New Pharmacotherapy for the Treatment of Heart Failure

New Pharmacotherapy for the Treatment of Heart Failure Samer S. Najjar, MD Professor of Medicine, Georgetown University Medical Director, Advanced Heart Failure Program Med. Star Washington Hospital Center

Financial Disclosure Samer Najjar, MD Research Support Medtronic

Outline • FDA approved pharmacotherapy • Experimental pharmacotherapy

Guideline Directed Medical Therapy HFr. EF Therapy Diuretics Digoxin ACE inhibitors ARBs Beta blockers Aldactone/Eplerenone Hydralazine/nitrates ICD CRT Class III Class IV Adapted from Almeda FQ, Hollenberg SM. Postgrad Med. 2003; 113: 41

Angiotensin-Neprilysin Inhibition (ARNI) Death from CV causes or Hosp for HF Swedberg Nat. Rev. Cardiol. 2015; 12: 73 -75

ARNI vs. Enalapril in HF PARADIGM-HF Death from CV causes or Hosp for HF Entresto Mc. Murray JJ et al. N Engl J Med 2014; 371: 993 -1004

ARNI vs. Enalapril in HF PARADIGM-HF Mc. Murray JJ et al. N Engl J Med 2014; 371: 993 -1004

PARADIGM-HF Mc. Murray JJV et al. N Engl J Med 2014; 371: 993 -1004

CV Death or Hospital Readmission for HF 40 Placebo Cumulative frequency (%) 30 18% HR = 0. 82 (0. 75– 0. 90) P < 0. 0001 Ivabradine 20 10 0 0 6 12 18 Swedberg K, et al. Lancet. 2010; 376(9744): 875 -885 24 30

Investigational Interventions • • Medications with known mechanisms of action Medications with novel mechanisms of action Anti-inflammatory medications Biological therapeutics – Cell based – Gene based

Coenzyme Q 10 Lei and Liu, BMC Cardiovascular Disorders (2017) 17: 196

Sodium-glucose cotransporter 2 (SGLT 2) Inhibitor (Gliflozins)

Sodium-glucose cotransporter 2 (SGLT 2) Inhibitor (Gliflozins) Palazzuoli Heart Failure Reviews 2018

Sodium-glucose cotransporter 2 (SGLT 2) Inhibitor EMPA-REG OUTCOME Zinman B et al. N Engl J Med 2015; 373: 2117 -2128.

REDHART Trial Effects of treatment on survival free of hospital readmission for heart failure (HF). Log rank p=0. 10 Van Tassell et al. Circ Heart Fail. 2017; 10: e 004373

Heart Failure with preserved Ejection Fraction (HFp. EF) • PARAGON • EMPEROR HF-Preserved • D-HART 2

Biological Therapeutics in Heart Failure STEM CELLS 2017; 35(5): 1131 -1140

Ongoing Clinical Investigations • • • Ularitide Cenderitide Omecamtiv mecarbil Neuregulin-1 Perhexilin • • • Sildenafil Riociguat Sitaxentan Bendavia Finerenone

Biased Ligand of AT 1 R (TRV 027) - BLAST-AHF Felker et al. J Am Coll Cardiol HF 2015; 3: 193– 201

From: Biased ligand of the angiotensin II type 1 receptor in patients with acute heart failure: a randomized, double-blind, placebo-controlled, phase IIB, dose ranging trial (BLAST-AHF) Eur Heart J. 2017; 38(30): 2364 -2373. doi: 10. 1093/eurheartj/ehx 196 Eur Heart J | Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals. permissions@oup. com.

FINERENONE ARTS-HF Filippatos et al. European Heart Journal (2016) 37, 2105– 2114

Kaplan–Meier Estimates of the Probability of Freedom from Death from Cardiovascular Causes. Packer M et al. N Engl J Med 2017; 376: 1956 -1964.

Treatment of HFr. EF Stage C and D Yancy et al. J Am Coll Cardiol 2017; Apr 28: [Epub ahead of print]

From: Effect of Vericiguat, a Soluble Guanylate Cyclase Stimulator, on Natriuretic Peptide Levels in Patients With Worsening Chronic Heart Failure and Reduced Ejection Fraction. The SOCRATES-REDUCED Randomized JAMA. Trial 2015; 314(21): 2251 -2262. doi: 10. 1001/jama. 2015. 15734 Figure Legend: Time to Composite of Cardiovascular Death or Heart Failure Hospitalization. CV indicates cardiovascular; HF, heart failure. Hazard ratios for vericiguat/placebo for each group were as follows: 1. 25 -mg vericiguat group, 0. 97 (95% CI, 0. 50 -1. 88) Copyright © 2015 American Medical Association. 2. 5 -mg group, 1. 01 (95% CI, 0. 52 -1. 94) Date of download: 3/5/2018 All rights reserved.