New Pharmacotherapy for the Treatment of Heart Failure

Financial Disclosure Samer S. Najjar, MD Research Support Medtronic Abbott

Guideline Directed Medical Therapy HFr. EF Therapy Diuretics Digoxin ACE inhibitors ARBs Beta blockers

Angiotensin-Neprilysin Inhibition (ARNI) Death from CV causes or Hosp for HF Swedberg Nat. Rev.

ARNI vs. Enalapril in HF PARADIGM-HF Death from CV causes or Hosp for HF

ARNI vs. Enalapril in HF PARADIGM-HF Mc. Murray JJ et al. N Engl J

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

PIONEER-HF Velazquez EJ et al. N Engl J Med. 2019; 380(6): 539 -5478

CV Death or Hospital Readmission for HF 40 Placebo Cumulative frequency (%) 30 18%

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

Dapagliflozin and CV Outcomes in Type 2 Diabetes (DECLARE TIMI-58) Wiviott SD et al.

REDHART Trial Log rank p=0. 10 Van Tassell et al. Circ Heart Fail. 2017;

Ongoing Clinical Investigations • • • Omecamtiv mecarbil Ularitide Cenderitide Neuregulin-1 Perhexilin • •

Myocardiocyte Contractile Cycle Kaplinsky, Mallarkey Drugs Context 2018; 7: 212518.

Omecamtiv Mecarbil Activates Cardiac Myosin Kaplinsky, Mallarkey Drugs Context 2018; 7: 212518.

Omecamtiv Mecarbil Aactivates Cardiac Myosin ATOMIC-HF COSMIC-HF GALACTIC-HF Kaplinsky, Mallarkey Drugs Context 2018; 7:

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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 S. Najjar, MD Research Support Medtronic Abbott

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

PIONEER-HF Velazquez EJ et al. N Engl J Med. 2019; 380(6): 539 -5478

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

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.

Dapagliflozin and CV Outcomes in Type 2 Diabetes (DECLARE TIMI-58) Wiviott SD et al. N Engl J Med. 2019; 380(4): 347 -357.

REDHART Trial Log rank p=0. 10 Van Tassell et al. Circ Heart Fail. 2017; 10: e 004373

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

Myocardiocyte Contractile Cycle Kaplinsky, Mallarkey Drugs Context 2018; 7: 212518.

Omecamtiv Mecarbil Activates Cardiac Myosin Kaplinsky, Mallarkey Drugs Context 2018; 7: 212518.

Omecamtiv Mecarbil Aactivates Cardiac Myosin ATOMIC-HF COSMIC-HF GALACTIC-HF Kaplinsky, Mallarkey Drugs Context 2018; 7: 212518.