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Novedades en el manejo de la Insuficiencia Cardiaca Crónica

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Presentación utilizada por el Dr. Domingo Pascual Figal en el directo online ‘Lo mejor en Insuficiencia Cardiaca de ESC Múnich 2018’, realizado el 19 de septiembre de 2018 en la Casa del Corazón

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Novedades en el manejo de la Insuficiencia Cardiaca Crónica

  1. 1.  Epidemiología  Transición tras hospitalización  IC preservada  Comorbilidades  Metanálisis y vida real  Redefinición de daño miocárdico
  2. 2. PATIENTS’ JOURNEY OF CARE FOLLOWING INCIDENT HF: diagnostic test, treatments and care pathways in 93,000 patients Conrad N, et al. Lancet. 2018; 391: 572-580
  3. 3. Conrad N, et al. Lancet. 2018; 391: 572-580 PATIENTS’ JOURNEY OF CARE FOLLOWING INCIDENT HF: diagnostic test, treatments and care pathways in 93,000 patients
  4. 4. Conrad N, et al. Lancet. 2018; 391: 572-580 PATIENTS’ JOURNEY OF CARE FOLLOWING INCIDENT HF: diagnostic test, treatments and care pathways in 93,000 patients
  5. 5. CLCZ696B2401 study A multicenter, randomized, open label, parallel group study comparing Two modalities of tReatment with LCZ696 in heArt failure patieNtS with reduced ejectIon-fracTion hospItalized for an acute decOmpensation eveNt (ADHF) - the TRANSITION study
  6. 6. Data on-file
  7. 7. Session Title Date & Time Poster Session 1: Chronic heart failure – Pathophysiology and mechanisms Poster # P886 Initiation of sacubitril/valsartan in hospitalized patients with heart failure with reduced ejection fraction after hemodynamic stabilization: primary results of the TRANSITION study Sat 25 Aug 11:00-16:00 Poster Session 7: Chronic heart failure – Treatment Poster # P6531 Initiation of sacubitril/valsartan in hospitalized patients with HFrEF after hemodynamic stabilization: baseline characteristics of the TRANSITION study compared with TITRATION and PARADIGM-HF Tue 28 Aug 14:00-18:00 TRANSITION Investigators in Munich: 10 weeks results presentation and discussion Sat 25 Aug 06:45-08:15am
  8. 8. Life-time risk after a first hospitalization ADHF Median time from hospital discharge Readmissionrate Initial discharge Death Transition phase Plateau phase Palliation and priorities Picture from: Desai AS and Stevenson LW. Circulation. 2012; 126(4): 501-506
  9. 9. Key eligibility criteria for TRANSITION, PARADIGM-HF and TITRATION studies Variable TRANSITION PARADIGM-HF TITRATION Age ≥18 years NYHA class II-IV LVEF ≤40% ≤40%a ≤35% Plasma BNP or NT-proBNP levels No pre-defined entry levels (BNP ≥150 pg/mL or NT-proBNP ≥600 pg/mL) or (BNP ≥100 pg/mL or NT-proBNP ≥400 pg/mL and hospitalization for HF within last 12 months) No pre-defined entry levels SBP ≥110 mmHg ≥100 mmHg ≥100 mmHg eGFR ≥30 mL/min/1.73 m2 Clinical status Inpatients Outpatients Inpatients and outpatients Previous ACEI/ARB dose Variable doses of ACEI/ARB or treatment naïveb Stable dose of an ACEI/ARB equivalent to enalapril 10 mg/day for at least 4 weeks before the screening Variable doses of ACEI/ARB or treatment naïveb,c ACEI, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker; BNP, B-type natriuretic peptide; eGFR, estimated glomerular filtration rate; HF, heart failure; LVEF, left ventricular ejection fraction; NYHA, New York Heart Association; NT-proBNP, N-terminal pro- B-type natriuretic peptide; SBP, systolic blood pressure a LVEF eligibility criteria was changed to ≤35% in a protocol amendment; b ACEI/ARB naïve defined as patients without any previous ACEI/ARB for ≥4 weeks before hospital admission; c For outpatients, ACEI/ARB dose must have been stable for at least 2 weeks Clinicaltrials.gov identifier: NCT02661217. ESC Congress, Munich, 2018. P6531
  10. 10. TRANSITION: Flexibility similar to the clinical practice HF treatment optimization in hospitalized patients with HFrEF stabilized after an ADHF event* Optimization of guidelines recommended HF therapies* at the discretion of the investigator Recruiting hospitalized HFrEF patients: • On any dose of ACEI/ARB • Naive to ACEI/ARB • De novo = newly diagnosed Up-titration and down- titration of sacubitril/valsartan according to patient tolerability *Beta-blockers, MRAs, and replacement of ACEi/ARB by sacubitril/valsartan ACEi, angiotensin converting enzyme inhibitor; ADHF, acute decompensated heart failure; ARB, angiotensin receptor blocker; b.i.d, twice daily; HF, heart failure; OMT, optimal medical treatment for HF; sac/val, sacubitril/valsartan Pascual-Figal, et al. ESC Heart Failure (Epub ahead of print)
  11. 11. TRANSITION study design ACEi, angiotensin converting enzyme inhibitor; ADHF, acute decompensated heart failure; ARB, angiotensin receptor blocker; b.i.d, twice daily; HF, heart failure; OMT, optimal medical treatment for HF; sac/val, sacubitril/valsartan Treatment epoch 10 weeks’ duration starting at randomization 1-3 days’ screening epoch 16 weeks’ follow-up epoch Open-label Sac/val 50 mg  100 mg b.i.d.  200 mg b.i.d. or Sac/val  100 mg  200 mg b.i.d. as per label and at investigator discretion Open-label Sac/val 50 mg  100 mg b.i.d.  200 mg b.i.d. or Sac/val  100 mg  200 mg b.i.d. as per label and at investigator discretion OMT continued throughout the study (excluding ACEi/ARB) Any OMT as per treating physician OMT continued throughout the study (excluding ACEi/ARB) Patient stabilized 3 strata OMT but ACEi/ARB naïve pts PRE-discharge initiation POST-discharge initiation 36 h ACEi washout Hospital admission for ADHF ACEi + OMT ARB + OMT RandomizationtoPRE-orPOST-discharge 36 h ACEi washout Open-labelsac/val attolerateddose Discharge Down-titration or temporary discontinuation of sac/val is allowed in all groups at any time max. 2 weeks Any OMT as per treating physician Pascual-Figal, et al. ESC Heart Failure (Epub ahead of print)
  12. 12. Clinicaltrials.gov identifier: NCT02661217. ESC Congress, Munich, 2018. P6531
  13. 13. Characteristics Pre-discharge N= 497 Post- discharge N= 496 Total N= 993 Prior heart failure history – n (%) No 148 (29.8) 138 (27.8) 286 (28.8) Yes 349 (70.2) 358 (72.2) 707 (71.2) First onset (de novo) HF n (%) 148 (29.8) 138 (27.8) 286 (28.8) Prior hospitalisation for HF n (%) 237 (47.7) 248 (50.0) 485 (48.8) Date of HF diagnosis – n (%) >0 to 3 months 23 (6.6) 21 (5.9) 44 (6.2) >3 to 6 months 16 (4.6) 19 (5.3) 35 (5.0) >6 to 12 months 35 (10.0) 32 (8.9) 67 (9.5) >1 to 2 years 37 (10.6) 40 (11.2) 77 (10.9) >2 to 5 years 94 (26.9) 92 (25.7) 186 (26.3) >5 years 144 (41.3) 152 (42.5) 296 (41.9) Clinicaltrials.gov identifier: NCT02661217. ESC Congress, Munich, 2018. P886 Data on-file
  14. 14. TRANSITION patients’ strata Stratification based on use of RAAS medications prior to hospitalization ACEI/ARB -naïve patients defined as either: • without any previous treatment with ACEI or ARBs, or • without ACEI/ARB therapy for at least 4 weeks before hospital admission due to ADHF as reported in IVRS Clinicaltrials.gov identifier: NCT02661217. ESC Congress, Munich, 2018. P886
  15. 15. Primary and secondary endpoints 45 62,5 86,4 4,5 50,4 68 [VALOR] 3,5 0 10 20 30 40 50 60 70 80 90 100 Proportionofpatients(%) Primary endpoint On target dose 200 mg bid of sac/val at Week 10 Achieved and maintained 100 mg and/or 200 mg bid of sac/val or at least 2 weeks leading to Week 10 Achieved and maintained any dose of sac/val for at least 2 weeks leading to Week 10 Permanently discontinued sac/val due to AE RRR 0.89 (0.78, 1.02) P= 0.092 RRR 0.92 (0.84, 1.01) P= 0.071 RRR 0.97 (0.93, 1.02) P= 0.262 RRR 1.29 (0.69, 2.39) P= 0.424 Pre-discharge initiation (N= 493) Post-discharge initiation (N= 490) AE, adverse events; bid, twice daily; sac/val, sacubitril/valsartan; RRR, relative risk ratio * Safetyl analysis set Clinicaltrials.gov identifier: NCT02661217. ESC Congress, Munich, 2018. P886
  16. 16. AEs and treatment interruptions AE, adverse event; SAE, serious adverse event * Fischer’s Exact Test, Full analysis set Pre-discharge N= 497 n (%) Post-discharge N= 496 n (%) P value* Patients with 1 AE, n (%) 338 (68.0) 323 (65.1) 0.335 Patients with 1 SAE, n (%) 94 (18.9) 88 (17.7) 0.682 Deaths, n (%) 13 (2.6) 10 (2.0) 0.674 Temporary treatment interruption, n (%) Due to AEs 70 (14.1) 55 (11.1) 0.180 Due to SAEs 21 (4.2) 8 (3.6) 0.744 Due to non-SAEs 54 (10.9) 42 (8.5) 0.237 Permanent treatment discontinuation, n (%) Due to AEs 22 (4.4) 20 (4.0) 0.875 Due to SAEs 15 (3.0) 13 (2.6) 0.848 Due to non-SAEs 8 (1.6) 7 (1.4) 1.000 Clinicaltrials.gov identifier: NCT02661217. ESC Congress, Munich, 2018. P886
  17. 17. Most common AEs† during 10-week treatment epoch regardless of study drug relationship AE, adverse event * Fischer’s Exact Test, Full analysis set Pre-discharge N= 497 n (%) Post-discharge N= 496 n (%) P value* Hyperkalemia 55 (11.1) 56 (11.3) 0.920 Hypotension 61 (12.3) 45 (9.1) 0.123 Cardiac failure 34 (6.8) 42 (8.5) 0.343 Dizziness 28 (5.6) 21 (4.2) 0.380 Peripheral edema 17 (3.4) 24 (4.8) 0.270 Renal impairment 25 (5.0) 15 (3.0) 0.146 Diarrhea 12 (2.4) 23 (4.6) 0.060 Urinary tract infection 20 (4.0) 15 (3.0) 0.492 † ≥4% of patients in any group Clinicaltrials.gov identifier: NCT02661217. ESC Congress, Munich, 2018. P886
  18. 18. Most common Serious Adverse Events* COPD, chronic obstructive pulmonary disease; SAE, serious adverse event ** Fischer’s Exact Test, Full analysis set Pre-discharge N= 497 n (%) Post-discharge N= 496 n (%) P value** No. of patients with at least one SAE 94 (18.9) 88 (17.7) 0.682 Hyperkalemia 3 (0.6) 2 (0.4) 1.000 Hypotension 4 (0.8) 2 (0.4) 0.687 Atrial fibrillation 3 (0.6) 4 (0.8) 0.726 Cardiac failure (acute/chronic) 35 (7.0) 38 (7.7) 0.717 Ventricular tachycardia 3 (0.6) 0 (0.0) 0.249 Non-cardiac chest pain 0 (0.0) 3 (0.6) 0.124 Pneumonia 4 (0.8) 3 (0.6) 1.000 Respiratory tract infection 0 (0.0) 3 (0.6) 0.124 Acute kidney injury 6 (1.2) 7 (1.4) 0.789 Renal failure 3 (0.6) 1 (0.2) 0.624 Pulmonary edema 3 (0.6) 2 (0.4) 1.000 COPD 0 (0.0) 4 (0.8) 0.062 * ≥0.5% of patients in any group Clinicaltrials.gov identifier: NCT02661217. ESC Congress, Munich, 2018. P886
  19. 19. Predictors for successful sacubitril/valsartan dose up-titration to 200 mg bid AE, adverse event; CI, confidence interval; eGFR, estimated glomerular filtration rate; HF, heart failure; sac/val, sacubitril/valsartan; SBP, systolic blood pressure For the results shown above, only significant (p <0.05) predictors and treatment group (significant or not) are kept in the model Age (<65 years vs. ≥65 years) eGFR at baseline (≥60 mL/min·1.73 m2 vs. <60 mL/min·1.73 m2) SBP at baseline ≥120 mmHg vs. ≥100-120 mmHg Prior HF history (No vs. Yes) Medical history of hypertension (Yes vs. No) Atrial fibrillation at baseline (No vs. Yes) Starting dose of sac/val (100 mg vs. 50 mg) Treatment (post-discharge vs. pre-discharge) 1.42 1.52 1.48 1.59 1.85 1.77 2.41 1.20 (1.05, 1.93) (1.13, 2.03) (1.11, 1.97) (1.15, 2.19) (1.31, 2.63) (1.33, 2.35) (1.57, 3.68) (0.91, 1.58) 0.023 0.005 0.008 0.005 0.001 <0.001 <0.001 0.196 Predictor Odds ratio 95% CI P value 1 2 3 4 Clinicaltrials.gov identifier: NCT02661217. ESC Congress, Munich, 2018. P886
  20. 20. TRANSITION Sac-Val (both initiation and titration) is feasible and safe in the Transition period of a patient hospitalized due to HF Pascual-Figal DA. Eur J Heart Fail. 2017; 19(8): 1.011-1.013 Greene SJ, Mentz RJ, Felker GM. JAMA Cardiol. 2018; 3: 252
  21. 21. Koehler F. Clinicaltrials.gov identifier: NCT01878630. ESC Congress, Munich, 2018
  22. 22. Koehler F. Clinicaltrials.gov identifier: NCT01878630. ESC Congress, Munich, 2018
  23. 23. Características basales de la población Koehler F. Clinicaltrials.gov identifier: NCT01878630. ESC Congress, Munich, 2018
  24. 24. % day lost due to unplanned CV hospitalisations and all-cause death Koehler F. Clinicaltrials.gov identifier: NCT01878630. ESC Congress, Munich, 2018
  25. 25. Koehler F. Clinicaltrials.gov identifier: NCT01878630. ESC Congress, Munich, 2018
  26. 26. % days lost due to unplanned HF hospitalisations Koehler F. Clinicaltrials.gov identifier: NCT01878630. ESC Congress, Munich, 2018
  27. 27. Koehler F. Clinicaltrials.gov identifier: NCT01878630. ESC Congress, Munich, 2018
  28. 28. Clinicaltrials.gov identifier: NCT02992288. ESC Congress, Munich, 2018
  29. 29. Clinicaltrials.gov identifier: NCT02992288. ESC Congress, Munich, 2018
  30. 30. Clinicaltrials.gov identifier: NCT02992288. ESC Congress, Munich, 2018
  31. 31. No efecto comparado con placebo Clinicaltrials.gov identifier: NCT02992288. ESC Congress, Munich, 2018
  32. 32. Microvascular dysfunction in heart failure with preserved ejection fraction (HFpEF) evidence from PROMIS-HFpEF Carolyn SP, et al. ESC Congress, Munich, 2018
  33. 33. Carolyn SP, et al. ESC Congress, Munich, 2018
  34. 34. InterAtrial Shunt Device (IASD®) Feldman T, Shah SJ, et al. Circ Heart Fail. 2016 Jul; 9(7) NCT02600234
  35. 35. Feldman T. ESC Congress, Munich, 2018
  36. 36. Feldman T. ESC Congress, Munich, 2018
  37. 37. Shunt Patency Feldman T. ESC Congress, Munich, 2018
  38. 38. Change in NYHA Functional Class: InterAtrial Shunt Device vs. Sham Control Feldman T, MD. ESC Congress, Munich, 2018
  39. 39. Feldman T. ESC Congress, Munich, 2018
  40. 40. Decreased AF burden with dynamic optimization of CRT pacing using the AdaptivCRT algorithm in Heart Failure patients: Analysis of real-world patient data Figure: Highlight ESC Munich. Aug 29, 2018 Singh J, et al. Eur Heart J. 2018; 39: 482. P2491
  41. 41. Singh J, et al. Eur Heart J. 2018; 39: 482. P2491
  42. 42. Singh J, et al. Eur Heart J. 2018; 39: 482. P2491
  43. 43. Impact of mineralocorticoid receptor antagonists on sudden cardiac death in patients with heart failure and left ventricular systolic dysfunction: a meta-analysis of three randomized controlled trials. X. Rosselló (Palma de Mallorca, ES) • Se presenta un metanálisis de 3 estudios sobre el uso de antagonistas de los receptores de mineralocorticoide (MAR) en pacientes con ICFEr en la incidencia de muerte súbita (MS) con 11.032 pacientes vs. placebo • Estudios RALES, EPHESUS y EMPHASIS-HF • Conclusiones: – Los MAR reducen un 23% el riesgo de MS en pacientes con ICFEr (objetivo 1) – El uso de MAR debería tenerse en cuenta como terapia de primera línea, así como las otras con clara evidencia (BB IECAS) Rosselló X. Eur Heart J. 2018; 39: 17
  44. 44. • Conclusiones: – La terapia guiada de concentración sérica de digoxina se asoció con un aumento de la mortalidad en pacientes con ICFEr con óptimo tratamiento médico – Solo en niveles séricos <0,9 ng/mL no se objetivó un aumento de mortalidad – Se refuerza la opinión de expertos que digoxina debería ser usada cuidadosamente en pacientes seleccionados con niveles controlados The impact of serum concentration guided digoxin therapy on mortality: a long-term follow-up, propensity-matched cohort study. B. Muk (Budapest, HU) Muk B, et al. European Heart Journal, Volume 39, Issue suppl_1, 1 August 2018, ehy564.205, https://doi.org/10.1093/eurheartj/ehy564.205"
  45. 45. Characteristics of heart failure patients treated with Sacubitril-Valsartan in Europe. Results from ARIADNE Zeymer U, et al. Eur Heart J. 2018; 39: 174
  46. 46. Zeymer U, et al. Eur Heart J. 2018; 39: 174
  47. 47. Beware of making dose comparisons for efficacy in post-hoc analyses of achieved dose in up-titrating studies: lessons from the EMPHASIS trial Ferreira JP, et al. Eur Heart J. 2018; 174(39): 910
  48. 48. Tolerability and safety of sacubitril/valsartan in high-risk subgroups Neiva JN, et al. Eur Heart J. 2018; 174-175(39): 911
  49. 49. Treatment with insulin is associated with worse outcome in patients with chronic heart failure and diabetes Cosmi D, et al. Eur Heart J. 2018; 39: 680
  50. 50. Cosmi D, et al. Eur Heart J. 2018; 39: 680
  51. 51. Cosmi D, et al. Eur Heart J. 2018; 39: 680
  52. 52. – Independiente de la adherencia del médico a las guías clínicas, la adherencia del paciente jugó un rol clave en pacientes con IC, en cuanto a la mortalidad y las rehospitalizaciones por IC Physician and patient adherence to guidelines is associated with better prognosis in patients with heart failure: insights from the Optimize Heart Failure Care Program. Y. M. Lopatin (Volgograd, RU) Lopatin YM, et al. Eur Heart J. 2018; 39: 19
  53. 53. The role of statins in patients with heart failure with preserved, mid-range, and reduced ejection fraction. A meta-analysis and systematic review Science and Fiction in heart failure
  54. 54. Fourth Universal Definition of Myocardial Infarction (2018). J Am Coll Cardiol. 2018; 25 [Epub ahead of print]
  55. 55.  IC asociada a envejecimiento y comorbilidad, precisa esfuerzo organizativo  Sacubitrilo-valsartán presenta buena tolerancia y es factible en el periodo vulnerable tras una hospitalización por IC  Datos favorables de telemedicina posthospitalización, 24 h/7días y sin depresión.  TRC adaptada puede prevenir FA  ICFE preservada: disfunción microvascular y shunt interatrial  Fármacos con evidencia deben ser usados y optimizados en la vida real de forma adecuada Mensajes finales

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