenney JM. J Am Coll Cardiol 2012; 59: 2344-2353
  24. 24. Intima-Media Thickness of the Carotid Artery during 24 and 14 Months of Therapy ARBITER-6 HALTS ENHANCE-TrialKastelein J et al. N Engl J Med 2008;358:1431-1443 Taylor A et al. N Engl J Med 2009;361:2113-2122
  25. 25. May 26,2011 ESTUDIO AIM-HIGH. NIACINA ER DETENIDO A LOS 32 MESES• 3414 PACIENTES CON HISTORIA DE ECV, BAJO HDL Y ALTOS TG CON LDL META 71 mg/dl (ESTATINA)• NIACINA ER 2 G/DIA VS PLACEBO• PUNTOS FINALES: IM FATAL Y NO FATAL,STROKE, SCA O REVASCULARIZACION• RESULTADOS: PTOS.FINALES FRECUENCIA ANUAL NIACINA 5.8%(262),PLACEBO 5.6%(249).RR 1.05• 20% DE AUMENTO DE HDL Y 25% REDUCCION TG• STROKE: NIACINA 1.6%, PLACEBO 0.7%
  26. 26. INHIBIDORES DE LA CETPDALCETRAPID. Dal-PLAQUE (HDL +31%, ApoA1 +10%) The Lancet - 12 September 2011DOI: 10.1016/S0140-6736(11)61383-4
  27. 27. DALCETRAPID. Dal-OUTCOMES DETENIDO ESTUDIO POR FALTA DE EFICACIA CLINICABasel, 7 May 2012Roche provides update on Phase III study of dalcetrapibRoche (SIX: RO, ROG; OTCQX: RHHBY) today announced thatfollowing the results of the second interim analysis of thedalcetrapib dal-OUTCOMES Phase III trial, the independent Dataand Safety Monitoring Board (DSMB) has recommendedstopping the trial due to a lack of clinically meaningfulefficacy. The dal-OUTCOMES trial evaluated the efficacy andsafety profile of dalcetrapib when added to existing standard ofcare in patients with stable coronary heart disease (CHD)following an acute coronary syndrome (ACS). No safety signalsrelating to the dal-OUTCOMES trial were reported from the DSMB
  28. 28. ANTIINFLAMATORIOS, sPLA2,LpPLA2 Varespladib, a secretory phospholipase A2 enzyme (sPLA2) inhibitor(Anthera)March 9, 2012Anthera detiene VISTA-16 Clinical Study debido a perdida deEFICACIA siguiendo las recomendaciones del independienteData Safety Monitoring BoardVISTA-16 , 6500 patients con ACS,varespladib 500 mg /dia oplacebo por 16 semanas + atorvastatin +cuidados estandares. Lipoprotein-associated phospholipase A2 (Lp-PLA2) inhibitor darapladib (GlaxoSmithKline).STABILITY (Stabilizacion of Atherosclerotic Plaque by Initiationof Darapladib Therapy trial), estudio con 15000 pacientes paraser completado en Agosto del 2013SOLID TIMI-52 (Stabilizacion of Plaque Using Darapladib-Thrombolysis in Myocardial Infarction 52 trial en Abril 2014
  29. 29. FUTURAS INVESTIGACIONES ANTICUERPOS MONOCLONALES PARA P SELECTINAS(SELECT ACS, SELECT CABG) INHIBIDORES DE INTERLUKINA 1β (IL 1 β) ESTUDIO CANTOS ( Canakinumab Anti- Inflammatory Thrombosis Outcomes Study) Antagonistas MicroRNA 33a, MicroRNA 33b Arsenault BJ. Curr Cardiol Rep 2012;14:443-449.
  30. 30. METOTREXATE (LDM) 15-20 mg/semana7000 PACIENTES POST IM CON DIABETESMELLITUS o SINDROME METABOLICO(INICIO MARZO 2013)PARA EFECTOS COLATERALES,ACIDOFOLICO 1.2 mg 6 dias/semanaPUNTOS FINALES PRIMARIOS: TIEMPOPARA EL 1ER EVENTO CV. (Compuesto demuerte CV, IM y stroke no fatal) NHLBI 2012.
  31. 31. REGRESION DE LA ATEROSCLEROSIS ¿MITO O REALIDAD? CONCLUSIONES LAS ESTATINAS PRODUCEN REGRESION DE LAATEROSCLEROSIS Y LA DISMINUCION DE EVENTOSCARDIOVASCULARES ,ES INDEPENDIENTE DEL NIVELBASAL “NORMAL” DE LDL LA EZETIMIBA NO DEMUESTRA REGRESIONNI REDUCCION DE EVENTOS CARDIOVASCULARES TORCETRAPID, DALCETRAPID (INHIBIDORES CETP)Y LA NIACINA ,VARESPLADIB NO REDUCEN EVENTOS CV PCSK9,ANTIINFLAMATORIOS,MICRO RNAs

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