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Terapeutica 1 dislipidemia
- 1. Epidemia Mundial de la vida moderna Aterosclerosis
- 2. Incidencia de eventos vasculares coronarios, cerebrales y periféricos __de tipo Isquémico Objetivos Fundamentales de las Guías Norteamericanas Consenso Mexicano de Lípidos OMSEuropeas Control óptimo de los factores mayores de riesgo cardiovascular Promover estilos de vida saludable Prevenir la discapacidad y la muerte prematura Conocer y utilizar fármacos probados en la prevención y tratamiento de __las enfermedades cardiovasculares
- 3. ¿ Son las Guías del ATP-III¿ Son las Guías del ATP-III vigentes ?vigentes ? NECP
- 4. Programa Nacional de Educación sobre el Colesterol (National Cholesterol Education Program) Lineamientos del III Panel de Tratamiento en Adultos (Adult Treatment Panel III, ATP III) Guidelines
- 5. Nuevos Equivalentes de Enfermedad Coronaria >20% de riesgo a 10años de enfermedad coronaria (Framingham) Diabetes Otras formas de enfermedad aterosclerótica clínica: – – Enfermedad arterial Periférica – – Aneurisma aórtico abdominal – – Enfermedad carotídea
- 8. Nuevas Directrices: Diagnóstico Col-LDL ( mg/dl ) • < 100 óptima • 100-129 subóptimo • 130-159 limítrofe alto • 160-189 alto • ≥ 190 muy alto Col. Total ( mg/dl ) • < 200 deseable • 200-239 limítrofe alto • > 240 alto Col- HDL ( mg/dl ) • < 40 bajo • > 60 * alto * Factor de riesgo “negativo” Clasificación: A dult T reatment P anel III N C E P
- 9. TRIGLICERIDOS: (mg/dl) • < 150< 150 normalnormal • 150-199150-199 limítrofe altolimítrofe alto • 200-499200-499 altoalto • > 500> 500 muy altomuy alto Factor de riesgo independiente para EACFactor de riesgo independiente para EAC Otras situaciones predisponentes:Otras situaciones predisponentes: Diabetes Mellitus, Sx. Nefrótico, hepatopatías, alcoholismo, tabaquismo, fármacosDiabetes Mellitus, Sx. Nefrótico, hepatopatías, alcoholismo, tabaquismo, fármacos (esteroides(esteroides).). Nuevas Directrices: Diagnóstico
- 10. Diagnóstico y Estratificación de Riesgo Estratificación del Riesgo Coronario • Adultos > 20 años • Perfil completo de lípidos: CT, LDL, HDL y TG. • Cada 5 años • NCEP, Adult Treatment Panel III. JAMA. 2001;285:2486-2497.
- 11. Categorías de Tratamiento, LDL-C Metas y Puntos de Corte Categoría del Riesgo Meta LDL-C Terapia con Fármaco Enfermedad Coronaria o Equivalente de riesgo <100 mg/dL ≥130 mg/dL* ≥ 2 Factores de Riesgo Riesgo a 10 años 10–20% Riesgo a 10 años <10% <130 mg/dL <130 mg/dL ≥130 mg/dL ≥160 mg/dL < 2 Factores de Riesgo <160 mg/dL ≥190 mg/dL * 100–129 mg/dL = después de cambios de estilo de vida, considerar estatinas, niacina, o fibratos
- 14. ATP III: El Síndrome MetabólicoATP III: El Síndrome Metabólico El diagnóstico se establece en presencia de ≥ 3 componentes Factor de Riesgo Nivel Definido Obesidad Abdominal (Circunferencia de la cintura) Hombre Mujer >102 cm (>40 in) >88 cm (>35 in) TG ≥150 mg/ dL HDL-C Hombre Mujer <40 mg/ dL <50 mg/ dL Presión Sanguínea ≥130/≥85 mm Hg Glucosa en ayuno ≥110 mg/dL
- 18. ~10% Pérdida de Peso = ~30% Pérdida de Tejido Adiposo Visceral
- 19. *IM fatal o no fatal; **eventos isquémicos Puntos finales con Estatinas Estudios Fármaco Reducción del Riesgo Coronario Prevención Primaria AFCAPS/TexCAPS Lovastatin –40%* WOSCOPS Pravastatin –31%* Prevención Secundaria 4S Simvastatin –34%* CARE Pravastatin –24%* LIPID Pravastatin –24%* Isquemia MIRACL Atorvastatin –26%** AVERT Atorvastatin –36%**
- 20. Estudios clínicos posteriores al ATP III HPS (simvastatin 40) PROSPER (pravastatin 40) ALLHAT-LLT (pravastatin 40) ASCOT-LLA (atorvastatin 10) PROVE IT (pravastatin 40 vs. atorvastatin 80)
- 21. Estudio de Protección del Corazón: Resultados Importantes Reducción del riesgo en todos los niveles de LDL-C Reducción del riesgo en LDL-C <100 mg/dL Beneficio en pacientes ancianos Beneficio en pacientes diabéticos
- 22. Reducción de Eventos Vasculares de Acuerdo a niveles LDL-C (mg/dL) %ReducciónRelativadelRiesgo LDL-CLDL-C <100<100 LDL-CLDL-C 100–130100–130 LDL-CLDL-C >130>130 -22%-22% -30%-30% -22%-22% -45 -30 -15 0
- 23. Estudio Prove-it 4,162 pacientes con síndrome coronario agudo Tratamiento: pravastatina 40 mg vs. atorvastatina 80 mg Niveles de LDL-C con tratamiento: pravastatina 95 mg/dL, atorvastatina 62 mg/dL 2 años continuos de seguimiento 16% de reducción en los puntos finales compuestos con atorvastatina comparado con pravastatina
- 24. Estudio de Protección del Corazón (5 años) 0 1 Riesgo de evento coronario 100 LDL-C (mg/dL) Simvastatina 40 mg 60 26% Reducción de eventos 22% Reducción de eventos Simvastatina 40 mg
- 25. “Más bajo es mejor” Riesgo Relativo de evento coronario (Log Scale) 3.7 2.9 2.2 1.7 1.3 1.0 LDL-C (mg/dL) 40 70 100 130 160 190 0 1
- 26. Candidatos a Metas Muy Bajas de LDL-C: < 70 mg/dL Pacientes de muy alto riesgo – Enfermedad Aterosclerosa establecida + multiples factores de riesgo (diabetes) + factores mayores de riesgo mal controlados (tabaquismo) + síndrome metabólico (TG altos, HDL-C bajo) + síndromes coronarios agudos (Prove-it)
- 27. ¿Qué hay de nuevo para pacientes con riesgo moderadamente alto? Meta ATP III LDL-C : <130 mg/dL Nivel LDL-C ≥130 mg/dL: comenzar con fármacos y tratamiento dietético Nueva opción terapéutica: Meta de LDL-C <100 mg/dL (basada en ASCOT) Nivel de LDL-C 100–129 mg/dL: terapia opcional con fármacos (basada en ASCOT)
- 28. ¿Que hay de Nuevo para los Pacientes de Alto Riesgo? Meta de ATP III LDL-C : <100 mg/dL – Para riesgo muy alto: meta opcional <70 mg/dL – Para LDL-C ≥100 mg/dL, comenzar con el fármaco reductor de LDL simultaneamente con cambios en el estilo de vida – Para LDL-C <100 mg/dL, fármaco reductor de LDL es una opción terapéutica – Para TG altos/HDL-C bajo, considerar fibratos o ácido nicotínico con fármaco reductor de LDL
- 29. EZETIMIBA ASOCIADA A SIMVASTATINA • Doble Inhibición:
- 30. DOBLE INHIBICION
- 31. NUEVAS GUIAS ACC/AHA 2013 PARA EL MANEJO DE LAS HIPERLIPIDEMIAS • Los principales cambios planteados en las nuevas guías: • 1. Todas las recomendaciones se basan en estudios randomizados basados en la evidencia. • 2. prioridad a uso de estatinas de alta y mediana intensidad • 3, Define 4 grupos de sujetos que se benefician son el uso de estatinas • 4. Desecha el uso de objetivos de niveles de colesterol LDL o colesterol no HDL en el tratamiento de la hipercolesterolemia • 5. Se incluye al accidente vascular encefálico y a la crisis isquémica transitoria a los tradicionales eventos ateroescleróticos coronarios. • 6. desaconseja el tratamientos con otros fármacos “ no- estativas” salvo que el exista intolerancia demostrada a las estatinas. • 7. Excluye de la terapia con estatinas a pacientes con ICC clase funcional III o IV y pacientes con hemodiálisis
- 32. ALTA INTENSIDAD MODERDA INTENSIDAD Reducción aproximada del colesterol LDL >50 % 30 -49% Grupo I Enfermedad ateroesclerótica cardiovascular < 75 años Enfermedad ateroesclerótica cardiovascular > 75 años Grupo II LDL > 190 mg/dl LDL > 190 mg/dl si no tolera dosis alta de estatina Grupo III Diabetes ,edad: 40 -75 años LDL: 70 -189 mg/dl Riesgo 10 años > 7,5 % Diabetes, edad. 40 -75 años LDL: 70 -189 mg/dl Riesgo 10 años < 7,5 % Grupo IV No diabetes, edad: 40 -75 años LDL: 70 -189 mg/dl Riesgo 10 años > 7,5% No diabetes, edad: 40 -75 años LDL: 70 -189 mg/dl Riesgo a 10 años < 7,5 % Estatinas Atorvastatina: 40, 80 mg Rosuvastatina 20 mg Atorvastatina: 10,20 mg Rosuvastatina 10 mg Sinvastatina 20 -40 mg Pravastatina: 40, 80 mg
Notas del editor
- ATP III: the metabolic syndrome The NCEP ATP III guidelines define 5 components of the metabolic syndrome; 3 or more risk factors are required for the diagnosis of the metabolic syndrome. The low HDL-C criterion for women is higher than that defined for risk factor counting in the ATP III algorithm for primary prevention, and the blood pressure criterion is lower. A comparison of the ATP III risk factor–counting algorithm and the metabolic syndrome is given in the next two slides. Reference: Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive summary of the third report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA 2001;285:2486-2497.
- Post–ATP III clinical trials Since the ATP III guidelines were published, a number of large clinical event trials of statin therapy have been published, including the Heart Protection Study (HPS), Prospective Study of Pravastatin in the Elderly at Risk (PROSPER), Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial—Lipid-Lowering Trial (ALLHAT-LLT), Anglo-Scandinavian Cardiac Outcomes Trial—Lipid Lowering Arm (ASCOT-LLA), and Pravastatin or Atorvastatin Evaluation and Infection Therapy (PROVE IT). References: Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20 536 high-risk individuals: a randomised placebo-controlled trial. Lancet 2002;360:7-22. Shepherd J, Blauw GJ, Murphy MB, et al., on behalf of the PROSPER study group. Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial. Lancet 2002;360:1623-30. ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. Major outcomes in moderately hypercholesterolemic, hypertensive patients randomized to pravastatin vs usual care: the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT-LLT). JAMA 2002;288:2998-3007. Sever PS, Dahlöf B, Poulter NR, et al., for the ASCOT Investigators. Prevention of coronary and stroke events with atorvastatin in hypertensive patients who have average or lower-than-average cholesterol concentrations, in the Anglo-Scandinavian Cardiac Outcomes Trial—Lipid Lowering Arm (ASCOT-LLA): a multicentre randomised controlled trial. Lancet 2003;361:1149-1158. Cannon CP, Braunwald E, McCabe CH, et al. Comparison of intensive and moderate lipid lowering with statins after acute coronary syndromes. N Engl J Med 2004;350:1495-1504.
- Heart Protection Study: major findings HPS demonstrated the clinical benefit of LDL-C–lowering simvastatin therapy regardless of baseline LDL-C, including LDL-C levels already at the goal recommended in the ATP III guidelines. In addition, benefit was observed in older patients and in patients with diabetes. References: Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20 536 high-risk individuals: a randomised placebo-controlled trial. Lancet 2002;360:7-22. Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol-lowering with simvastatin in 5963 people with diabetes: a randomised placebo-controlled trial. Lancet 2003;361:2005-2016.
- HPS: reduction in major vascular events according to baseline LDL-C (mg/dL) In HPS, simvastatin treatment reduced relative risk for major vascular events in patients whose baseline LDL-C was &gt;130 mg/dL, 100–130 mg/dL, or &lt;100 mg/dL. References: Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20 536 high-risk individuals: a randomised placebo-controlled trial. Lancet 2002;360:7-22. MRC/BHF Heart Protection Study website: http://www.hpsinfo.org
- PROVE IT In the Pravastatin or Atorvastatin Evaluation and Infection Therapy trial (PROVE IT), more than 4,000 patients with acute coronary syndrome and total cholesterol of 240 mg/dL or less (200 mg/dL in patients on lipid therapy) were randomized to receive intensive therapy with atorvastatin 80 mg/d or moderate therapy with pravastatin 40 mg/d. Intensive therapy reduced LDL-C to 62 mg/dL and reduced the composite primary endpoint (death, myocardial infarction, unstable angina requiring rehospitalization, revascularization after 30 days, and stroke) by 16% compared with moderate therapy, which reduced LDL-C to 95 mg/dL (within the LDL-C goal of &lt;100 mg/dL recommended in the ATP III guidelines). Reference: Cannon CP, Braunwald E, McCabe CH, et al. Comparison of intensive and moderate lipid lowering with statins after acute coronary syndromes. N Engl J Med 2004;350:1495-1504.
- Heart Protection Study (5-year trial) Since the ATP III guidelines were published, evidence from HPS was not supportive of the threshold model and has suggested that the relationship between LDL-C level and CHD risk is curvilinear (or possibly linear) across the full range of baseline LDL-C levels included in the study. In HPS, similar benefit on cardiovascular event reduction was provided with simvastatin therapy in patients whose baseline LDL-C was above or below the ATP III goal of 100 mg/dL. Reference: Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20 536 high-risk individuals: a randomised placebo-controlled trial. Lancet 2002;360:7-22.
- &quot;The lower, the better&quot; The results of HPS and PROVE IT suggest that reducing LDL-C substantially below 100 mg/dL may provide additional benefit in high-risk patients. Neither of these trials indicated a lower threshold for LDL-C below which further LDL-C reduction did not provide further risk reduction. Reference: Grundy SM, Cleeman JI, Bairey Merz CN, et al., for the Coordinating Committee of the National Cholesterol Education Program. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. Circulation 2004;110:227-239.
- Candidates for very low LDL-C goal of &lt;70 mg/dL Determining whether high-risk patients would benefit from the more intensive LDL-C goal of &lt;70 mg/dL requires clinical judgment. Appropriate candidates would be very high risk patients such as those with established CHD or other atherosclerotic vascular disease, multiple risk factors, severe or poorly controlled risk factors, metabolic syndrome, or acute coronary syndromes.
- What’s new for moderately high risk patients? On the basis of clinical trial evidence published since the ATP III guidelines, recommended modifications to the ATP III treatment algorithm for patients with moderately high risk (2 or more risk factors and estimated 10-year risk of 10–20%) include initiation of LDL-C–lowering drug therapy if LDL-C remains 130 mg/dL or greater with diet therapy (with an LDL-C goal of &lt;130 mg/dL as in ATP III) and a therapeutic option of initiating LDL-C–lowering drug therapy in patients whose LDL-C is 100–129 mg/dL (at baseline or on diet therapy) to reduce LDL-C to &lt;100 mg/dL.
- What’s new for high-risk patients? On the basis of clinical trial evidence published since the ATP III guidelines, recommended modifications to the ATP III treatment algorithm for high-risk patients (CHD or CHD risk equivalent) include an optional LDL-C goal of &lt;70 mg/dL for very high risk patients, simultaneous initiation of LDL-C–lowering drug therapy with therapeutic lifestyle changes in patients with LDL-C 100 mg/dL or greater, and the option of LDL-C–lowering drug therapy in patients with LDL-C &lt;100 mg/dL at baseline. In high-risk patients with high triglycerides or low HDL-C, a fibrate or nicotinic acid may be considered in combination with an LDL-C–lowering drug.