The future landscape for Heart Failure Adriaan Voors, UMCG - - PowerPoint PPT Presentation

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The future landscape for Heart Failure Adriaan Voors, UMCG - - PowerPoint PPT Presentation

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WCN 2020 The future landscape for Heart Failure Adriaan Voors, UMCG University Medical Center Groningen WCN 2020 Disclosures AAV received consultancy fees and/or research grants from: Amgen, AstraZeneca, Bayer AG, Boehringer Ingelheim,

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University Medical Center Groningen

WCN 2020

The future landscape for Heart Failure

Adriaan Voors, UMCG

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University Medical Center Groningen

WCN 2020

Disclosures

  • AAV received consultancy fees and/or research grants from: Amgen,

AstraZeneca, Bayer AG, Boehringer Ingelheim, Cytokinetics, Merck, Myokardia, Novartis, Roche Diagnostics

  • AAV is supported by a grant from the European Commission: FP7-242209-

BIOSTAT-CHF

  • AAV is Clinical Established Investigator and supported by other grants of

the Dutch Heart Foundation

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University Medical Center Groningen

WCN 2020

  • Bad for Pandemic:

COVID-19

  • Good for Pandemic:

Heart Failure

2020

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University Medical Center Groningen

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University Medical Center Groningen

CONSENSUS RALES COPERNICUS DAPA-HF PARADIGM-HF + CRT-P/D

Treatment of HFrEF 1987-2019: what have we achieved?

Adapted from: McMurray JJV, Eur J Heart Fail 2011

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University Medical Center Groningen

WCN 2020

Increase in co-morbidities in HF from 2002-2014

Conrad et al. Lancet 2018

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University Medical Center Groningen

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University Medical Center Groningen

In patients receiving dapagliflozin on top of SoC; CV-death or HFH still occurred at a rate of 11.6 events per 100 patient years (DAPA-HF 2019) In patients receiving empagliflozin on top of SoC; CV-death or HFH still occurred at a rate of 14.6 events per 100 patient years (EMPEROR-reduced 2020)

Residual risk in 2020

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WCN 2020

University Medical Center Groningen

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University Medical Center Groningen

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Armstrong et al. JACC-HF 2017

Vericiguat increases sensitivy to NO and directly stimulates sGC leading to improved myocardial and vascular function

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University Medical Center Groningen

WCN 2020

VICTORIA: design

  • 5050 patients with HF, NYHA II-IV and LVEF <45%
  • High risk patients with recent HFH or IV diuretic use
  • Elevated natriuretic peptides (BNP or NT-proBNP)
  • Primary Endpoint: composite of death from cardiovascular

causes or first hospitalization for heart failure

Armstrong et al. New Engl J Med 2020

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University Medical Center Groningen

WCN 2020

Primary Endpoint CV Death or HFH

HR 0.90 (95% CI 0.82–0.98) P-value 0.019

Armstrong et al. New Engl J Med 2020

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University Medical Center Groningen

WCN 2020

Safety

Vericiguat Placebo Difference in % vs. Placebo No. (%) No. (%) Estimate (95% CI)* P-value Patients in population 2519 2515 Symptomatic hypotension 229 (9.1) 198 (7.9) 1.2 (-0.3 to 2.8) 0.121 Syncope 101 (4.0) 87 (3.5) 0.6 (-0.5 to 1.6) 0.303

▪ Serious adverse events similar: vericiguat (32.8%), placebo (34.8%) ▪ No adverse effect on blood pressure ▪ No adverse effects on potassium ▪ No adverse effect on renal function

Armstrong et al. New Engl J Med 2020

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University Medical Center Groningen

WCN 2020

  • Bad for Pandemic:

COVID-19

  • Good for Pandemic:

Heart Failure

2020

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University Medical Center Groningen

WCN 2020 WCN 2020

University Medical Center Groningen

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University Medical Center Groningen

WCN 2020

  • Omecamtiv mecarbil, a novel

myotrope, increases the number of myosin/actin connections

  • Increases duration of systole
  • Increases stroke volume
  • No increase in myocyte Calcium
  • No change in MVO2

Omecamtiv Mecarbil: mode of action

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University Medical Center Groningen

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University Medical Center Groningen

  • 8256 patients with HFrEF (LVEF ≤ 35%)
  • NYHA II-IV and elevated (NT-pro)BNP
  • Currently hospitalized for HF or <1 year HF

hospitalization/ urgent HF visit

  • Primary endpoint; CV death, HF hospitalization, urgent HF

visit

GALACTIC-HF: design

Teerlink et al. NEJM 2020

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University Medical Center Groningen

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University Medical Center Groningen

GALACTIC-HF: primary outcome

Teerlink et al. NEJM 2020

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University Medical Center Groningen

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University Medical Center Groningen

GALACTIC-HF: subgroup analyses

Teerlink et al. NEJM 2020

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University Medical Center Groningen

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University Medical Center Groningen

  • No differences between omecamtiv and placebo on Serious

Adverse Events

  • No effects on systolic blood pressure
  • No effects on renal function
  • Reduction in heart rate
  • Decrease in NT-proBNP
  • Increase in Troponin

GALACTIC-HF: Safety

Teerlink et al. NEJM 2020

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University Medical Center Groningen

WCN 2020

  • Bad for Pandemic:

COVID-19

  • Good for Pandemic:

Heart Failure

2020

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University Medical Center Groningen

WCN 2020

AFFIRM-AHF

Lancet Nov 2020

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University Medical Center Groningen

2016 ESC HF Guidelines

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University Medical Center Groningen

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University Medical Center Groningen

  • 1132 patients with iron deficiency, hospitalized for acute heart

failure

  • LVEF < 50%
  • Before discharge randomized to intravenous ferric

carboxymaltose or placebo for up to 24 weeks

  • Primary outcome: composite of total hospitalisations for heart

failure and cardiovascular death to week 52

AFFIRM-AHF

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University Medical Center Groningen

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University Medical Center Groningen

AFFIRM-AHF: primary outcome

Ponikowski et al. Lancet 2020

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University Medical Center Groningen

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University Medical Center Groningen

Treatment of HFrEF: many choices

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University Medical Center Groningen

WCN 2020

Comparison of Novel HFrEF Trials: Relative versus Absolute Risk Reduction

10 20 30 40 50 60 70 80 PARADIGM DAPA VICTORIA GALACTIC AFFIRM Placebo Active

RRR -8% ARR -2.1% RRR -20% ARR -2.7% RRR -26% ARR -4.0% RRR -10% ARR -4.2%

*CV death and/or HFH **CV death/HFH/UHFV *** CV death/total HFH * * ** **

RRR= relative risk reduction; ARR = absolute risk reduction CV = cardiovascularl HFH = heart failure hospitalization UHFV = urgent heart failure visit

RRR -21% ARR -15%

***

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University Medical Center Groningen

WCN 2020

By courtesy of Kevin Damman

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University Medical Center Groningen

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University Medical Center Groningen

2016 ESC HF Guidelines

2021?

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University Medical Center Groningen

WCN 2020 Foundational Therapies Consider Add-on Therapy:

diuretics Ivabradine vericiguat

  • mcamtiv

i.v. iron digoxin Nitrates/ hydralazine

ACE/ARB/ARNI Beta-blocker MRA SGTL2-i

HFrEF Treatment