Medications for the treatment of pulmonary arterial hypertension: a systematic review and network meta-analysis

Pitre, Tyler; Su, Johnny; Cui, Sonya; Scanlan, Ryan; Chiang, Christopher; Husnudinov, Renata; Khalid, Faran; Khan, Nadia; Leung, Gareth; Mikhail, David; Saadat, Pakeezah; Shahid, Shaneela; Mah, Jasmine; Mielniczuk, Lisa; Zeraatkar, Dena; Mehta, Sanjay

doi:10.1183/16000617.0036-2022

Cited by 16 publications

(4 citation statements)

References 79 publications

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“…Among the 120 that mentioned intransitivity, 28.3% (34/120)11–43 noted that they considered effect modification as the relevant issue when addressing intransitivity. Of these 34, 67.6% (23/34)11–13 15 17 19–21 23–29 32 34–37 39 40 44 further specified which factors they considered as effect modifiers, none of which specified how they identified effect modifiers. The number of effect modifiers listed ranged from 1 to 9 (median 3).…”

Section: Resultsmentioning

confidence: 99%

“…Two SRs13 19 included tables that presented mean, median or mode of effect modifiers for each head-to-head comparison; however, it is unclear how these were calculated and how authors used them to inform rating down for intransitivity. Five SRs,15 26 34 40 44 to inform whether to rate down for intransitivity, explored the impact of effect modifiers on effect estimates by conducting network meta-regression analyses. Two SRs explored the impact of effect modifiers by conducting sensitivity analysis 52 53.…”

Section: Resultsmentioning

confidence: 99%

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How do network meta-analyses address intransitivity when assessing certainty of evidence: a systematic survey

Wang,

Xia,

Pericic

et al. 2023

BMJ Open

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ObjectivesTo describe how systematic reviews with network meta-analyses (NMAs) that used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) NMA approach addressed intransitivity when assessing certainty of evidence.DesignSystematic survey.Data sourcesMedline, Embase and Cochrane Database of Systematic Reviews from September 2014 to October 2022.Eligibility criteriaSystematic reviews of randomised controlled trials with aggregate data NMAs that used the GRADE NMA approach for assessing certainty of evidence.Data extraction and synthesisWe documented how reviewers described methods for addressing intransitivity when assessing certainty of evidence, how often they rated down for intransitivity and their explanations for rating down.ResultsOf the 268 eligible systematic reviews, 44.8% (120/268) mentioned intransitivity when describing methods for assessing the certainty of evidence. Of these, 28.3% (34/120) considered effect modifiers and from this subset, 67.6% (23/34) specified the effect modifiers; however, no systematic review noted how they chose the effect modifiers. 15.0% (18/120) mentioned looking for differences between the direct comparisons that inform the indirect estimate. No review specified a threshold for difference in effect modifiers between the direct comparisons that would lead to rating down for intransitivity. Reviewers noted rating down indirect evidence for intransitivity in 33.1% of systematic reviews, and noted intransitivity for network estimates in 23.0% of reviews. Authors provided an explanation for rating down for intransitivity in 59.6% (31/52) of the cases in which they rated down. Of the 31 in which they provided an explanation, 74.2% (23/31) noted they detected differences in effect modifiers and 67.7% (21/31) specified in what effect modifiers they detected differences.ConclusionsA third of systematic reviews with NMAs using the GRADE approach rated down for intransitivity. Limitations in reporting of methods to address intransitivity proved considerable. Whether the problem is that reviewers neglected to address rating down for transitivity at all, or whether they did consider but not report, is not clear. At minimum systematic reviews with NMAs need to improve their reporting practices regarding intransitivity; it may well be that they need to improve their practice in transitivity assessment. How to best address intransitivity may remain unclear for many reviewers thus additional GRADE guidance providing practical instructions for addressing intransitivity may be desirable.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

How do network meta-analyses address intransitivity when assessing certainty of evidence: a systematic survey

Wang,

Xia,

Pericic

et al. 2023

BMJ Open

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“…12 However, there is no consensus on which drug is most associated with long-term survival in PAH patients among pulmonary vasodilators targeting the same biological pathway. 13 Although head-to-head trials directly comparing all drugs in the same category are required, it is difficult to comprehensively conduct large-scale clinical trials comparing all PAH-specific vasodilators targeting the same biological pathway due to PAH being a rare disease. 14 Exploratory analysis using RWD is an efficient approach for comparing the effects of PAH-specific vasodilators on long-term survival prior to conducting clinical trials.…”

Section: Introductionmentioning

confidence: 99%

Long-term efficacies of selective vasodilators in pulmonary arterial hypertension: A comprehensive comparison using a spontaneous reporting database

Suzuki

Yagi

Kawakami

2023

Preprint

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Aims: There is no clinical evidence of differences in drugs associated with long-term survival in patients with pulmonary arterial hypertension (PAH) due to a small population and the lack of information on death in the Japanese medical database systems. This study evaluated whether patient data from a spontaneous reporting database could be used for comparing the effects of pulmonary vasodilators on long-term survival in PAH patients. Methods: PAH patient data reported in the Japanese Adverse Drug Event Report (JADER) database from April 2004 to July 2022 were extracted. Kaplan-Meier curves were used to compare survival times. Adjusted hazard ratios (aHRs) for all-cause mortality were determined using Cox proportional hazards models. Results: Of 1969 PAH patients reported in the JADER database, 1208 patients were included in the survival analyses. The patient demographics were similar to those of the PAH population reported in the Japan Pulmonary Hypertension Registry. Among drugs targeting the prostacyclin pathway, epoprostenol was most associated with long-term survival (aHR: 0.38; 95% confidence interval [CI], 0.23–0.64). The PAH patients treated with endothelin receptor antagonists had improved survival, especially in the macitentan users (aHR: 0.30; 95% CI, 0.22–0.42). Sildenafil was associated with a poor prognosis in the PAH patients (aHR: 1.56; 95% CI, 1.19–2.04). Conclusion: Although our results must be interpreted with caution due to several limitations inherent to spontaneous reporting databases, our approach using the JADER database for survival analysis may provide useful information in limited situations such as the treatment of rare diseases including PAH.

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“…10 Its sibling riociguat is used extensively as an independent of NO simulator of soluble guanylate cyclase (sGC). 11 Besides above examples, molecules with the pyrazolo [3,4-b]pyridine core have been used for the treatment of gastrointestinal diseases, 12 Alzheimer disease 13 alcohol withdrawal symptoms 14 and erectile dysfunction. 15 Specifically, molecules built on this scaffold have been reported as selective inhibitors of A1 adenosine Although the pyrazolo [3,4-b]pyridine structure can be assembled by a variety of methods, condensation of N(1) substituted 5-aminopyrazoles with 1,3-bis-electrophilic three-carbon synthons is the popular choice (Equation 1, Scheme 1).…”

Section: Introductionmentioning

confidence: 99%

Design, Synthesis, Molecular Docking and Biological Activity of Pyrazolo[3,4-b]pyridines as Promising Lead Candidates AgainstMycobacterium tuberculosis

Rao,

Gunasundari,

Adigopula

et al. 2023

Preprint

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Pyrazolo[3,4-b]pyridine is a medicinally privileged structure. We have achieved a new and facile synthesis of a combinatorial library of its tetra- and persubstituted derivatives by trifluoracetic acid catalysed condensation of a group of 5-aminopyrazoles and a group of alpha-oxoketene dithioacetals. Furthermore, we demonstrated structural modification of the products via reductive desulfurization, hydrolysis of the ester and Suzuki coupling of the bromo derivative with aryl bornoic acids. Some of the products were subjected to in vitro MABA assay against M. tuberclulosis H37Rv strain and in silico analysis by binding to pantothenate synthetase from M. tuberclulosis (MTBPS). The results indicated that the pyazolo[3,4-b]pyridine with N(1)CH3, C(3)C6H5, C(4) pCH3C6H5, C(5)CO2Et, C(6)SMe substitutions exhibits promising antituberculotic activity.

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Medications for the treatment of pulmonary arterial hypertension: a systematic review and network meta-analysis

Cited by 16 publications

References 79 publications

How do network meta-analyses address intransitivity when assessing certainty of evidence: a systematic survey

How do network meta-analyses address intransitivity when assessing certainty of evidence: a systematic survey

Long-term efficacies of selective vasodilators in pulmonary arterial hypertension: A comprehensive comparison using a spontaneous reporting database

Design, Synthesis, Molecular Docking and Biological Activity of Pyrazolo[3,4-b]pyridines as Promising Lead Candidates AgainstMycobacterium tuberculosis

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