{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T22:56:56Z","timestamp":1783465016677,"version":"3.55.0"},"reference-count":67,"publisher":"IMR Press","issue":"4","license":[{"start":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T00:00:00Z","timestamp":1776643200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Rev. Cardiovasc. Med."],"abstract":"<jats:p>Despite advances in guideline-directed medical therapy (GDMT), heart failure with reduced ejection fraction (HFrEF) remains a progressive condition with high morbidity and mortality. Vericiguat, a soluble guanylate cyclase (sGC) stimulator, represents a novel therapeutic class that augments the nitric oxide\u2013sGC\u2013cyclic guanosine monophosphate (cGMP) pathway, which is impaired in HFrEF. The VICTORIA trial demonstrated that vericiguat significantly reduced the composite endpoint of cardiovascular death or heart failure hospitalization (HFH) in high-risk patients following a worsening event. Recent data from the VICTOR trial and subsequent pooled analyses suggest broader applicability, indicating that vericiguat may signal a potential mortality benefit in selected stable, ambulatory HFrEF patients with elevated natriuretic peptides but without recent hospitalization. The safety profile is favorable, with hypotension being the most common adverse event. Overall, vericiguat offers a valuable therapeutic option for a wide spectrum of HFrEF patients. Moreover, the ability of vericiguat to improve outcomes in both post-worsening and selected high-risk stable populations suggests this sGC stimulator may serve as a critical fifth component of GDMT, offering a new avenue for a personalized approach to HFrEF treatment. This review synthesizes key clinical evidence to elucidate the role of vericiguat in modern HFrEF management.<\/jats:p>","DOI":"10.31083\/rcm48373","type":"journal-article","created":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T10:31:56Z","timestamp":1777458716000},"source":"Crossref","is-referenced-by-count":1,"title":["Vericiguat: A New Horizon for Heart Failure Treatment"],"prefix":"10.31083","volume":"27","author":[{"given":"Carla","family":"Carbonaro","sequence":"first","affiliation":[{"name":"Department of Medical Sciences, University of Turin, 10124 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7868-1852","authenticated-orcid":true,"given":"Pier Paolo","family":"Bocchino","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Cardiovascular and Thoracic Department, \u201cCitta della Salute e della Scienza\u201d Hospital, 10126 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleonora","family":"Bertello","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, University of Turin, 10124 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carola","family":"Griffith Brookles","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, University of Turin, 10124 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Filippo","family":"Angelini","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Cardiovascular and Thoracic Department, \u201cCitta della Salute e della Scienza\u201d Hospital, 10126 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guglielmo","family":"Gallone","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, University of Turin, 10124 Turin, Italy"},{"name":"Division of Cardiology, Cardiovascular and Thoracic Department, \u201cCitta della Salute e della Scienza\u201d Hospital, 10126 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Pidello","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Cardiovascular and Thoracic Department, \u201cCitta della Salute e della Scienza\u201d Hospital, 10126 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amedeo","family":"Feneziani","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, University of Turin, 10124 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Raineri","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Cardiovascular and Thoracic Department, \u201cCitta della Salute e della Scienza\u201d Hospital, 10126 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaetano Maria","family":"De Ferrari","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, University of Turin, 10124 Turin, Italy"},{"name":"Division of Cardiology, Cardiovascular and Thoracic Department, \u201cCitta della Salute e della Scienza\u201d Hospital, 10126 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"16242","published-online":{"date-parts":[[2026,4,20]]},"reference":[{"key":"ref1","unstructured":"2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. 2021. Available at: https:\/\/www.escardio.org\/Guidelines\/Clinical-Practice-Guidelines\/Acute-and-Chronic-Heart-Failure (Accessed: 15 November 2025)."},{"key":"ref2","doi-asserted-by":"publisher","unstructured":"Savarese G, Lund LH. Global Public Health Burden of Heart Failure. Cardiac Failure Review. 2017; 3: 7\u201311.","DOI":"10.15420\/cfr.2016:25:2"},{"key":"ref3","doi-asserted-by":"publisher","unstructured":"Conrad N, Judge A, Tran J, Mohseni H, Hedgecott D, Crespillo AP, et al. Temporal trends and patterns in heart failure incidence: a population-based study of 4 million individuals. Lancet (London, England). 2018; 391: 572\u2013580.","DOI":"10.1016\/S0140-6736(17)32520-5"},{"key":"ref4","doi-asserted-by":"publisher","unstructured":"Cohn JN, Ferrari R, Sharpe N. Cardiac remodeling\u2013concepts and clinical implications: a consensus paper from an international forum on cardiac remodeling. Behalf of an International Forum on Cardiac Remodeling. Journal of the American College of Cardiology. 2000; 35: 569\u2013582.","DOI":"10.1016\/s0735-1097(99)00630-0"},{"key":"ref5","doi-asserted-by":"publisher","unstructured":"Trujillo ME, Ayalasomayajula S, Blaustein RO, Gheyas F. Vericiguat, a novel sGC stimulator: Mechanism of action, clinical, and translational science. Clinical and Translational Science. 2023; 16: 2458\u20132466.","DOI":"10.1111\/cts.13677"},{"key":"ref6","doi-asserted-by":"publisher","unstructured":"CONSENSUS Trial Study Group. Effects of enalapril on mortality in severe congestive heart failure. Results of the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS). The New England Journal of Medicine. 1987; 316: 1429\u20131435.","DOI":"10.1056\/NEJM198706043162301"},{"key":"ref7","doi-asserted-by":"publisher","unstructured":"SOLVD Investigators, Yusuf S, Pitt B, Davis CE, Hood WB, Cohn JN. Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure. The New England Journal of Medicine. 1991; 325: 293\u2013302.","DOI":"10.1056\/NEJM199108013250501"},{"key":"ref8","doi-asserted-by":"publisher","unstructured":"Granger CB, McMurray JJV, Yusuf S, Held P, Michelson EL, Olofsson B, et al. Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function intolerant to angiotensin-converting-enzyme inhibitors: the CHARM-Alternative trial. Lancet (London, England). 2003; 362: 772\u2013776.","DOI":"10.1016\/S0140-6736(03)14284-5"},{"key":"ref9","doi-asserted-by":"publisher","unstructured":"McMurray JJV, Packer M, Desai AS, Gong J, Lefkowitz MP, Rizkala AR, et al. Angiotensin-neprilysin inhibition versus enalapril in heart failure. The New England Journal of Medicine. 2014; 371: 993\u20131004.","DOI":"10.1056\/NEJMoa1409077"},{"key":"ref10","doi-asserted-by":"crossref","unstructured":"Effect of metoprolol CR\/XL in chronic heart failure: Metoprolol CR\/XL Randomised Intervention Trial in Congestive Heart Failure (MERIT-HF). Lancet (London, England). 1999; 353: 2001\u20132007.","DOI":"10.1016\/S0140-6736(99)04440-2"},{"key":"ref11","doi-asserted-by":"publisher","unstructured":"Packer M, Fowler MB, Roecker EB, Coats AJS, Katus HA, Krum H, et al. Effect of carvedilol on the morbidity of patients with severe chronic heart failure: results of the carvedilol prospective randomized cumulative survival (COPERNICUS) study. Circulation. 2002; 106: 2194\u20132199.","DOI":"10.1161\/01.cir.0000035653.72855.bf"},{"key":"ref12","doi-asserted-by":"publisher","unstructured":"Pitt B, Zannad F, Remme WJ, Cody R, Castaigne A, Perez A, et al. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. The New England Journal of Medicine. 1999; 341: 709\u2013717.","DOI":"10.1056\/NEJM199909023411001"},{"key":"ref13","doi-asserted-by":"publisher","unstructured":"Zannad F, McMurray JJ, Krum H, van Veldhuisen DJ, Swedberg K, Shi H, et al. Eplerenone in patients with systolic heart failure and mild symptoms. New England Journal of Medicine. 2011; 364: 11\u201321.","DOI":"10.1056\/NEJMoa1009492"},{"key":"ref14","doi-asserted-by":"publisher","unstructured":"Packer M, Anker SD, Butler J, Filippatos G, Pocock SJ, Carson P, et al. Cardiovascular and Renal Outcomes with Empagliflozin in Heart Failure. The New England Journal of Medicine. 2020; 383: 1413\u20131424.","DOI":"10.1056\/NEJMoa2022190"},{"key":"ref15","doi-asserted-by":"publisher","unstructured":"McMurray JJV, Solomon SD, Inzucchi SE, K\u00f8ber L, Kosiborod MN, Martinez FA, et al. Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction. The New England Journal of Medicine. 2019; 381: 1995\u20132008.","DOI":"10.1056\/NEJMoa1911303"},{"key":"ref16","doi-asserted-by":"publisher","unstructured":"Butler J, Yang M, Manzi MA, Hess GP, Patel MJ, Rhodes T, et al. Clinical Course of Patients With Worsening Heart Failure With Reduced Ejection Fraction. Journal of the American College of Cardiology. 2019; 73: 935\u2013944.","DOI":"10.1016\/j.jacc.2018.11.049"},{"key":"ref17","doi-asserted-by":"publisher","unstructured":"Tsai EJ, Kass DA. Cyclic GMP signaling in cardiovascular pathophysiology and therapeutics. Pharmacology & Therapeutics. 2009; 122: 216\u2013238.","DOI":"10.1016\/j.pharmthera.2009.02.009"},{"key":"ref18","doi-asserted-by":"publisher","unstructured":"Kang C, Lamb YN. Vericiguat: A Review in Chronic Heart Failure with Reduced Ejection Fraction. American Journal of Cardiovascular Drugs: Drugs, Devices, and other Interventions. 2022; 22: 451\u2013459.","DOI":"10.1007\/s40256-022-00538-5"},{"key":"ref19","doi-asserted-by":"publisher","unstructured":"Vannuccini F, Campora A, Barilli M, Palazzuoli A. Vericiguat in Heart Failure: Characteristics, Scientific Evidence and Potential Clinical Applications. Biomedicines. 2022; 10: 2471.","DOI":"10.3390\/biomedicines10102471"},{"key":"ref20","doi-asserted-by":"publisher","unstructured":"Kassis-George H, Verlinden NJ, Fu S, Kanwar M. Vericiguat in Heart Failure with a Reduced Ejection Fraction: Patient Selection and Special Considerations. Therapeutics and Clinical Risk Management. 2022; 18: 315\u2013322.","DOI":"10.2147\/TCRM.S357422"},{"key":"ref21","doi-asserted-by":"publisher","unstructured":"Evgenov OV, Pacher P, Schmidt PM, Hask\u00f3 G, Schmidt HHHW, Stasch JP. NO-independent stimulators and activators of soluble guanylate cyclase: discovery and therapeutic potential. Nature Reviews. Drug Discovery. 2006; 5: 755\u2013768.","DOI":"10.1038\/nrd2038"},{"key":"ref22","doi-asserted-by":"publisher","unstructured":"Emdin M, Aimo A, Castiglione V, Vergaro G, Georgiopoulos G, Saccaro LF, et al. Targeting Cyclic Guanosine Monophosphate to Treat Heart Failure: JACC Review Topic of the Week. Journal of the American College of Cardiology. 2020; 76: 1795\u20131807.","DOI":"10.1016\/j.jacc.2020.08.031"},{"key":"ref23","doi-asserted-by":"publisher","unstructured":"Gheorghiade M, Marti CN, Sabbah HN, Roessig L, Greene SJ, B\u00f6hm M, et al. Soluble guanylate cyclase: a potential therapeutic target for heart failure. Heart Failure Reviews. 2013; 18: 123\u2013134.","DOI":"10.1007\/s10741-012-9323-1"},{"key":"ref24","doi-asserted-by":"publisher","unstructured":"Shaikh TG, Jawed S, Rahmat ZS, Ahmed SH, Waseem S, Ullah I, et al. Efficacy and Safety of Vericiguat for Treatment of Heart Failure: A Systematic Review. Current Problems in Cardiology. 2023; 48: 101586.","DOI":"10.1016\/j.cpcardiol.2023.101586"},{"key":"ref25","doi-asserted-by":"publisher","unstructured":"Barouch LA, Harrison RW, Skaf MW, Rosas GO, Cappola TP, Kobeissi ZA, et al. Nitric oxide regulates the heart by spatial confinement of nitric oxide synthase isoforms. Nature. 2002; 416: 337\u2013339.","DOI":"10.1038\/416337a"},{"key":"ref26","doi-asserted-by":"publisher","unstructured":"Hare JM. Nitric oxide and excitation-contraction coupling. Journal of Molecular and Cellular Cardiology. 2003; 35: 719\u2013729.","DOI":"10.1016\/s0022-2828(03)00143-3"},{"key":"ref27","doi-asserted-by":"publisher","unstructured":"Kong Q, Blanton RM. Protein kinase GI and heart failure: shifting focus from vascular unloading to direct myocardial antiremodeling effects. Circulation: Heart Failure. 2013; 6: 1268\u20131283.","DOI":"10.1161\/CIRCHEARTFAILURE.113.000575"},{"key":"ref28","doi-asserted-by":"publisher","unstructured":"Triposkiadis F, Xanthopoulos A, Skoularigis J, Starling RC. Therapeutic augmentation of NO-sGC-cGMP signalling: lessons learned from pulmonary arterial hypertension and heart failure. Heart Failure Reviews. 2022; 27: 1991\u20132003.","DOI":"10.1007\/s10741-022-10239-5"},{"key":"ref29","doi-asserted-by":"publisher","unstructured":"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. Journal of Medicinal Chemistry. 2017; 60: 5146\u20135161.","DOI":"10.1021\/acs.jmedchem.7b00449"},{"key":"ref30","doi-asserted-by":"publisher","unstructured":"Murphy SP, Kakkar R, McCarthy CP, Januzzi JL, Jr. Inflammation in Heart Failure: JACC State-of-the-Art Review. Journal of the American College of Cardiology. 2020; 75: 1324\u20131340.","DOI":"10.1016\/j.jacc.2020.01.014"},{"key":"ref31","doi-asserted-by":"publisher","unstructured":"Marti CN, Gheorghiade M, Kalogeropoulos AP, Georgiopoulou VV, Quyyumi AA, Butler J. Endothelial dysfunction, arterial stiffness, and heart failure. Journal of the American College of Cardiology. 2012; 60: 1455\u20131469.","DOI":"10.1016\/j.jacc.2011.11.082"},{"key":"ref32","doi-asserted-by":"publisher","unstructured":"Stasch JP, Pacher P, Evgenov OV. Soluble guanylate cyclase as an emerging therapeutic target in cardiopulmonary disease. Circulation. 2011; 123: 2263\u20132273.","DOI":"10.1161\/CIRCULATIONAHA.110.981738"},{"key":"ref33","doi-asserted-by":"publisher","unstructured":"Harada T, Kondo H, Nakamura K, He Y, Goto S, Takahashi M, et al. Soluble Guanylate Cyclase Stimulator Vericiguat Attenuates Angiotensin II-Induced Oxidative Stress and Cardiac Remodeling. Circulation Journal: Official Journal of the Japanese Circulation Society. 2025; 89: 982\u2013991.","DOI":"10.1253\/circj.CJ-24-0659"},{"key":"ref34","doi-asserted-by":"publisher","unstructured":"Fiedler B, Lohmann SM, Smolenski A, Linnemuller S, Pieske B, Schroder F, et al. Inhibition of calcineurin-NFAT hypertrophy signaling by cGMP-dependent protein kinase type I in cardiac myocytes. Proceedings of the National Academy of Sciences of the United States of America. 2002; 99: 11363\u201311368.","DOI":"10.1073\/pnas.162100799"},{"key":"ref35","doi-asserted-by":"publisher","unstructured":"Spiecker M, Peng HB, Liao JK. Inhibition of endothelial vascular cell adhesion molecule-1 expression by nitric oxide involves the induction and nuclear translocation of IkappaBalpha. The Journal of Biological Chemistry. 1997; 272: 30969\u201330974.","DOI":"10.1074\/jbc.272.49.30969"},{"key":"ref36","doi-asserted-by":"publisher","unstructured":"Garatti L, Frea S, Bocchino PP, Angelini F, Cingolani M, Sacco A, et al. Sodium nitroprusside in acute heart failure: A multicenter historic cohort study. International Journal of Cardiology. 2022; 369: 37\u201344.","DOI":"10.1016\/j.ijcard.2022.08.009"},{"key":"ref37","doi-asserted-by":"publisher","unstructured":"Bocchino PP, Angelini F, Gallone G, Frea S, De Ferrari GM. The cardiovascular safety of sodium nitroprusside in acute heart failure. Expert Opinion on Drug Safety. 2024; 23: 663\u2013666.","DOI":"10.1080\/14740338.2024.2348570"},{"key":"ref38","doi-asserted-by":"publisher","unstructured":"Gheorghiade M, Greene SJ, Butler J, Filippatos G, Lam CSP, Maggioni AP, et al. 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\u20132262.","DOI":"10.1001\/jama.2015.15734"},{"key":"ref39","doi-asserted-by":"publisher","unstructured":"Boettcher M, Thomas D, Mueck W, Loewen S, Arens E, Yoshikawa K, et al. Safety, pharmacodynamic, and pharmacokinetic characterization of vericiguat: results from six phase I studies in healthy subjects. European Journal of Clinical Pharmacology. 2021; 77: 527\u2013537.","DOI":"10.1007\/s00228-020-03023-7"},{"key":"ref40","doi-asserted-by":"publisher","unstructured":"Pieske B, Maggioni AP, Lam CSP, Pieske-Kraigher E, Filippatos G, Butler J, et al. Vericiguat in patients with worsening chronic heart failure and preserved ejection fraction: results of the SOluble guanylate Cyclase stimulatoR in heArT failurE patientS with PRESERVED EF (SOCRATES-PRESERVED) study. European Heart Journal. 2017; 38: 1119\u20131127.","DOI":"10.1093\/eurheartj\/ehw593"},{"key":"ref41","doi-asserted-by":"publisher","unstructured":"Armstrong PW, Lam CSP, Anstrom KJ, Ezekowitz J, Hernandez AF, O\u2019Connor CM, et al. Effect of Vericiguat vs Placebo on Quality of Life in Patients With Heart Failure and Preserved Ejection Fraction: The VITALITY-HFpEF Randomized Clinical Trial. JAMA. 2020; 324: 1512\u20131521.","DOI":"10.1001\/jama.2020.15922"},{"key":"ref42","doi-asserted-by":"publisher","unstructured":"Armstrong PW, Pieske B, Anstrom KJ, Ezekowitz J, Hernandez AF, Butler J, et al. Vericiguat in Patients with Heart Failure and Reduced Ejection Fraction. The New England Journal of Medicine. 2020; 382: 1883\u20131893.","DOI":"10.1056\/NEJMoa1915928"},{"key":"ref43","doi-asserted-by":"publisher","unstructured":"Packer M, Anker SD, Butler J, Filippatos G, Ferreira JP, Pocock SJ, et al. Effect of Empagliflozin on the Clinical Stability of Patients With Heart Failure and a Reduced Ejection Fraction: The EMPEROR-Reduced Trial. Circulation. 2021; 143: 326\u2013336.","DOI":"10.1161\/CIRCULATIONAHA.120.051783"},{"key":"ref44","doi-asserted-by":"publisher","unstructured":"Butler J, McMullan CJ, Anstrom KJ, Barash I, Bonaca MP, Borentain M, et al. Vericiguat in patients with chronic heart failure and reduced ejection fraction (VICTOR): a double-blind, placebo-controlled, randomised, phase 3 trial. Lancet (London, England). 2025; 406: 1341\u20131350.","DOI":"10.1016\/S0140-6736(25)01665-4"},{"key":"ref45","doi-asserted-by":"publisher","unstructured":"Zannad F, O\u2019Connor CM, Butler J, McMullan CJ, Anstrom KJ, Barash I, et al. Vericiguat for patients with heart failure and reduced ejection fraction across the risk spectrum: an individual participant data analysis of the VICTORIA and VICTOR trials. Lancet (London, England). 2025; 406: 1351\u20131362.","DOI":"10.1016\/S0140-6736(25)01682-4"},{"key":"ref46","doi-asserted-by":"publisher","unstructured":"Greene SJ, Corda S, McMullan CJ, Palombo G, Schooss C, Vlajnic V, et al. Safety and tolerability of a 5 mg starting dose of vericiguat among patients with heart failure: The VELOCITY study. European Journal of Heart Failure. 2025.  (online ahead of print)","DOI":"10.1002\/ejhf.3699"},{"key":"ref47","doi-asserted-by":"publisher","unstructured":"Lam CSP, Giczewska A, Sliwa K, Edelmann F, Refsgaard J, Bocchi E, et al. Clinical Outcomes and Response to Vericiguat According to Index Heart Failure Event: Insights From the VICTORIA Trial. JAMA Cardiology. 2021; 6: 706\u2013712.","DOI":"10.1001\/jamacardio.2020.6455"},{"key":"ref48","doi-asserted-by":"publisher","unstructured":"Reddy YNV, Butler J, Anstrom KJ, Blaustein RO, Bonaca MP, Corda S, et al. Vericiguat Global Study in Participants with Chronic Heart Failure: Design of the VICTOR trial. European Journal of Heart Failure. 2025; 27: 209\u2013218.","DOI":"10.1002\/ejhf.3501"},{"key":"ref49","doi-asserted-by":"publisher","unstructured":"Tromp J, Ouwerkerk W, van Veldhuisen DJ, Hillege HL, Richards AM, van der Meer P, et al. A Systematic Review and Network Meta-Analysis of Pharmacological Treatment of Heart Failure With Reduced Ejection Fraction. JACC. Heart Failure. 2022; 10: 73\u201384.","DOI":"10.1016\/j.jchf.2021.09.004"},{"key":"ref50","doi-asserted-by":"publisher","unstructured":"Shoji S, Mentz RJ. Beyond quadruple therapy: the potential roles for ivabradine, vericiguat, and omecamtiv mecarbil in the therapeutic armamentarium. Heart Failure Reviews. 2024; 29: 949\u2013955.","DOI":"10.1007\/s10741-024-10412-y"},{"key":"ref51","doi-asserted-by":"publisher","unstructured":"Heidenreich PA, Bozkurt B, Aguilar D, Allen LA, Byun JJ, Colvin MM, et al. 2022 AHA\/ACC\/HFSA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology\/American Heart Association Joint Committee on Clinical Practice Guidelines. Journal of the American College of Cardiology. 2022; 79: e263\u2013e421.","DOI":"10.1016\/j.jacc.2021.12.012"},{"key":"ref52","unstructured":"Verquvo \u2014 European Medicines Agency (EMA). 2021. Available at: https:\/\/www.ema.europa.eu\/en\/medicines\/human\/EPAR\/verquvo (Accessed: 10 October 2025)."},{"key":"ref53","doi-asserted-by":"publisher","unstructured":"Butler J, Djatche LM, Lautsch D, Yang L, Patel MJ, Mentz RJ. Representativeness of the VICTORIA Trial Population in Clinical Practice: Analysis of the PINNACLE Registry. Journal of Cardiac Failure. 2021; 27: 1374\u20131381.","DOI":"10.1016\/j.cardfail.2021.06.019"},{"key":"ref54","doi-asserted-by":"publisher","unstructured":"Oh J, Lee CJ, Park JJ, Lee SE, Kim MS, Cho HJ, et al. Real-world eligibility for vericiguat in decompensated heart failure with reduced ejection fraction. ESC Heart Failure. 2022; 9: 1492\u20131495.","DOI":"10.1002\/ehf2.13837"},{"key":"ref55","doi-asserted-by":"publisher","unstructured":"Nguyen NV, Lindberg F, Benson L, Ferrannini G, Imbalzano E, Mol PGM, et al. Eligibility for vericiguat in a real-world heart failure population according to trial, guideline and label criteria: Data from the Swedish Heart Failure Registry. European Journal of Heart Failure. 2023; 25: 1418\u20131428.","DOI":"10.1002\/ejhf.2939"},{"key":"ref56","doi-asserted-by":"publisher","unstructured":"Galv\u00e1n Ruiz M, Fern\u00e1ndez de Sanmamed Gir\u00f3n M, Del Val Groba Marco M, Rojo Jorge L, Pe\u00f1a Saavedra C, Mart\u00edn Bou E, et al. Clinical profile, associated events and safety of vericiguat in a real-world cohort: The VERITA study. ESC Heart Failure. 2024; 11: 4222\u20134230.","DOI":"10.1002\/ehf2.15032"},{"key":"ref57","doi-asserted-by":"publisher","unstructured":"Sepehrvand N, Islam S, Dover DC, Kaul P, McAlister FA, Armstrong PW, et al. Epidemiology of Worsening Heart Failure in a Population-based Cohort from Alberta, Canada: Evaluating Eligibility for Treatment With Vericiguat. Journal of Cardiac Failure. 2022; 28: 1298\u20131308.","DOI":"10.1016\/j.cardfail.2022.04.015"},{"key":"ref58","doi-asserted-by":"publisher","unstructured":"Esteban-Fern\u00e1ndez A, Recio-Mayoral A, L\u00f3pez-Vilella R, de Lara G, Barrantes-Castillo M, G\u00f3mez-Otero I, et al. Clinical profile of an unselected population with heart failure treated with vericiguat in real life: differences with the VICTORIA trial. Frontiers in Cardiovascular Medicine. 2025; 11: 1504427.","DOI":"10.3389\/fcvm.2024.1504427"},{"key":"ref59","doi-asserted-by":"publisher","unstructured":"Okami S, Ohlmeier C, Takeichi M, Aguila M, Holl K, Michel A, et al. Vericiguat Use in Patients with Heart Failure in Real-World Settings during the First Year after the Drug Authorization in Japan. Journal of Clinical Medicine. 2024; 13: 3222.","DOI":"10.3390\/jcm13113222"},{"key":"ref60","doi-asserted-by":"publisher","unstructured":"Hida Y, Imamura T, Kinugawa K. Optimal Timing of Vericiguat Therapy in Patients with Heart Failure with Reduced\/Mildly Reduced Ejection Fraction for Improving Mortality and Heart Failure Re-Hospitalization Rate. Journal of Clinical Medicine. 2025; 14: 5856.","DOI":"10.3390\/jcm14165856"},{"key":"ref61","doi-asserted-by":"publisher","unstructured":"Ezekowitz JA, O\u2019Connor CM, Troughton RW, Alemayehu WG, Westerhout CM, Voors AA, et al. N-Terminal Pro-B-Type Natriuretic Peptide and Clinical Outcomes: Vericiguat Heart Failure With Reduced Ejection Fraction Study. JACC. Heart Failure. 2020; 8: 931\u2013939.","DOI":"10.1016\/j.jchf.2020.08.008"},{"key":"ref62","doi-asserted-by":"publisher","unstructured":"Kerwagen F, Ohlmeier C, Evers T, Herrmann S, Bayh I, Michel A, et al. Real-world characteristics and use patterns of patients treated with vericiguat: A nationwide longitudinal cohort study in Germany. European Journal of Clinical Pharmacology. 2024; 80: 931\u2013940.","DOI":"10.1007\/s00228-024-03654-0"},{"key":"ref63","doi-asserted-by":"publisher","unstructured":"Sandner P, Zimmer DP, Milne GT, Follmann M, Hobbs A, Stasch JP. Soluble Guanylate Cyclase Stimulators and Activators. Handbook of Experimental Pharmacology. 2021; 264: 355\u2013394.","DOI":"10.1007\/164_2018_197"},{"key":"ref64","doi-asserted-by":"publisher","unstructured":"Widmer RJ, Flammer AJ, Lerman LO, Lerman A. The Mediterranean diet, its components, and cardiovascular disease. The American Journal of Medicine. 2015; 128: 229\u2013238.","DOI":"10.1016\/j.amjmed.2014.10.014"},{"key":"ref65","doi-asserted-by":"publisher","unstructured":"Hambrecht R, Fiehn E, Weigl C, Gielen S, Hamann C, Kaiser R, et al. Regular physical exercise corrects endothelial dysfunction and improves exercise capacity in patients with chronic heart failure. Circulation. 1998; 98: 2709\u20132715.","DOI":"10.1161\/01.cir.98.24.2709"},{"key":"ref66","doi-asserted-by":"publisher","unstructured":"Frea S, Gravinese C, Boretto P, De Lio G, Bocchino PP, Angelini F, et al. Comprehensive non-invasive haemodynamic assessment in acute decompensated heart failure-related cardiogenic shock: a step towards echodynamics. European Heart Journal. Acute Cardiovascular Care. 2024; 13: 646\u2013655.","DOI":"10.1093\/ehjacc\/zuae087"},{"key":"ref67","doi-asserted-by":"publisher","unstructured":"Martino TA, Young ME. Influence of the cardiomyocyte circadian clock on cardiac physiology and pathophysiology. Journal of Biological Rhythms. 2015; 30: 183\u2013205.","DOI":"10.1177\/0748730415575246"}],"container-title":["Reviews in Cardiovascular Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.imrpress.com\/journal\/RCM\/27\/4\/10.31083\/RCM48373","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T10:32:37Z","timestamp":1777458757000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.imrpress.com\/journal\/RCM\/27\/4\/10.31083\/RCM48373"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,20]]},"references-count":67,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026]]}},"alternative-id":["S1530-6550(26)02652-0"],"URL":"https:\/\/doi.org\/10.31083\/rcm48373","relation":{},"ISSN":["1530-6550","2153-8174"],"issn-type":[{"value":"1530-6550","type":"print"},{"value":"2153-8174","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,20]]},"article-number":"48373"}}