Sildenafil for idiopathic pulmonary fibrosis: A systematic review and meta-analysis

Pitre, Tyler; Khalid, Faran; Cui, Sonya; Zhang, Melanie C.; Husnudinov, Renata; Mah, Jasmine; Helmczi, Wryan; Su, Johnny; Guy, Brent; Scallan, Ciaran; Jones, Aaron; Zeraatkar, Dena

doi:10.1016/j.pupt.2022.102128

Cited by 6 publications

(4 citation statements)

References 19 publications

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“…A double-blind randomized clinical trial showed that the combination of Sildenafil and Nintedanib significantly reduced BNP (B-type natriuretic peptide, an indicator of heart failure) in IPF patients with right ventricular dysfunction compared with Nintedanib alone, but did not improve HRQL (Behr et al, 2019;Suarez-Cuartin and Molina-Molina, 2019). More recently, a systematic review and meta-analysis of RCTs reported that Sildenafil probably reduced all-cause mortality in IPF patients (Pitre et al, 2022), although more studies are needed to confirm this. The 2015 ATS/ERS/JRS/ ALAT clinical practice guideline conditionally recommends against the use of Bosentan and Sildenafil, while the 2011 version strongly recommends against the use of them.…”

Section: Information About Clinical Trials That Target Complications ...mentioning

confidence: 99%

Targeting Growth Factor and Cytokine Pathways to Treat Idiopathic Pulmonary Fibrosis

Liu

et al. 2022

Front. Pharmacol.

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Idiopathic pulmonary fibrosis (IPF) is a chronic interstitial lung disease of unknown origin that usually results in death from secondary respiratory failure within 2–5 years of diagnosis. Recent studies have identified key roles of cytokine and growth factor pathways in the pathogenesis of IPF. Although there have been numerous clinical trials of drugs investigating their efficacy in the treatment of IPF, only Pirfenidone and Nintedanib have been approved by the FDA. However, they have some major limitations, such as insufficient efficacy, undesired side effects and poor pharmacokinetic properties. To give more insights into the discovery of potential targets for the treatment of IPF, this review provides an overview of cytokines, growth factors and their signaling pathways in IPF, which have important implications for fully exploiting the therapeutic potential of targeting cytokine and growth factor pathways. Advances in the field of cytokine and growth factor pathways will help slow disease progression, prolong life, and improve the quality of life for IPF patients in the future.

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Section: Information About Clinical Trials That Target Complications ...mentioning

confidence: 99%

Targeting Growth Factor and Cytokine Pathways to Treat Idiopathic Pulmonary Fibrosis

Liu

et al. 2022

Front. Pharmacol.

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“…The drug dilates pulmonary arteries, relaxes pulmonary artery smooth muscle, reduces the proliferation of pulmonary vascular smooth muscle cells and pulmonary vascular remodeling while enhancing right ventricular contraction, and ultimately improves pulmonary circulation. [23][24][25] Current functional studies of sildenafil have focused on the relief of disease, hemodynamics, and exercise tolerance in patients with PH. Previous experiments illustrated that pretreatment with sildenafil effectively prevented PAH induced by APE, whereas acetylcysteine infusion enhanced this beneficial effect by inhibiting oxidative stress and lipid peroxidation.…”

Section: Discussionmentioning

confidence: 99%

Sildenafil improves hemodynamic changes caused by acute pulmonary embolism by inhibiting Rho kinase activity

Wang,

Li,

Yan

et al. 2024

J Int Med Res

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Objective This study examined the effects of sildenafil on acute pulmonary embolism (APE) using a rat model. Methods Sprague–Dawley rats were randomly divided into the sham, pulmonary thromboembolism (PTE), and sildenafil groups. The sham and PTE groups received normal saline once daily via gavage for 14 consecutive days, whereas the sildenafil group received sildenafil (0.5 mg/kg/day) once daily via gavage for 14 consecutive days. Autologous emboli were prepared from blood samples collected from the left femoral artery of rats in each group on day 13, and autologous emboli were injected into the jugular vein cannula of rats in the PTE and sildenafil groups on day 14. Sham-treated rats received the same volume of saline. Right systolic ventricular pressure (RVSP) and mean pulmonary arterial pressure (MPAP) were used to assess pulmonary embolism, and western blotting and enzyme-linked immunosorbent assay were used to detect relevant markers. Results The Rho kinase signaling pathway was significantly activated in rats with APE, and sildenafil significantly inhibited this activation. Conclusions Sildenafil protected against APE through inhibiting Rho kinase activity, thereby reducing pulmonary vasoconstriction and decreasing elevated pulmonary arterial pressure. These findings might provide new ideas for the clinical treatment of acute pulmonary thromboembolism.

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“…The main pathological manifestations of pulmonary hypertension include decreased production of nitric oxide in endothelium, signi cantly increased activity and expression of PDE5 in right ventricular myocardium and pulmonary artery smooth muscle cells. Sildena l selectively inhibits type 5 phosphodiesterase and enhances the nitric oxide/cyclic guanosine monophosphate signaling pathway; it dilates pulmonary arteries, relaxes pulmonary artery smooth muscle, reduces the proliferation of pulmonary vascular smooth muscle cells and pulmonary vascular remodeling while enhancing right ventricular contraction, and ultimately improves pulmonary circulation [19][20][21] . Current functional studies of sildena l have focused on the relief of disease, hemodynamics, and exercise tolerance in PH patients.…”

Section: Discussionmentioning

confidence: 99%

Sildenafil Improves Hemodynamic Changes Caused by Acute Pulmonary Embolism by Inhibiting Rho-kinase Activity

Wang¹,

Li²,

Yan³

et al. 2023

Preprint

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Acute right heart failure and/or circulatory shock caused by a dramatic increase in pulmonary vascular resistance are the main causes of death from acute pulmonary embolism (APE), and drug intervention of neurohumoral factor-mediated pulmonary vasoconstriction may reduce APE-induced hemodynamic disturbances and improve prognosis. Sildenafil is a cGMP specific highly selective inhibitor of phosphodiesterase type 5 (PDE5) and its main mechanism of action is vasodilator effect via cGMP. In our study, the results showed that Rho kinase signaling pathway was activated during APE in rats, and sildenafil intervention inhibited the activation of Rho kinase signaling pathway in APE rats, elucidating the mechanism of sildenafil protection against APE and providing new ideas for the clinical treatment of acute pulmonary thromboembolism.

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Sildenafil for idiopathic pulmonary fibrosis: A systematic review and meta-analysis

Cited by 6 publications

References 19 publications

Targeting Growth Factor and Cytokine Pathways to Treat Idiopathic Pulmonary Fibrosis

Targeting Growth Factor and Cytokine Pathways to Treat Idiopathic Pulmonary Fibrosis

Sildenafil improves hemodynamic changes caused by acute pulmonary embolism by inhibiting Rho kinase activity

Sildenafil Improves Hemodynamic Changes Caused by Acute Pulmonary Embolism by Inhibiting Rho-kinase Activity

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