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 Table of Contents  
Year : 2022  |  Volume : 8  |  Issue : 1  |  Page : 70-71

New year – A newer avenue for heart failure pharmacotherapy

1 Department of Cardiac Anaesthesia, Sri Jayadeva Institute of Cardiovascular Sciences and Research, Bengaluru, Karnataka, India
2 Department of Cardiac Anaesthesia, Atal Bihari Vajpayee Institute of Medical Sciences and Dr. Ram Manohar Lohia Hospital, New Delhi, India
3 Department of Cardiology, L.P.S. Heart Disease Centre, GSVM Medical College, Kanpur, Uttar Pradesh, India

Date of Submission03-Jan-2022
Date of Decision24-Mar-2022
Date of Acceptance25-Mar-2022
Date of Web Publication26-Apr-2022

Correspondence Address:
Sparsh Anil Bhalla
Department of Cardiology, L.P.S. Heart Disease Centre, GSVM Medical College, Kanpur - 208 019, Uttar Pradesh
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jpcs.jpcs_1_22

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How to cite this article:
Jose J, Shri I, Magoon R, Bhalla SA. New year – A newer avenue for heart failure pharmacotherapy. J Pract Cardiovasc Sci 2022;8:70-1

How to cite this URL:
Jose J, Shri I, Magoon R, Bhalla SA. New year – A newer avenue for heart failure pharmacotherapy. J Pract Cardiovasc Sci [serial online] 2022 [cited 2023 Mar 30];8:70-1. Available from: https://www.j-pcs.org/text.asp?2022/8/1/70/344124

Dear Editor,

Heart failure (HF) is a recrudescence with multifactorial etiology which contributes substantially to the overall cardiovascular-related morbidity-mortality burden.[1] Needless to say, the domain of HF pharmacotherapy has considerably evolved through the past few decades, owing to an augmented comprehension of the underlying pathophysiology. Appropriate to the context, the HF pharmacotherapy armamentarium has witnessed another welcome and an equally promising inclusion in the form of vericiguat, that received the Food and Drug Administration (FDA) approval in 2021 for use in adults with symptomatic chronic HF and ejection fraction (EF) <45%.[2]

Delving into the HF pathophysiology, one discovers that soluble guanylate cyclase (sGC) tends to be inactivated by the reactive oxygen species, at a rather enhanced pace in patients with cardiovascular risk factors. The aforementioned leads to impaired muscle relaxation resulting in decreased cardiac compliance. It is noteworthy that vericiguat not only sensitizes sGC to nitric oxide (NO) but also stimulates sGC independent of the NO pathway, i.e., in the face of low NO levels and oxidative stress.[3]

Due to this unique direct acting mechanism on sGC, the newer drug likely emerges as a more selective agent than the conventionally used agents such as nitrates and phosphodiesterase type-5 inhibitors.[4] It additionally possesses a lower pharmacokinetic variability (elimination half-life of 30 h) thereby permitting a once-daily administration in comparison to thrice daily required with its older sibling, riociguat, which can potentially improve the patient compliance (a major practical concern, often overlooked).[4] The VICTORIA trial comparing vericiguat to placebo concluded that the intervention group had a significantly lower incidence of death from cardiovascular causes and hospitalization for HF.[5] Notably, SOCRATES-PRESERVED trial conducted in patients with HF with preserved EF observed that while vericiguat did not alter mortality rate, it significantly improved quality of life and rehospitalization rates.[6] According to the SOCRATES-REDUCED trial, vericiguat was well tolerated at higher doses without significant adverse effects, however, the primary endpoint of reduction in natriuretic endpoint was not achieved or serious adverse effects (SAEs) in patients HF with reduced EF. A meta-analysis by Zheng et al. also concluded that sGC agonists would improve quality of life, are well tolerated, without an excess in drug-related SAEs and have no effect on mortality.[7]

A subgroup analysis of the VICTORIA trial cohort by Lam et al. studying the vericiguat effect on blood pressure and safety profile in vulnerable subgroups concluded a slight decrease in systolic blood pressure occurring at the initiation of therapy although the incidence of symptomatic hypotension and syncope was not significant.[8] A similar subanalysis of the VICTORIA trial noticed statistically significant anemia (<13.0 g/dL in men and <12.0 g/dL in women) at 16 weeks in the vericiguat group compared to placebo.[9] Notably, an FDA boxed warning was added in view of the drug-related embryo-fetal toxicity thereby restricting its use in pregnant women.[2] From a practical standpoint, an additional reduction in blood pressure can transpire in patients concomitantly receiving sildenafil or long-acting nitrates.

Given the rising burden of HF and its pernicious effect on individual patients as well as resource-limited developing economies, it is pertinent to strategize a preventative and an overall cost-effective management strategy. While the development of easy to administer pharmacotherapy is quintessential to successful HF management, inclusion of novel drugs like vericiguat can potentially contribute an enhanced efficacy to the HF-therapeutic strategy by reducing the hospital admissions and improving the quality of life, providing HF patients with a new glimmer of hope.

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Conflicts of interest

There are no conflicts of interest.

  References Top

Ziaeian B, Fonarow GC. Epidemiology and aetiology of heart failure. Nat Rev Cardiol 2016;13:368-78.  Back to cited text no. 1
U.S. Food & Drug Administration. Drug Approvals and Databases: Drug Trials Snapshot: VERQUVO. Available from: https://www.fda.gov/drugs/drug-approvals-and-databases/drug-trials-snapshot- verquvo. [Last updated on 2021 Aug 08; accessed on 2021 Dec 20].  Back to cited text no. 2
Stasch JP, Pacher P, Evgenov OV. Soluble guanylate cyclase as an emerging therapeutic target in cardiopulmonary disease. Circulation 2011;123:2263-73.  Back to cited text no. 3
Armstrong PW, Roessig L, Patel MJ, Anstrom KJ, Butler J, Voors AA, 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.  Back to cited text no. 4
Lam CS, 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 Cardiol 2021;6:706-12.  Back to cited text no. 5
Pieske B, Maggioni AP, Lam CS, 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. Eur Heart J 2017;38:1119-27.  Back to cited text no. 6
Zheng X, Zheng W, Xiong B, Huang J. The efficacy and safety of soluble guanylate cyclase stimulators in patients with heart failure: A systematic review and meta-analysis. Medicine (Baltimore) 2018;97:e12709.  Back to cited text no. 7
Lam CS, Mulder H, Lopatin Y, Vazquez-Tanus JB, Siu D, Ezekowitz J, et al. Blood pressure and safety events with vericiguat in the VICTORIA Trial. J Am Heart Assoc 2021;10:e021094.  Back to cited text no. 8
Ezekowitz JA, Zheng Y, Cohen-Solal A, Melenovský V, Escobedo J, Butler J, et al. Hemoglobin and clinical outcomes in the vericiguat global study in patients with heart failure and reduced ejection fraction (VICTORIA). Circulation 2021;144:1489-99.  Back to cited text no. 9


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