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, 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 University Medical Center Groningen
WCN 2020 2020 • Bad for Pandemic: • Good for Pandemic: Heart Failure COVID-19 University Medical Center Groningen
WCN 2020 WCN 2020 Treatment of HFrEF 1987-2019: what have we achieved? CONSENSUS RALES + CRT-P/D DAPA-HF COPERNICUS PARADIGM-HF Adapted from: McMurray JJV, Eur J Heart Fail 2011 University Medical Center Groningen University Medical Center Groningen
WCN 2020 Increase in co-morbidities in HF from 2002-2014 Conrad et al. Lancet 2018 University Medical Center Groningen
WCN 2020 WCN 2020 Residual risk in 2020 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) University Medical Center Groningen University Medical Center Groningen
WCN 2020 University Medical Center Groningen
WCN 2020 Vericiguat increases sensitivy to NO and directly stimulates sGC leading to improved myocardial and vascular function Armstrong et al. JACC-HF 2017 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 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 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 University Medical Center Groningen
WCN 2020 2020 • Bad for Pandemic: • Good for Pandemic: Heart Failure COVID-19 University Medical Center Groningen
WCN 2020 WCN 2020 University Medical Center Groningen University Medical Center Groningen
WCN 2020 Omecamtiv Mecarbil: mode of action • 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 MVO 2 University Medical Center Groningen
WCN 2020 WCN 2020 GALACTIC-HF: design • 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 Teerlink et al. NEJM 2020 University Medical Center Groningen University Medical Center Groningen
WCN 2020 WCN 2020 GALACTIC-HF: primary outcome Teerlink et al. NEJM 2020 University Medical Center Groningen University Medical Center Groningen
WCN 2020 WCN 2020 GALACTIC-HF: subgroup analyses Teerlink et al. NEJM 2020 University Medical Center Groningen University Medical Center Groningen
WCN 2020 WCN 2020 GALACTIC-HF: Safety • 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 Teerlink et al. NEJM 2020 University Medical Center Groningen University Medical Center Groningen
WCN 2020 2020 • Bad for Pandemic: • Good for Pandemic: Heart Failure COVID-19 University Medical Center Groningen
WCN 2020 AFFIRM-AHF Lancet Nov 2020 University Medical Center Groningen
WCN 2020 2016 ESC HF Guidelines University Medical Center Groningen
WCN 2020 WCN 2020 AFFIRM-AHF • 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 University Medical Center Groningen University Medical Center Groningen
WCN 2020 WCN 2020 AFFIRM-AHF: primary outcome Ponikowski et al. Lancet 2020 University Medical Center Groningen University Medical Center Groningen
WCN 2020 WCN 2020 Treatment of HFrEF: many choices University Medical Center Groningen University Medical Center Groningen
WCN 2020 Comparison of Novel HFrEF Trials: Relative versus Absolute Risk Reduction RRR -21% *CV death and/or HFH 80 ARR -15% **CV death/HFH/UHFV 70 *** CV death/total HFH 60 RRR -10% 50 ARR -4.2% Placebo RRR -8% 40 ARR -2.1% RRR -26% Active 30 RRR -20% ARR -4.0% ARR -2.7% 20 10 0 * ** * ** *** PARADIGM DAPA VICTORIA GALACTIC AFFIRM RRR= relative risk reduction; ARR = absolute risk reduction CV = cardiovascularl HFH = heart failure hospitalization UHFV = urgent heart failure visit University Medical Center Groningen
WCN 2020 By courtesy of Kevin Damman University Medical Center Groningen
WCN 2020 WCN 2020 2016 ESC HF Guidelines 2021? University Medical Center Groningen University Medical Center Groningen
WCN 2020 HFrEF Treatment Foundational Therapies ACE/ARB/ARNI Beta-blocker SGTL2-i MRA Consider Add-on Therapy: Nitrates/ diuretics Ivabradine vericiguat omcamtiv i.v. iron digoxin hydralazine University Medical Center Groningen
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