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Ensayos clínicos en IC preservada: resultados del PARAGON-HF

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Ponencia presentada por el Dr. Josep Comín Colet en el directo ‘IC preservada y resultados del PARAGON-HF’, realizado en la Casa del Corazón el 9 de septiembre de 2019.

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Ensayos clínicos en IC preservada: resultados del PARAGON-HF

  1. 1. Ensayos clínicos en IC preservada: resultados del PARAGON-HF Dr. Josep Comín Colet Ensayos Clínicos en IC Preservada: resultados del PARAGON-HF Dr. Josep Comín Colet. Jefe del Servicio de Cardiologia del Hospital Universitario de Bellvitge, L’ Hospitalet de Llobregat, Barcelona.
  2. 2. Ensayos clínicos en IC preservada: resultados del PARAGON-HF Dr. Josep Comín Colet Up to 2 weeks Valsartan 160 mg b.i.d. Sacubitril/valsartan 200 mg b.i.d. Sac/val 100 mg b.i.d. On top of optimal background medications for comorbidities (excluding ACEIs and ARBs) Valsartan 80 mg b.i.d. Screening Single-blind run-in period Double-blind, long-term follow-up period¥Randomization N=4822 1─4 weeks* 2─4 weeks^ Safety and tolerability check Safety and tolerability check Diseño del Estudio Solomon, SD et al. JACC Heart Fail. 2017;5:471–482
  3. 3. Ensayos clínicos en IC preservada: resultados del PARAGON-HF Dr. Josep Comín Colet Criterios Inclusión & Exclusión Key inclusion criteria: • Age 50 years; LVEF 45% • Symptoms of HF requiring treatment with diuretic(s) for 30 days prior to screening • Current symptomatic HF (NYHA class II−IV) • Structural heart disease within the 6 months prior to screening (LAE and/or LVH) • Patients with at least 1 of the following: – HF hospitalization within 9 months prior to screening and NT-proBNP >200 pg/mL for patients without AF or >600 pg/mL for patients with AF* OR – NT-proBNP >300 pg/mL for patients without AF or >900 pg/mL for patients with AF* Key exclusion criteria: • History of LVEF <40% • MI, CABG or any event within the 6 months prior to screening that could have reduced the LVEF (unless LVEF confirmed as 45%) • Current acute decompensated HF requiring therapy • Requirement for treatment with two or more of the following: ACEI, ARB or renin inhibitor • SBP <110 mmHg OR SBP 180 mmHg at screening^ • Serum potassium >5.2 mmol/L at screening, or >5.4 mmol/L at the end of each run-in period • eGFR <30 mL/min/1.73m2 at screening, OR at the end of each run-in period eGFR <25 mL/min/1.73m2 or eGFR reduction of >35% compared to that at screening Solomon, SD et al. JACC Heart Fail. 2017;5:471–482
  4. 4. Ensayos clínicos en IC preservada: resultados del PARAGON-HF Dr. Josep Comín Colet Primary objective • To evaluate the efficacy of sacubitril/valsartan compared with valsartan in reducing the rate of the composite endpoint of CV death and total (first and recurrent) HF hospitalizations Secondary objectives • To compare the effects of sacubitril/valsartan vs. valsartan on: ➢ improvement in the KCCQ clinical summary score for HF symptoms and physical limitations at 8 months ➢ improvement in NYHA functional classification at 8 months ➢ delay in the time to the first occurrence of a composite renal endpoint* ➢ delay in the time to all-cause mortality Solomon, SD et al. JACC Heart Fail. 2017;5:471–482
  5. 5. Ensayos clínicos en IC preservada: resultados del PARAGON-HF Dr. Josep Comín Colet Disposición de los Pacientes 11302 patients screened at 788 centers in 43 countries 5754 entered valsartan run-in phase 4822 patients randomized to receive sacubitril/valsartan or valsartan Common reasons for screen failure were: • Insufficient NT-proBNP: 61% • Elevated potassium: 10% • eGFR below inclusion cut-off: 6% • Diagnoses other than HFpEF: 6% • Elevated LFTs: 4% Common reasons for run-in failures were: • Predefined safety AEs*: 65% • Subject decision: 15% • Protocol deviation: 12% • Non-compliance: 5% • Death: 2% 5210 entered sacubitril/valsartan run-in phase Solomon, SD et al., Circ Heart Fail. 2018;11:e004962. DOI: 10.1161/CIRCHEARTFAILURE.118.004962
  6. 6. Ensayos clínicos en IC preservada: resultados del PARAGON-HF Dr. Josep Comín Colet Solomon et al. New England Journal of Medicine, September 1, 2019 DOI: 10.1056/NEJMoa1908655
  7. 7. Ensayos clínicos en IC preservada: resultados del PARAGON-HF Dr. Josep Comín Colet Solomon et al. New England Journal of Medicine, September 1, 2019 DOI: 10.1056/NEJMoa1908655
  8. 8. Ensayos clínicos en IC preservada: resultados del PARAGON-HF Dr. Josep Comín Colet Solomon et al. New England Journal of Medicine, September 1, 2019 DOI: 10.1056/NEJMoa1908655 Characteristic Sacubitril/valsartan (n = 2407) Valsartan (n = 2389) Age—yr 72.7 ± 8.3 72.8 ± 8.5 Female sex — no. (%) 1241 (51.6%) 1238 (51.8%) Region — no. (%) North America 288 (12.0%) 271 (11.3%) Latin America 191 (7.9 %) 179 (7.5 %) Western Europe‡ 699 (29.0%) 691 (28.9%) Central Europe 856 (35.6%) 859 (36.0%) Asia–Pacificand Other 373 (15.5%) 389 (16.3%) Systolic blood pressure — mm Hg §. † 130.5 ± 15.6 130.6 ± 15.3 Estimated glomerular filtration rate (eGFR) – ml/min/1.73 m2 63  19 62  19 Ischemic etiology — no. (%) 899 (37.4%) 824 (34.5%)* Left ventricular ejection fraction — % 57.6 ± 7.8 57.5 ± 8.0 Median N-terminal pro–B-type natriuretic peptide (IQR) — pg/ml 904 [475 , 1596] 915 [453 , 1625] NYHA functional class at randomization — no. (%)† I 73 (3.0%) 64 (2.7%) II 1866 (77.5%) 1840 (77.0%) III 458 (19.0%) 474 (19.8%) IV 8 (0.3 %) 11 (0.5 %)
  9. 9. Ensayos clínicos en IC preservada: resultados del PARAGON-HF Dr. Josep Comín Colet Solomon et al. New England Journal of Medicine, September 1, 2019 DOI: 10.1056/NEJMoa1908655 Characteristic Sacubitril/valsartan (n = 2407) Valsartan (n = 2389) Medical history — no. (%) Hypertension 2304 (95.7%) 2280 (95.4%) Diabetes 1046 (43.5%) 1016 (42.5%) Atrial fibrillation 775 (32.2%) 777 (32.5%) Stroke 266 (11.1%) 242 (10.1%) Hospitalization for heart failure 1135 (47.2%) 1171 (49.0%) Myocardial infarction 561 (23.3%) 522 (21.9%) Treatments at Randomization – no.(%) Diuretics† 2268 (94.2%) 2266 (94.9%) ACE inhibitors or Angiotensin Receptor Blockers (at screening) 2074 (86.2%) 2065 (86.4%) Mineralocorticoid Receptor Antagonists† 581 (24.1%) 638 (26.7%) Beta-Blockers† 1897 (78.8%) 1883 (78.8%)
  10. 10. Ensayos clínicos en IC preservada: resultados del PARAGON-HF Dr. Josep Comín Colet Solomon et al. New England Journal of Medicine, September 1, 2019 DOI: 10.1056/NEJMoa1908655
  11. 11. Ensayos clínicos en IC preservada: resultados del PARAGON-HF Dr. Josep Comín Colet Solomon et al. New England Journal of Medicine, September 1, 2019 DOI: 10.1056/NEJMoa1908655
  12. 12. Ensayos clínicos en IC preservada: resultados del PARAGON-HF Dr. Josep Comín Colet Solomon et al. New England Journal of Medicine, September 1, 2019 DOI: 10.1056/NEJMoa1908655
  13. 13. Ensayos clínicos en IC preservada: resultados del PARAGON-HF Dr. Josep Comín Colet Solomon et al. New England Journal of Medicine, September 1, 2019 DOI: 10.1056/NEJMoa1908655
  14. 14. Ensayos clínicos en IC preservada: resultados del PARAGON-HF Dr. Josep Comín Colet Solomon et al. New England Journal of Medicine, September 1, 2019 DOI: 10.1056/NEJMoa1908655
  15. 15. Ensayos clínicos en IC preservada: resultados del PARAGON-HF Dr. Josep Comín Colet Solomon et al. New England Journal of Medicine, September 1, 2019 DOI: 10.1056/NEJMoa1908655
  16. 16. Ensayos clínicos en IC preservada: resultados del PARAGON-HF Dr. Josep Comín Colet Solomon et al. New England Journal of Medicine, September 1, 2019 DOI: 10.1056/NEJMoa1908655
  17. 17. Ensayos clínicos en IC preservada: resultados del PARAGON-HF Dr. Josep Comín Colet Solomon et al. New England Journal of Medicine, September 1, 2019 DOI: 10.1056/NEJMoa1908655
  18. 18. Ensayos clínicos en IC preservada: resultados del PARAGON-HF Dr. Josep Comín Colet Solomon et al. New England Journal of Medicine, September 1, 2019 DOI: 10.1056/NEJMoa1908655
  19. 19. Ensayos clínicos en IC preservada: resultados del PARAGON-HF Dr. Josep Comín Colet Ensayos Clínicos en IC Preservada: resultados del PARAGON-HF Dr. Josep Comín Colet. Jefe del Servicio de Cardiologia del Hospital Universitario de Bellvitge, L’ Hospitalet de Llobregat, Barcelona.

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