Riociguat and the right ventricle in pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension

Benza, Raymond L.; Langleben, David; Hemnes, Anna R.; Vonk‐Noordegraaf, Anton; Rosenkranz, Stephan; Thenappan, Thenappan; Hassoun, Paul M.; Preston, Ioana R.; Ghio, Stefano; Badagliacca, Roberto; Vizza, Carmine Dario; Lang, Irene; Meier, Christian; Grünig, Ekkehard

doi:10.1183/16000617.0061-2022

Cited by 7 publications

(5 citation statements)

References 83 publications

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“…These observations suggest improvement of RV contractile function by riociguat regardless of RV loading [ 52 ]. The effects of riociguat on RV structure and function have recently been reviewed [ 53 ].…”

Section: Clinical Data For Sgc Stimulators In Phmentioning

confidence: 99%

The nitric oxide–soluble guanylate cyclase–cGMP pathway in pulmonary hypertension: from PDE5 to soluble guanylate cyclase

Benza,

Grünig,

Sandner

et al. 2024

Eur Respir Rev

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The nitric oxide (NO)–soluble guanylate cyclase (sGC)–cyclic guanosine monophosphate (cGMP) pathway plays a key role in the pathogenesis of pulmonary hypertension (PH). Targeted treatments include phosphodiesterase type 5 inhibitors (PDE5i) and sGC stimulators. The sGC stimulator riociguat is approved for the treatment of pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH). sGC stimulators have a dual mechanism of action, enhancing the sGC response to endogenous NO and directly stimulating sGC, independent of NO. This increase in cGMP productionviaa dual mechanism differs from PDE5i, which protects cGMP from degradation by PDE5, rather than increasing its production. sGC stimulators may therefore have the potential to increase cGMP levels under conditions of NO depletion that could limit the effectiveness of PDE5i. Such differences in mode of action between sGC stimulators and PDE5i could lead to differences in treatment efficacy between the classes. In addition to vascular effects, sGC stimulators have the potential to reduce inflammation, angiogenesis, fibrosis and right ventricular hypertrophy and remodelling. In this review we describe the evolution of treatments targeting the NO–sGC–cGMP pathway, with a focus on PH.

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Section: Clinical Data For Sgc Stimulators In Phmentioning

confidence: 99%

The nitric oxide–soluble guanylate cyclase–cGMP pathway in pulmonary hypertension: from PDE5 to soluble guanylate cyclase

Benza,

Grünig,

Sandner

et al. 2024

Eur Respir Rev

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“…It enhances cGMP levels via two separate mechanisms: first, it stabilizes NO binding to sGC, and second, it directly stimulates sGC independently of NO levels ( Figure 4 ). In the pulmonary circulation, this leads to vascular smooth muscle cell relaxation [ 51 ]. That is the reason why, in the past few years, there has been an increasing interest in riociguat, which has been tested in PAH patients.…”

Section: Modulation Of Pulmonary Vascular No In Pahmentioning

confidence: 99%

Modulating NO–GC Pathway in Pulmonary Arterial Hypertension

D’Agostino,

Lanzafame,

Buono

et al. 2023

IJMS

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The pathogenesis of complex diseases such as pulmonary arterial hypertension (PAH) is entirely rooted in changes in the expression of some vasoactive factors. These play a significant role in the onset and progression of the disease. Indeed, PAH has been associated with pathophysiologic alterations in vascular function. These are often dictated by increased oxidative stress and impaired modulation of the nitric oxide (NO) pathway. NO reduces the uncontrolled proliferation of vascular smooth muscle cells that leads to occlusion of vessels and an increase in pulmonary vascular resistances, which is the mainstay of PAH development. To date, two classes of NO-pathway modulating drugs are approved for the treatment of PAH: the phosphodiesterase-5 inhibitors (PD5i), sildenafil and tadalafil, and the soluble guanylate cyclase activator (sGC), riociguat. Both drugs provide considerable improvement in exercise capacity and pulmonary hemodynamics. PD5i are the recommended drugs for first-line PAH treatment, whereas sGCs are also the only drug approved for the treatment of resistant or inoperable chronic thromboembolic pulmonary hypertension. In this review, we will focus on the current information regarding the nitric oxide pathway and its modulation in PAH.

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“…The positive effects of riociguat have been observed in terms of improved pulmonary artery remodeling, pulmonary hemodynamics, improved RV-PA coupling, improved RV function, reduced RA and RV dimensions, RV hypertrophy and fibrosis, reduced tricuspid regurgitation both in preclinical models and prospective randomized controlled phase III trials such as PATENT-1 and CHEST-1 [ 20 ].…”

Section: Current Perspectives For Treatment Of Pulmonary Arterial Hyp...mentioning

confidence: 99%

Medical Management of Right Ventricular Dysfunction in Pulmonary Arterial Hypertension

Caputo

Papa

Manzi

et al. 2023

Curr Heart Fail Rep

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Purpose of Review The purpose of this review is to overview the most relevant and recent knowledge regarding medical management in pulmonary arterial hypertension (PAH). Recent Findings Evidence has shown that PAH patients’ quality of life and prognosis depend on the capability of the RV to adapt to increased afterload and to fully recover in response to substantially reduced pulmonary vascular resistance obtained with medical therapy. Data from recent clinical studies show that more aggressive treatment strategies, especially in higher risk categories, determine larger afterload reductions, consequentially increasing the probability of achieving right heart reverse remodeling, therefore improving the patients’ survival and quality of life. Remarkable progress has been observed over the past decades in the medical treatment of PAH, related to the development of drugs that target multiple biological pathways, strategies for earlier and more aggressive treatment interventions. Summary New hopes for treatment of patients who are unable to achieve low-risk status have been derived from the phase 2 trial PULSAR and the phase 3 trial STELLAR, which show improvement in the hemodynamic status of patients treated with sotatercept on top of background therapy. Promising results are expected from several ongoing clinical trials targeting new pathways involved in the pathophysiology of PAH.

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Riociguat and the right ventricle in pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension

Cited by 7 publications

References 83 publications

The nitric oxide–soluble guanylate cyclase–cGMP pathway in pulmonary hypertension: from PDE5 to soluble guanylate cyclase

The nitric oxide–soluble guanylate cyclase–cGMP pathway in pulmonary hypertension: from PDE5 to soluble guanylate cyclase

Modulating NO–GC Pathway in Pulmonary Arterial Hypertension

Medical Management of Right Ventricular Dysfunction in Pulmonary Arterial Hypertension

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