Comprehensive review on novel targets and emerging therapeutic modalities for pulmonary arterial Hypertension

Dhoble, Sagar; Patravale, Vandana; Weaver, Edward; Lamprou, Dimitrios A.; Patravale, Tanmay

doi:10.1016/j.ijpharm.2022.121792

Cited by 21 publications

(16 citation statements)

References 174 publications

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“…Therefore, the three major classical pathway drugs are still mainly used clinically to treat PAH, and these traditional methods still have a high mortality rate, although they alleviate the symptoms to some extent. Nanomedicines and gene therapy are emerging approaches for the treatment of PAH in the future, but a higher level of evidence is needed to reach the goal of individualized treatment ( 49 ). In the meta-regression analysis, there is a correlation between CWEs and the change in 6MWD ( p = 0.032; Figure 3 ), which possibly emphasizes the need to monitor CWEs.…”

Section: Discussionmentioning

confidence: 99%

Effects of oral targeted treatments in pulmonary arterial hypertension: A systematic review and meta-analysis

Zhu

Kuang

et al. 2022

Front. Cardiovasc. Med.

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BackgroundAlthough pulmonary arterial hypertension (PAH) is a fatal disease, specific drugs have been used to treat PAH. These drugs predominantly target these three pathobiological pathways: Endothelin receptor antagonist (ERA), nitric oxide (NO), and prostanoids pathways. In this review, we aimed to analyze the efficacy and safety of oral targeted treatments for PAH.MethodsThe national library of medicine (MEDLINE), excerpta medica database (EMBASE), and Cochrane Central Register of Controlled Trials databases were searched. Randomized controlled trials that compared the oral targeted drugs with placebos were selected. We calculated odds ratios (ORs) with 95% confidence intervals (CIs) for variables with dichotomous outcomes, and standardized mean differences with continuous outcomes variables. Additionally, the mean of the differences for the 6-min walk distance (6MWD) was analyzed.ResultsIn total, 23 studies involving 7,121 patients were included in this study. These studies show that orally PAH-specific drugs could decrease the risk of clinical worsening events, with an OR of 0.55 (p < 0.001). Furthermore, these drugs could improve exercise capacity, showing a 21.74-m increase in 6MWD (95% CI: 17.53–25.95 m) and cause a greater amelioration of functional class (OR = 0.60, 95% CI: 0.47–0.76). Additionally, subgroup analysis indicated that compared with placebo, ERAs, and drugs in the NO pathway were most effective and safe, which are associated with an improvement in exercise capacity, 6MWD, and worsening events-free survival rate.ConclusionNitric oxide exhibited the most prominent clinical effect on exercise tolerance. However, in the subgroup analysis, oral targeted drugs of different pathways show applicability to different populations, which highlights the need for precise treatment in the clinical setting.Systematic Review Registration[https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=297946], identifier [CRD 42022297946].

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Section: Discussionmentioning

confidence: 99%

Effects of oral targeted treatments in pulmonary arterial hypertension: A systematic review and meta-analysis

Zhu

Kuang

et al. 2022

Front. Cardiovasc. Med.

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“…The potency of nilotinib is 20–50 times greater than imatinib, and a phase II study to establish safety with this drug was terminated due to serious adverse events [ 11 , 28 ]. Dasatinib , a PDGF receptor inhibitor, was the only member of the TKI family to have a negative effect on PAH treatment [ 11 , 93 ]. This drug has been reported to induce PAH in multiple cases [ 28 ].…”

Section: Novel Therapiesmentioning

confidence: 99%

New Drugs and Therapies in Pulmonary Arterial Hypertension

Shah

Beckmann

Vorla

2023

IJMS

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Pulmonary arterial hypertension is a chronic, progressive disorder of the pulmonary vasculature with associated pulmonary and cardiac remodeling. PAH was a uniformly fatal disease until the late 1970s, but with the advent of targeted therapies, the life expectancy of patients with PAH has now considerably improved. Despite these advances, PAH inevitably remains a progressive disease with significant morbidity and mortality. Thus, there is still an unmet need for the development of new drugs and other interventional therapies for the treatment of PAH. One shortcoming of currently approved vasodilator therapies is that they do not target or reverse the underlying pathogenesis of the disease process itself. A large body of evidence has evolved in the past two decades clarifying the role of genetics, dysregulation of growth factors, inflammatory pathways, mitochondrial dysfunction, DNA damage, sex hormones, neurohormonal pathways, and iron deficiency in the pathogenesis of PAH. This review focuses on newer targets and drugs that modify these pathways as well as novel interventional therapies in PAH.

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“…Investigating novel molecular targets for the disease is crucial given the various processes underpinning the PAH pathogenesis. More recent molecular pathways may speed up the introduction of newer PAH drugs and eliminate the requirement for the combinational drugs now required to obtain desired treatment effects [31].…”

Section: New Molecular Targets For Pah: a Different Perspectivementioning

confidence: 99%

“…Figure 3 shows the various newer molecular targets for the treatment of PAH. The image is adapted from Dhoble et al [31].…”

Section: New Molecular Targets For Pah: a Different Perspectivementioning

confidence: 99%

Therapeutic Use of an Inhaled Drug Delivery in Pulmonary Hypertension: A Review

Kumbhare¹,

Yelne²,

Tekale³

2022

Cureus

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Pulmonary arterial hypertension (PAH) is a serious condition in which there is increased blood pressure in arteries of the lungs (pulmonary arteries). The therapies or drugs for PAH have expanded with the revelation of three key pathological processes -encompassing prostacyclin, nitric oxide (NO), and endothelin pathways. An outlook for patients suffering from PAH is still mediocre amidst recent advancements. The evolution of pre-clinical and clinical research on PAH has facilitated the identification of several new targeted therapies for the disease. In this article, we examine recent data on new pulmonary hypertension physiological pathways, primarily concentrating on administering drugs through the inhalation route and their effects. Although they have been given clinical use approval, medications based on these routes are presently being studied in clinical or pre-clinical settings. To confirm these innovative medicines' therapeutic efficacy and safety, extensive clinical trials are needed.

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Comprehensive review on novel targets and emerging therapeutic modalities for pulmonary arterial Hypertension

Cited by 21 publications

References 174 publications

Effects of oral targeted treatments in pulmonary arterial hypertension: A systematic review and meta-analysis

Effects of oral targeted treatments in pulmonary arterial hypertension: A systematic review and meta-analysis

New Drugs and Therapies in Pulmonary Arterial Hypertension

Therapeutic Use of an Inhaled Drug Delivery in Pulmonary Hypertension: A Review

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