Effect of vericiguat on left ventricular structure and function in patients with heart failure with reduced ejection fraction: The VICTORIA echocardiographic substudy
Language English Country England, Great Britain Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
36994634
DOI
10.1002/ejhf.2836
Knihovny.cz E-resources
- Keywords
- Echocardiography, Heart failure with reduced ejection fraction, Left ventricular function, Left ventricular structure, Vericiguat,
- MeSH
- Echocardiography MeSH
- Ventricular Function, Left MeSH
- Heterocyclic Compounds, 2-Ring * MeSH
- Humans MeSH
- Heart Failure * diagnostic imaging drug therapy chemically induced MeSH
- Stroke Volume MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Heterocyclic Compounds, 2-Ring * MeSH
- vericiguat MeSH Browser
AIM: Vericiguat significantly reduced the primary composite outcome of heart failure (HF) hospitalization or cardiovascular death in the VICTORIA trial. It is unknown if these outcome benefits are related to reverse left ventricular (LV) remodelling with vericiguat in patients with HF with reduced ejection fraction (HFrEF). The aim of this study was to compare the effects of vericiguat versus placebo on LV structure and function after 8 months of therapy in patients with HFrEF. METHODS AND RESULTS: Standardized transthoracic echocardiography (TTE) was performed at baseline and after 8 months of therapy in a subset of HFrEF patients in VICTORIA. The co-primary endpoints were changes in LV end-systolic volume index (LVESVI) and LV ejection fraction (LVEF). Quality assurance and central reading were performed by an echocardiographic core laboratory blinded to treatment assignment. A total of 419 patients (208 vericiguat, 211 placebo) with high-quality paired TTE at baseline and 8 months were included. Baseline clinical characteristics were well balanced between treatment groups and echocardiographic characteristics were representative of patients with HFrEF. LVESVI significantly declined (60.7 ± 26.8 to 56.8 ± 30.4 ml/m2 ; p < 0.01) and LVEF significantly increased (33.0 ± 9.4% to 36.1 ± 10.2%; p < 0.01) in the vericiguat group, but similarly in the placebo group (absolute changes for vericiguat vs. placebo: LVESVI -3.8 ± 15.4 vs. -7.1 ± 20.5 ml/m2 ; p = 0.07 and LVEF +3.2 ± 8.0% vs. +2.4 ± 7.6%; p = 0.31). The absolute rate per 100 patient-years of the primary composite endpoint at 8 months tended to be lower in the vericiguat group (19.8) than the placebo group (29.6) (p = 0.07). CONCLUSIONS: In this pre-specified echocardiographic study, significant improvements in LV structure and function occurred over 8 months in both vericiguat and placebo in a high-risk HFrEF population with recent worsening HF. Further studies are warranted to define the mechanisms of vericiguat's benefit in HFrEF.
Canadian VIGOUR Centre University of Alberta Edmonton AB Canada
Cape Heart Institute University of Cape Town Cape Town South Africa
Charité University Medicine German Heart Center Berlin Germany
Department of Cardiology Institute for Clinical and Experimental Medicine Prague Czech Republic
INECO Neurociencias Oroño Fundación INECO Rosario Argentina
Inova Heart and Vascular Institute Falls Church VA USA
Merck and Co Inc Rahway NJ USA
National Heart Centre Singapore and Duke National University of Singapore Singapore Singapore
Unidad de Cirugía Cardiovascular de Guatemala Guatemala City Guatemala
Volgograd State Medical University Volgograd Regional Cardiology Center Volgograd Russian Federation
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Ponikowski P, Voors AA, Anker SD, Bueno H, Cleland JGF, Coats AJS, et al.; ESC Scientific Document Group. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: the Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur Heart J. 2016;37:2129-200.
Butler J, Djatche LM, Sawhney B, Chakladar S, Yang L, Brady JE, et al. Clinical and economic burden of chronic heart failure and reduced ejection fraction following a worsening heart failure event. Adv Ther. 2020;37:4015-32.
Hamo CE, Fonarow GC, Greene SJ, Vaduganathan M, Yancy CW, Heidenreich P, et al. Temporal trends in risk profiles among patients hospitalized for heart failure. Am Heart J. 2020;29:154-63.
Greene SJ, Gheorghiade M, Borlaug BA, Pieske B, Vaduganathan M, Burnett JC Jr, et al. The cGMP signaling pathway as a therapeutic target in heart failure with preserved ejection fraction. J Am Heart Assoc. 2013;2:e000536.
Follmann M, Ackerstaff J, Redlich G, Wunder F, Lang D, Kern A, et al. Discovery of the soluble guanylate cyclase stimulator vericiguat (BAY 1021189) for the treatment of chronic heart failure. J Med Chem. 2017;60:5146-61.
Gheorghiade M, Greene SJ, Butler J, Filippatos G, Lam CS, Maggioni AP, et al.; SOCRATES-REDUCED Investigators and Coordinators. 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 trial. JAMA. 2015;314:2251-62.
Armstrong PW, Pieske B, Anstrom KJ, Ezekowitz J, Hernandez AF, Butler J, et al.; VICTORIA Study Group. Vericiguat in patients with heart failure and reduced ejection fraction. N Engl J Med. 2020;382:1883-93.
Butler J, Anstrom KJ, Armstrong PW. Comparing the benefit of novel therapies across clinical trials: insights from the VICTORIA trial. Circulation. 2020;142:717-9.
Gheorghiade M, Marti CN, Sabbah HN, Roessig L, Greene SJ, Bohm M, et al. Soluble guanylate cyclase: a potential therapeutic target for heart failure. Heart Fail Rev. 2013;18:123-34.
Sandner P. From molecules to patients: exploring the therapeutic role of soluble guanylate cyclase stimulators. Biol Chem. 2018;399:679-90.
Kolijn D, Kovács Á, Herwig M, Lódi M, Sieme M, Alhaj A, et al. Enhanced cardiomyocyte function in hypertensive rats with diastolic dysfunction and human heart failure patients after acute treatment with soluble guanylyl cyclase (sGC) activator. Front Physiol. 2020;25:345.
Armstrong PW, Armstrong PW, Roessig L, Patel MJ, Anstrom KJ, Butler J, et al. A multicenter, randomized, double-blind, placebo-controlled trial of the efficacy and safety of the oral soluble guanylate cyclase stimulator: the VICTORIA trial. JACC Heart Fail. 2018;6:96-104.
Pieske B, Patel MJ, Westerhout CM, Anstrom KJ, Butler J, Ezekowtiz J, et al.; VICTORIA Study Group. Baseline features of the VICTORIA (Vericiguat Global Study in Subjects with Heart Failure with Reduced Ejection Fraction) trial. Eur J Heart Fail. 2019;21:1596-604.
Lang RM, Badano LP, Mor-Avi V, Afilalo J, Armstrong A, Ernande L, et al. Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. Eur Heart J Cardiovasc Imaging. 2015;16:233-70.
Nagueh SF, Smiseth OA, Appleton CP, Byrd BF 3rd, Dokainish H, Edvardsen T, et al. Recommendations for the evaluation of left ventricular diastolic function by echocardiography: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. Eur Heart J Cardiovasc Imaging. 2016;17:1321-60.
Tardif JC, O'Meara E, Komajda M, Böhm M, Borer JS, Ford I, et al.; SHIFT Investigators. Effects of selective heart rate reduction with ivabradine on left ventricular remodelling and function: results from the SHIFT echocardiography substudy. Eur Heart J. 2011;32:2507-15.
Bonderman D, Ghio S, Felix SB, Ghofrani HA, Michelakis E, Mitrovic V, et al.; Left Ventricular Systolic Dysfunction Associated With Pulmonary Hypertension Riociguat Trial (LEPHT) Study Group. Riociguat for patients with pulmonary hypertension caused by systolic left ventricular dysfunction: a phase IIb double-blind, randomized, placebo-controlled, dose-ranging hemodynamic study. Circulation. 2013;128:502-11.
Omar M, Jensen J, Ali M, Frederiksen PH, Kistorp C, Videbaek L, et al. Associations of empagliflozin with left ventricular volumes, mass, and function in patients with heart failure and reduced ejection fraction: a substudy of the Empire HF randomized clinical trial. JAMA Cardiol. 2021;6:836-40.
McMurray JJV, Ponikowski P, Bolli GB, Lukashevich V, Kozlovski P, Kothny W, et al.; VIVIDD Trial Committees and Investigators. Effects of vildagliptin on ventricular function in patients with type 2 diabetes mellitus and heart failure: a randomized placebo-controlled trial. JACC Heart Fail. 2018;6:8-17.
Jorsal A, Kistorp C, Holmager P, Tougaard RS, Nielsen R, Hänselmann A, et al. Effect of liraglutide, a glucagon-like peptide-1 analogue, on left ventricular function in stable chronic heart failure patients with and without diabetes (LIVE) - a multicentre, double-blind, randomised, placebo-controlled trial. Eur J Heart Fail. 2017;19:69-77.
Dargie HJ, Hildebrandt PR, Riegger GA, JJ MM, SO MM, Roberts JN, et al. A randomized, placebo-controlled trial assessing the effects of rosiglitazone on echocardiographic function and cardiac status in type 2 diabetic patients with New York Heart Association Functional class I or II heart failure. J Am Coll Cardiol. 2007;49:1696-704.
Doughty RN, Whalley GA, Walsh HA, Gamble GD, López-Sendón J, Sharpe N; CAPRICORN Echo Substudy Investigators. Effects of carvedilol on left ventricular remodeling after acute myocardial infarction: the CAPRICORN Echo Substudy. Circulation. 2004;109:201-6.
Wong M, Staszewsky L, Latini R, Barlera S, Volpi A, Chiang YT, et al.; Val-HeFT Heart Failure Trial Investigators. Valsartan benefits left ventricular structure and function in heart failure: Val-HeFT echocardiographic study. J Am Coll Cardiol. 2002;40:970-5.
Wong M, Germanson T, Taylor WR, Cohen IS, Perry G, Baruch L, et al. Felodipine improves left ventricular emptying in patients with chronic heart failure: V-HeFT III echocardiographic substudy of multicenter reproducibility and detecting functional change. J Card Fail. 2000;6:19-28.
