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Tratamiento médico máximo de la isquemia miocárdica.

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Bloque: NUEVAS ESTRATEGIAS EN EL TRATAMIENTO DE LA CARDIOPATÍA ISQUÉMICA CRÓNICA.
Ponente: Dr. José Luis López Sendón
Curso Medicina Cardiovascular que tuvo lugar el 8 y 9 octubre de 2012 en Barcelona
Enlace: www.riesgocardiovascular.com

Published in: Health & Medicine
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Tratamiento médico máximo de la isquemia miocárdica.

  1. 1. Tratamiento médico máximo en Angina Estable
  2. 2. Nuevas estrategias en el médico máximo cardiopatía isquémica crónica! Tratamiento tratamiento de la en Angina Estable ! !Tratamieno médico máximo de la angina estable! José López-Sendón ! Hospital Universitario La Paz Madrid. Spain!
  3. 3. Tratamiento médico máximo en Angina Estable ESC!EHJ !2006;27:107!
  4. 4. Tratamiento médico máximo en Angina Estable The Future of CV Disease! Disability-Adjusted Life Years :! years of life lost due to premature death ! +! years of productive life lost due to disability! 1990! 2020! ! ! 47 million! 82 million!WHO Future CVD Atlas www.WHO.org 2009!
  5. 5. Tratamiento médico máximo en Angina Estable Cardiopatía isquémica crónica! n = 30.386 ! ! Mortalidad a 1 año: ! 1,48%!
  6. 6. Tratamiento médico máximo en Angina Estable Cardiopatía isquémica crónica! N = 33.241! Angina! Clase Funcional! Clase IV 1% ! Clase III! Clase I ! 18% ! 27% ! Clase II 54% !
  7. 7. Tratamiento médico máximo en Angina Estable
  8. 8. Tratamiento médico máximo en Angina Estable Estilo de vida! Cardiopatía ! isquémica crónica! Tratamiento!Fármacos ! Revascularización!
  9. 9. Tratamiento médico máximo en Angina Estable Cardiopatía isquémica crónica! n = 30.386 ! ! Angina basal 22%! Angina 1 año 16%!
  10. 10. Tratamiento médico máximo en Angina Estable ¿Por qué han mejorado los enfermos?!• Mejor estilo de vida!• Más fármacos!• Más revascularización!• Mejor cumplimiento de medicación!• Mejor selección de enfermos!• Mayor dosis!
  11. 11. Tratamiento médico máximo en Angina Estable Changes in risk factors profile over 1 year !  SBP>140  mmHg  and/or  DBP>90  mmHg  (without  DM)  and  SBP>130  mmHg  and/or  DBP>80  mmHg  (DM)    N  =  LDL  -­‐  22691/17385;  BP  -­‐  33221/29827;    BMI  -­‐  33209/26672;  DM  -­‐  33248/31539;  smoking  status  -­‐  33248/30791;  HR  (pulse)  -­‐  33223/29772  
  12. 12. Tratamiento médico máximo en Angina Estable Changes in CV medications over 1 year!
  13. 13. Tratamiento médico máximo en Angina Estable
  14. 14. Tratamiento médico máximo en Angina Estable ¿Dosis máxima?!• Recomendada en estudios?!• Tolerada hasta efectos secundarios?!• Curva J?!• Combinacion de farmacos mejor que dosismáxima?!
  15. 15. Tratamiento médico máximo en Angina Estable Treatments aimed at Improving Prognosis!Aspirin 75-150 mg od! Contraindications! Clopidogrel ! Statin! Intolerant / contraindications! Lower dose / alternative agent !ACEI in proven CVD!β-blocker in post MI !ESC Guidelines Stable Angina Eur Heart J. 2006; 27:1341!
  16. 16. Tratamiento médico máximo en Angina Estable Upgrade? Treatments aimed at Improving Prognosis!Aspirin 75-150 mg od! Contraindications!Ticagrelor ?, Prasugrel ?!Anti Xa?! Clopidogrel ! Statin! Intolerant / contraindications!Add a new lipid drug?! Lower dose / alternative agent !ACEI in proven CVD! Only if LVD / HF?!β-blocker in post MI ! Only if HF, HTA, arrythmias, Tachyc?!ESC Guidelines Stable Angina Eur Heart J. 2006; 27:1341!
  17. 17. Tratamiento médico máximo en Angina Estable Healthy life stile in primary prevention! Risk of Coronary Heart Disease!N=42.847 men, 40-75 y! No IHD in 1986! 16 y f-up!1- No smoking!2- Body mass < 25!3- Exercise > 30m/d!4- Healthy diet!5- Alcohol 5-30 g/dl!! Health Profesionals Follow-up Study. Circulation 2006;114:160
  18. 18. Tratamiento médico máximo en Angina Estable Effect of public smoking bans on incidence of MI ! Metaanalysis! Risk reduction: 19% Lightwood & Glantz, Circulation 2009
  19. 19. Tratamiento médico máximo en Angina Estable On-Treatment LDL-C & CHD Events in Statin Trials – Lower is Better! 30 4S - Placebo 25 Rx - Statin therapy! PRA – pravastatin! ATV - atorvastatin! Secondary Prevention! 4S - Rx 20Event rate (%) LIPID - Placebo 15 LIPID - Rx CARE - Placebo CARE - Rx CORONA - Placebo CORONA - Rx 10 HPS - Rx TNT – ATV10 PROVE-IT - PRA HPS - Placebo Primary Prevention TNT – ATV80 WOSCOPS – Placebo PROVE-IT – ATV AFCAPS - Placebo 5 AFCAPS - Rx WOSCOPS - Rx ASCOT - Placebo ASCOT - Rx 0 40! 60! 80! 100! 120! 140! 160! 180! 200! (1.0) (1.6) (2.1) (2.6) (3.1) (3.6) (4.1) (4.7) (5.2) LDL-C achieved mg/dL (mmol/L) Adapted from Rosensen RS. Exp Opin Emerg Drugs 2004;9(2):269-279! LaRosa JC et al. N Engl J Med 2005;352:1425-1435!
  20. 20. Tratamiento médico máximo en Angina Estable “J curve” between Blood Pressure and Coronary Artery Disease Patients with revascularizationINVEST ! Patients without revascularization22.500 pts!3y F-up! Hazard RatioJACC !2009; 54:1827!JAMA ! DBP (mmHg)2003;290:2805!
  21. 21. Tratamiento médico máximo en Angina Estable Survival according to HbA1c in Diabetics! Oral Antidiabetics Insulin 2.4 2.4 2.2 2.2 2.0 2.0HR (CI 95%) 1.8 1.8 1.6 1.6 1.4 1.4 1.2 1.2 1.0 1.0 0.8 0.8 0.6 0.6 6.0 6.5 7.0 7.5 8.0 8.5 9.0 9.5 10.0 10.5 11.0 6.0 6.5 7.0 7.5 8.0 8.5 9.0 9.5 10.0 10.5 11.0 HbA 1c (%) HbA 1c (%)Currie CJ, et al. Lancet 2010
  22. 22. Tratamiento médico máximo en Angina Estable Medical treatment for Chronic Angina / Ischemia! B-Blockers! Insufficient control of ischemia / angina! Contraindicated or intolerant! Add! Replace for!Ca Antagonist:!•  ! mlodipine: low heart rate, hipertension! A•  D ! iltiacem, Verapamil: Supraventricular tachicardia, hypertension. !Do not combine with b-blocker!Ivabradine: !Heart rate > 60 b/m!Nitrate: !General option! Consider cardiac cath & revascularization if high risk or persisting ischemia !
  23. 23. Tratamiento médico máximo en Angina Estable Beta-blocker DOSE important in Heart Failure? CIBIS II!Eur Heart J 2003;24:552!
  24. 24. Tratamiento médico máximo en Angina Estable Ivabradine in combination with Beta-Blockers! New indication! ! HR > 60 lpm!Ivabradine is indicated: -  in patients unable to tolerate or with a contraindication to beta-blockers -  or in combination with beta-blockers in patients inadequately controlled withan optimal dose and whose heart rate is > 60
  25. 25. Tratamiento médico máximo en Angina Estable Ivabradine associated with beta-blockers! Heart Rate > 60 bpm! (Basal Heart Rate 67 bpm) ! 60! P<0.001! P<0.001! Ivabradine + atenolol!Changes in exercise time 50! Placebo + atenolol! 40! (seconds) ! P<0.001! P<0.001! 30! 20! 10! 0! Time to! Total! Time to! Time to! 1 mm ST Exercise Time! Limiting Angina! Angina Onset ! depression ! Tardif, et al. Eur Heart J 2009;30:540!
  26. 26. Tratamiento médico máximo en Angina Estable Ranolazine! Authorisation valid through the European Union 9 July, 2008 2008 Na channel inhibitor!4.1 Therapeutic indications Ranexa is indicated as add-on therapy for the symptomatic treatment of patientswith stable angina pectoris who are inadequately controlled or intolerant to first-line antianginal therapies (such as betablockers and/or calcium antagonists).
  27. 27. Tratamiento médico máximo en Angina Estable Merlin: Patients with prior angina! CV death, MI or recurrent Ischemia ! Placebo (n = 1,776)! Ranolazine (n = 1,789)! i.v. 1,000 mg b.i.d. p.o.! 30 ! ! 29.4 29 ! P = 0.017! !Percentage (%)! 28 27 ! 26 ! ! 25.2 25 ! 24 ! 23 ! Wilson S.R. et al. JACC 2009;53:1510!
  28. 28. Tratamiento médico máximo en Angina Estable Ranolazine vs Placebo ! in patients with maximal tolerated BB and Ca Channel blockers! Changes in Exercise test Parameters ! at peak drug levels after 12 weeks of Treatment! 140! Placebo! 118! 120! Ranolazine! 100! 100! 90! seconds! 80! 73! 60! 44! 40! 32! 20! 0! Total! Time to! Time to 1 mm ST Exercise Time! Angina! depression!CARISA!Eur J Prev Cardiol 2012!
  29. 29. Tratamiento médico máximo en Angina Estable Conclusions!• High prevalence of Chronic angina!• Improve life stile / risk factor correction!• New drugs effective to reduce angina!• Optimize dose!• Role of revascularization? !
  30. 30. Tratamiento médico máximo en Angina Estable Ranolazine in Patients With Diabetes and CAD! Absolute Reduction in HbA1c From Baseline to Week 12! Ranolazine ! Placebo (n = 37) ! 750 mg b.i.d. (n = 47)! Mean Change From Baseline in HbA1c (%)! -0.02%! Baseline, mean HbA1c ! Ranolazine 7.9%! Placebo 7.5%! p = 0.008! -0.50%!Timmis AD, et al. Eur Heart J. 2006;27:42!
  31. 31. Tratamiento médico máximo en Angina Estable Incidence of angina! Framingham AHA, Heart Disease and Stroke Statistics, 2008 Update. NHLBI!Rosamond W, et al. Heart Disease and Stroke Statistics – 2008Update. Circulation 2008;117:e59.!
  32. 32. Tratamiento médico máximo en Angina Estable Who is responsible for !Cardiovascular Disease Prevention & Treatment?! ! The Good Old Days! Cardiologists! Other physicians!
  33. 33. Tratamiento médico máximo en Angina Estable Who is responsible for ! Cardiovascular Disease Prevention! ! The Brave New World! Cardiologists! Other physicians! The Patient himself!!Educators! Family! Health Authorities! Legislators! Health Care Providers!
  34. 34. Tratamiento médico máximo en Angina Estable •  Perception … may be misleading!•  Ischemic Heart Diasease: No Problem!•  Risk factors are not a problem!•  Someone else will take care of it!•  Well, revascularization solves the problem!•  New, better drugs replace the old ones!
  35. 35. Tratamiento médico máximo en Angina Estable Patients with angina (HR > 60 bpm) ! CV Death, hospitalization for MI or heart failure! 30! RR (95% IC), 0.76 (0.58–1.00), P=0.05! 25! 20! Placebo! %! 15! 24%! 10! Ivabradine! 5! 0! 0! 0.5! 1! 1.5! 2! Years!Fox K, et al. Eur Heart J. 2009;30:2337!
  36. 36. Tratamiento médico máximo en Angina Estable Heart Failure Death! 10 HR (95% IC), 0.74 (0.58–0.94), p=0.014 % Placebo - 26% 5 Ivabradine 0 0 6 12 18 24 30 Months Lancet. Online 29-08-2010!
  37. 37. Tratamiento médico máximo en Angina Estable Ranolazine: mechanism of action! Ischaemia ↑ Late INa Ranolazine Na+ overload NCX Ca++ overload Mechanical dysfunction O2 supply & demand Electrical dysfunction ↑Diastolic tension ↑ ATP consumption Arrhythmias ↓ Contractility ↓ ATP formation Hasenfuss G, Maier LS. Clin Res Cardiol 2008;97:222-26. NCX: sodium-calcium exchanger Maier LS. Cardiol Clin 2008;26:603-14.
  38. 38. Tratamiento médico máximo en Angina Estable Ranolazine: Key Clinical Trials! Total patients enrolled = 8,139 MARISA CARISA ERICA MERLINN=191 N=823 N=565 TIMI-36 N=6560Chronic Chronic Chronic Non-STEangina angina angina ACS Ranolazine Ranolazine Ranolazine Ranolazinevs placebo vs placebo vs placebo vs placebo on top of on top of on top of standard therapy amlodipine 10mg standard care ROLE N=746 Chronic angina Chaitman BR, et al. JAMA. 2004;291:309-316. Stone PH, et al. J Am Coll Cardiol. 2006;48:566-575. Morrow DA, et al. JAMA. 2007;297:1775-1783. J Am Coll Cardiol 2004;43:1375– 82
  39. 39. Tratamiento médico máximo en Angina Estable MARISA Efficacy Ranolazine vs Placebo! Placebo! Trough! 500 mg b.i.d.! Peak! 1,000 mg b.i.d.! 1,500 mg b.i.d.! 560! ***! ***! ***! ***! **! ***! 520!Time, sec! ***! ***! ***! ***! ***! 480! ***! ***! ***! ***! ***! ***! 440! **! 400! Exercise! Time! Time to 1-mm! Exercise! Time! Time to 1-mm! duration! to angina! ST-depression! duration! to angina! ST-depression!Chaitman BR. Circulation. 2006;113:2462-2472.!
  40. 40. Tratamiento médico máximo en Angina Estable Ranolazine vs Placebo ! in patients with maximal tolerated BB and Ca Channel blockers!CARISAsubgroup!in press!
  41. 41. Tratamiento médico máximo en Angina Estable MERLIN-TIMI 36: 
 Reduction in VT lasting ≥8 beats! 10 8.3% Placebo 8 RR 0.65 n = 3,189 P 0.001 RR 0.67 5.3% 6 P = 0.008 4 RanolazineIncidence (%) n = 3,162 2 RR 0.63 (0.52-0.76) P 0.001 0 0 24 48 72 96 120 144 168 Hours from randomization Scirica BM et al. Circulation. 2007;116: 1647-1652
  42. 42. Tratamiento médico máximo en Angina Estable Baseline BNP !and Effect of Ranolazine on Primary Endpoint ! CV Death, MI, or Recurrent Ischemia (%) BNP POS 30 Placebo 25 BNP POS p = 0.009 Ranolazine 20 BNP NEG 15 10 5 0 P-interaction = 0.05 0 180 360 Days from Randomization Morrow DA et al. AHA 2007, Orlando, FL!
  43. 43. Tratamiento médico máximo en Angina Estable Optimal Medical Treatment!NEJM 2007;356:1506!
  44. 44. Tratamiento médico máximo en Angina Estable Treatments aimed at Symptom Relief! β-blockers! Intolerant or contraindication! Symptoms not controlled after dose optimisation! Calcium antagonist or long- acting nitrate or K channel opener or If inhibitor ! Add calcium antagonist or long-acting nitrate! Intolerant! Symptoms not controlled after dose optimisation! Symptoms not controlled after dose optimisation! Ca antagonist or Combination of long-acting nitrate! nitrate and Ca antagonist or K- Consider suitability for channel opener ! revascularization ! Symptoms not controlled on 2 drugs after dose optimization!ESC Guidelines Stable Angina Eur Heart J. 2006; 27:1341!
  45. 45. Tratamiento médico máximo en Angina Estable Event free survival in stable angina and HT treated with Betablockers! Proportion event-free All-cause death 1.0 100! (p=0.4)! 0.8 80! Primary endpoint for efficacy
 (death, MI, RA, HF, CVA, PREV)
 Primary 0.6 60! p=0.5! endpoint for safety (death, MI, 0.4 40! Nifedipine! CVA, p=0.9)! Placebo! 0.2 20! RA != refractory angina! N=6779! PREV != peripheral revascularisation! 0.0 10! years 0! 2! Years ! 4! 6! 0 2 4 6 ACTION Lancet 2004;364, 849 !
  46. 46. Tratamiento médico máximo en Angina Estable Angina after ACS! Analysis from MERLIN-TIMI 36 trial; 5460 stable outpatients after ACS; 
 median follow-up of 12 months !reported at 4 months after ACS, 60! 50.2%! 50! 49.8% patients reported angina at 4 months after ACS! Rate of angina! 40! 29.5%! 30! % ! ! 20! 15.6%! 10! 4.7%! 0! No angina! Monthly! Weekly! Daily! angina! angina! angina! Arnold SV et al. Circ Cardiovasc Qual Outcomes. 2009;2:344-353!
  47. 47. Tratamiento médico máximo en Angina Estable Treatments aimed at Symptom Relief! Betablockers, 1st line treatment !Insuficient control of angina / ischaemia! Contraindication or intolerant! Add! Other option!Ca antagonists:!Amlodipine: Low heart rate, HT !!Diltiacem, verapamil: Tach, HT!! !Ivabradine: ! Heart rate! 60 b/m! ! !!! !Nitrate / Nicorandil: ! General option! !!! !Ranolazine: ! General option (diabetes, HF, arrhythmias) ! !!
  48. 48. Tratamiento médico máximo en Angina Estable Money talks! Heart and Stroke Statistical Update, AHA 2005!
  49. 49. Tratamiento médico máximo en Angina Estable •  Perception … may be misleading!•  Ischemic Heart Diasease: No Problem!•  Risk factors are not a problem!•  Someone else will take care of it!•  Well, revascularization solves the problem!•  New, better drugs replace the old ones!
  50. 50. Tratamiento médico máximo en Angina Estable PCI in Spain!
  51. 51. Tratamiento médico máximo en Angina Estable Survival Free of Death from Any Cause and Myocardial Infarction! 1.0! Optimal Medical Therapy (OMT)! 0.9! PCI + OMT! 0.8! 0.7! Hazard ratio: 1.05! 0.6! 95% CI (0.87-1.27)! P = 0.62! 0.5! 0.0! Number at Risk! 0! 1! 2! 3! 4! 5! 6! 7! Years! Medical Therapy 1138 1017 959 !834 ! 638 ! 408 ! 192 ! 30! PCI ! 1149 1013 952 !833 ! 637 ! 417 ! 200 ! 35!NEJM 2007;356:1506!
  52. 52. Tratamiento médico máximo en Angina Estable Angina Free! %!
  53. 53. Tratamiento médico máximo en Angina Estable •  Perception … may be misleading!•  Ischemic Heart Diasease: No Problem!•  Someone else will take care of it!•  Well, revascularizarion solves the problem!•  New, better drugs replace the old ones!
  54. 54. Tratamiento médico máximo en Angina Estable Conclusions!1- Take care of yourself!2- Follow Guidelines!3- Ivabradine and Ranolazine newdrugs for treatment of ischemia!4- Revasc complementary to meds!

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