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ICFEr. Sacubitrilo/valsartán

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Ponencia presentada por el Dr. Nicolás Manito Lorite en el directo online ‘Fármacos que mejoran el pronóstico cardiovascular’, realizado en la Casa del Corazón el 5 de junio de 2018

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ICFEr. Sacubitrilo/valsartán

  1. 1. Fármacos que mejoran el pronóstico cardiovascular Fármacos que mejoran el pronóstico cardiovascular: Sacubitrilo/Valsartan Dr. Nicolás Manito Jefe Clínico de la Unidad de Insuficiencia Cardíaca Avanzada y Trasplante Cardíaco Hospital Universitario de Bellvitge Hospitalet del Llobregat – Barcelona WEBINAR 5 DE JUNIO 2018
  2. 2. Fármacos que mejoran el pronóstico cardiovascular Vasorelaxation  Blood pressure  Sympathetic tone  Aldosterone levels  Fibrosis  Hypertrophy  Natriuresis/diuresis Inactive fragments Natriuretic and other vasoactive peptides* AT1 Receptor Vasoconstriction  Blood pressure  Sympathetic tone  Aldosterone  Fibrosis  Hypertrophy Angiotensinogen (liver secretion) Ang I Ang II RAAS – – *Neprilysin substrates listed in order of relative affinity for NEP: ANP, CNP, Ang II, Ang I, adrenomedullin, substance P, bradykinin, endothelin-1, BNP Levin et al. N Engl J Med 1998;339:321–8; Nathisuwan & Talbert. Pharmacotherapy 2002;22:27–42; Schrier & Abraham N Engl J Med 2009;341:577–85; Langenickel & Dole. Drug Discov Today: Ther Strateg 2012;9:e131–9; Feng et al. Tetrahedron Letters 2012;53:275–6 LCZ696 Sacubitril (AHU377; pro-drug) Inhibiting Enhancing LBQ657 (NEP inhibitor) OH O HN O HO O Valsartan N NHN N N O OH O LCZ696 simultaneously inhibits NEP (via LBQ657) and blocks the AT1 receptor (via valsartan)
  3. 3. Fármacos que mejoran el pronóstico cardiovascular 0 16 32 40 24 8 Enalapril (n=4212) 360 720 10800 180 540 900 1260 Days After Randomization 4187 4212 3922 3883 3663 3579 3018 2922 2257 2123 1544 1488 896 853 249 236 LCZ696 Enalapril Patients at Risk 1117 (26.5%) Kaplan-MeierEstimateof CumulativeRates(%) 914 (21.8%) LCZ696 (n=4187) HR = 0.80 (0.73-0.87) P = 0.0000004 Number needed to treat = 21 PARADIGM-HF: CV Death or HF Hospitalization (Primary Endpoint) McMurray et al. NEJM 2014 15% at 1 yr
  4. 4. Fármacos que mejoran el pronóstico cardiovascular PARADIGM-HF CAUSES / MODE OF DEATH Desai AS et al. Eur Heart J 2015;36:1990–97
  5. 5. Fármacos que mejoran el pronóstico cardiovascular Among a total of 1195 patients with at least one HF hospitalization, 410 (34%) had at least one further HF hospitalization. Sacubitril/valsartan compared with enalapril reduced the risk of recurrent HF hospitalization using the negative binomial model [rate ratio (RR) 0.77, 95% confidence interval (CI) 0.67–0.89], the WLW method [hazard ratio (HR) 0.79, 95% CI 0.71–0.89], the LWYY method (RR 0.78, 95% CI 0.68–0.90), and the joint frailty model (HR 0.75, 95% CI 0.66– 0.86) (all P<0.001)
  6. 6. Fármacos que mejoran el pronóstico cardiovascular Autor/Centro Hosp. Pacientes (n) Seguimiento medio (mes) FEVI media pre S/V FEVI media pos S/V P 1. Martinez-Selles M 427 7 28,7 32,3 < 0,001 H.U.Greg. Mar. Madrid 2. Torres F 61 3 34,3 38 < 0,01 H. Costa del Sol. Marbella 3. Maurin V 80 3 28,4 31,9 < 0,001 H. U. Burdeos. Francia 4. De Diego C 120 9 30,4 35,1 < 0,01 H.U. Torrevieja. Alicante 5. Nazzari H 43 6 27,4 36,4 < 0,001 U. British C.Vancouver 6. Pandey AK 60 12 27,3 37,5 < 0,001 U.Cambridge.Ontario 7. Almufleh A 48 3 25,3 30,14 < 0,001 U. Otawa 8. Martins P. 125 4 29,6 34,8 < 0,001 Ziekenhuis Oost-Limburg 9. Kalantari S. U. Chicago 40 3 32,0 35,0 < 0,01 N / Media FEVI 1.004 5,5 29,3 34,6 +5,3% SACUBITRIL/VALSARTAN (S/V) EN PRACTICA CLINICA REAL
  7. 7. Fármacos que mejoran el pronóstico cardiovascular
  8. 8. Fármacos que mejoran el pronóstico cardiovascular - eGFR: was available for all patients. - Urinary albumin/creatinine ratio (UACR) n =1872 PARADIGM-HF CKD: 2,745 patients (33%). 24% had an increased UACR S/V vs Enal : - 1.61 ml/min/1.73 m2/year; [95% CI: -1.77 to -1.44 ml/min/1.73 m2/year] vs. - 2.04 ml/min/1.73 m2/year [95% CI: 2.21 to 1.88 ml/min/1.73 m2/year ]; p < 0.001)
  9. 9. Fármacos que mejoran el pronóstico cardiovascular Seferovic JP, et al. Lancet Diabetes Endocrinol. 2017;5:333-40 Changes in mean HbA1c
  10. 10. Fármacos que mejoran el pronóstico cardiovascular Time to insulin initiation Seferovic JP, et al. Lancet Diabetes Endocrinol. 2017;5:333-40
  11. 11. Fármacos que mejoran el pronóstico cardiovascular Lancet Diabetes Endocrinol 2018 Published Online April 13, 2018 Compared with enalapril, the difference in favour of Sac/Val was 0·6 mL/min per 1·73 m² per year in patients with diabetes compared with 0·3 mL/min per 1·73 m² per year in those without diabetes (treatment-by-diabetes interaction p=0·038
  12. 12. Fármacos que mejoran el pronóstico cardiovascular
  13. 13. Fármacos que mejoran el pronóstico cardiovascular Burnett H et al. Circ Heart Fail. 2017;10:e003529
  14. 14. Fármacos que mejoran el pronóstico cardiovascular Results of random effect network meta-analysis for all-cause mortality: hazard ratios for intervention versus placebo for all-cause mortality and 95% credible intervals. Burnett H et al. Circ Heart Fail. 2017;10:e003529 57 randomized controlled trials
  15. 15. Fármacos que mejoran el pronóstico cardiovascular

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