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Frontiers in Cardiovascular Medicine 2022There is little evidence of the effectiveness of switching from the endothelin receptor antagonists (ERAs) bosentan and ambrisentan to a novel ERA, macitentan, in...
BACKGROUND
There is little evidence of the effectiveness of switching from the endothelin receptor antagonists (ERAs) bosentan and ambrisentan to a novel ERA, macitentan, in patients with pulmonary arterial hypertension (PAH). Therefore, a systematic review and meta-analysis was performed to evaluate the efficacy and safety of patients with PAH switching from other ERAs to macitentan.
METHODS
We retrieved the relevant literature published before January 2022 for the meta-analysis from the PubMed, EMBASE, and Cochrane Library databases. Efficacy included changes in the 6-min walk distance (6MWD), World Health Organization functional class (WHO-FC), N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, hemodynamics, echocardiography and survival.
RESULTS
Nine studies, consisting of 408 PAH patients, that met the inclusion criteria were included. The switch from bosentan or ambrisentan to macitentan effectively increased the 6MWD by 20.71 m (95% CI: 10.35-31.07, < 0.00001, = 0%). Six months after conversion, the tricuspid annular plane systolic excursion was found to improve from 19.0 ± 4.0 to 21.0 ± 5.0 mm in adults and from 16.00 ± 5.0 to 18.25 ± 4.8 mm in children. Ordinal logistic regression showed that the WHO-FC significantly improved by 0.412 (95% CI: 0.187-0.908, = 0.028). The switch did not show significant improvement in NT-proBNP levels. In addition, the switch was well tolerated.
CONCLUSION
The switch from bosentan or ambrisentan to macitentan significantly increased the 6MWD in PAH patients, improved the WHO-FC, and exerted safety benefits. The effects of the switch on NT-proBNP levels, hemodynamics, and echocardiography still need to be further confirmed.
SYSTEMATIC REVIEW REGISTRATION
[https://www.crd.york.ac.uk/prospero/], identifier [CRD42021292554].
PubMed: 36568539
DOI: 10.3389/fcvm.2022.977110 -
Journal of Research in Medical Sciences... 2023The aim of the present systematic review and meta-analysis was to evaluate the therapeutic efficacy of bosentan, a dual endothelin receptor antagonist, for systemic... (Review)
Review
BACKGROUND
The aim of the present systematic review and meta-analysis was to evaluate the therapeutic efficacy of bosentan, a dual endothelin receptor antagonist, for systemic sclerosis (SSc) patients with digital ulcers (DUs).
MATERIALS AND METHODS
A systematic search of MEDLINE, Embase, Web of Science, and Scopus was done using appropriate keywords till September 2021. Weighted mean difference (WMD) as the effect of therapeutic efficacy of bosentan on continuous outcomes was an estimate. Furthermore, the pooled prevalence of diffuse SSc and limited SSc was computed. Fixed or random effects models when appropriate were used for data synthesis.
RESULTS
Totally, 469 patients, with a mean age ranging from 48.1 to 63.7 years, from 8 studies were included in the systematic review and meta-analysis. The pooled frequency of diffuse SSc and limited SSc was 56% (95% confidence interval [CI]: 39%, 73%) and 44% (95% CI: 27%, 61%). The pooled prevalence of new DUs following bosentan treatment was 21% (95% CI: 10%, 33%). The results of the meta-analysis showed a pooled mean decrease of WMD: -0.09 (95% CI: -0.020, 0.02, = 0.10), WMD: -2.82 (95% CI: -5.91, 0.27, = 0.07), and WMD: -6.65 (95% CI: -9.49, -3.82, < 0.001) in mean SSc-Health Assessment Questionnaire, pain, and Rodnan score, respectively. Our meta-analysis also indicated a significant pooled decrease in the number of new DUs in SSc patients compared to placebo subjects (WMD: -0.89 [95% CI: -1.40, -0.37; = 0.001]) and baseline values (WMD: -1.34 (95% CI: -1.95, -0.73; < 0.001).
CONCLUSION
Bosentan possibly is an efficacious treatment option for SSc-related DUs. Although further large-scale randomized clinical trials are required to confirm the preliminary finding and underlying mechanisms of action.
PubMed: 36974107
DOI: 10.4103/jrms.jrms_386_22 -
International Heart Journal Jul 2016Pulmonary arterial hypertension (PAH) is a disease that imposes a significant burden on patients. Although multiple treatment options for PAH are available, head-to-head... (Review)
Review
Pulmonary arterial hypertension (PAH) is a disease that imposes a significant burden on patients. Although multiple treatment options for PAH are available, head-to-head comparisons are difficult to conduct. Network meta-analysis (NMA) can be a useful alternative for direct comparison to estimate the relative effectiveness of multiple treatments. The objective of the present study was to conduct a systematic review and NMA to evaluate the relative effectiveness among oral PAH medications.Data collection was performed by searching the Cochrane Central Register of Controlled Trials (CENTRAL) and Ichushi-Web. Randomized controlled trials (RCTs) assessing at least 1 of the following 3 outcome measurements; 6-minute walk distance test (6MWD), WHO functional class (WHOFC), and mean pulmonary artery pressure (mPAP) were included (PROSPERO registration number: CRD42015016557). Outcomes were evaluated by estimating the differences in the mean change from baseline or by estimating the odds ratios. Analyses were performed using WinBUGS 1.4.3.Seven double-blind RCTs were eligible. NMA results showed similar improvements in 6MWD for all medications assessed. Bosentan and sildenafil caused a statistically significant improvement in WHOFC compared to other medications.The relative effectiveness of oral PAH medications could be compared using NMA, which suggested the superiority of bosentan and sildenafil in the improvement of WHOFC.
Topics: Administration, Oral; Antihypertensive Agents; Bosentan; Drug Therapy, Combination; Humans; Hypertension, Pulmonary; Randomized Controlled Trials as Topic; Sildenafil Citrate; Sulfonamides; Treatment Outcome; Vasodilator Agents
PubMed: 27385603
DOI: 10.1536/ihj.15-459 -
European Review For Medical and... 2014In this study, we performed a systematic review and meta-analysis of oral bosentan in adult congenital heart disease associated pulmonary arterial hypertension (CHD-PAH)... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
In this study, we performed a systematic review and meta-analysis of oral bosentan in adult congenital heart disease associated pulmonary arterial hypertension (CHD-PAH) to evaluate its safety and tolerability.
MATERIALS AND METHODS
Online electronic database including PubMed, EMBASE and Springer were searched from October 2006 to October 2013 to collect the clinical studies or cohort trials on CHD-PAH with bosentan treatment. Weight Mean Difference (WMD) and Standard Mean Difference (SMD) were used to evaluate the treatment safety and tolerability. Review Manager (RevMan) version 5.0 was performed for the data analysis.
RESULTS
Totally 8 studies including 215 patients with CHD-PAH were enrolled in this research. With a period of 3-6 months oral bosentan treatment in patients, there were no significant differences in the scores of resting oxygen saturation (Resting SpO2), post-6-MWT SpO2 after 6-minutes' walktest (6-MWT) and Borg dyspnea index score (BDIs) compared with the baseline; the walking distance on 6-MWT increased significantly. With a period of one year or more oral bosentan treatment, the scores of resting SpO2 and post-6-MWT SpO2 increased significantly; there was no significant difference in BDIs and walking distance on 6-MWT.
CONCLUSIONS
The short-term treatment with oral bosentan could increase walking distance on 6-MWT, and long-term treatment could increase the Resting SpO2 in CHD-PAH patients. Oral bosentan in CHD-PAH patients was safe and well tolerated.
Topics: Administration, Oral; Adult; Antihypertensive Agents; Bosentan; Drug Evaluation; Female; Heart Defects, Congenital; Humans; Hypertension, Pulmonary; Male; Sulfonamides
PubMed: 24668703
DOI: No ID Found -
Medicine Mar 2018Oral bosentan has been widely applied in pulmonary arterial hypertension associated with congenital heart disease (PAH-CHD). A systemic review and meta-analysis was... (Meta-Analysis)
Meta-Analysis Review
The efficiency of endothelin receptor antagonist bosentan for pulmonary arterial hypertension associated with congenital heart disease: A systematic review and meta-analysis.
BACKGROUND
Oral bosentan has been widely applied in pulmonary arterial hypertension associated with congenital heart disease (PAH-CHD). A systemic review and meta-analysis was conducted for a therapeutic evaluation of oral bosentan in both adult and pediatric patients with PAH-CHD. The acute responses and a long-term effect were respectively assessed in a comparison with baseline characteristics, and the improvement of exercise tolerance was analyzed.
METHODS
PubMed, Medline, Embase, and Cochrane Central Register of clinical controlled trails or observational studies have been searched for a recording of bosentan effects on the PAH-CHD participants. For mortality and rate of adverse events (AEs), it was described in detail. Randomized-effects model or fixed-effects model was used to calculate different effective values with a sensitivity analysis.
RESULTS
Seventeen studies were pooled in this review, and 3 studies enrolled the pediatric patients. Among all studies, 456 patients were diagnosed with PAH-CHD, and 91.7% were treated with oral bosentan. With a term less than 6 months of bosentan therapy, there existed a significant improvement in 6-minute walk distance (6MWD) and the World Health Organization functional class (WHO-FC), but no such differences in Borg dyspnea index scores (BDIs) and the resting oxygen saturation (SpO2). Although with a prolonged treatment, not only 6MWD and FC, but also the resting SpO2 and heart rate were changed for a better exercise capability. Additionally, compared with the basic cardiopulmonary hemodynamics, it showed a statistically significant difference in mean pulmonary arterial pressure (mPAP) and pulmonary vascular resistance index (PVRi). Although a limitation of pooled studies with comparative outcomes of different terms, outcomes presented a lower WHO-FC which contributes to a success in a prolonged treatment.
CONCLUSIONS
Bosentan in PAH-CHD is well established and still requires clinical trials for an identification of its efficiency on CHD patients for an optimized period lessening a serious complication and the common AEs.
Topics: Adolescent; Adult; Bosentan; Child; Child, Preschool; Endothelin Receptor Antagonists; Familial Primary Pulmonary Hypertension; Heart Defects, Congenital; Humans; Infant; Middle Aged; Sulfonamides; Treatment Outcome; Young Adult
PubMed: 29517668
DOI: 10.1097/MD.0000000000010075 -
Health Technology Assessment... Oct 2009To investigate the clinical and cost-effectiveness of epoprostenol, iloprost, bosentan, sitaxentan and sildenafil for the treatment of adults with pulmonary arterial... (Review)
Review
Clinical and cost-effectiveness of epoprostenol, iloprost, bosentan, sitaxentan and sildenafil for pulmonary arterial hypertension within their licensed indications: a systematic review and economic evaluation.
OBJECTIVE(S)
To investigate the clinical and cost-effectiveness of epoprostenol, iloprost, bosentan, sitaxentan and sildenafil for the treatment of adults with pulmonary arterial hypertension (PAH) within their licensed indications.
DATA SOURCES
Major electronic databases (including the Cochrane Library, MEDLINE and EMBASE) were searched up to February 2007. Further data were obtained from dossiers submitted to NICE by the manufacturers of the technologies.
REVIEW METHODS
The systematic clinical and economic reviews were conducted according to accepted procedures. Model-based economic evaluations of the cost-effectiveness of the technologies from the perspective of the UK NHS and personal social services were carried out.
RESULTS
In total, 20 randomised controlled trials (RCTs) were included in this assessment, mostly of 12-18 weeks duration and comparing one of the technologies added to supportive treatment with supportive treatment alone. Four published economic evaluations were identified. None produced results generalisable to the NHS. There was no consensus in the industry submissions on the most appropriate model structure for the technology assessment. Improvement in 6-minute walk distance (6MWD) was seen with intravenous epoprostenol in primary pulmonary hypertension (PPH) patients with mixed functional class (FC) (mainly III and IV, licensed indication) compared with supportive care (58 metres; 95% CI 6-110). For bosentan compared with supportive care, the pooled result for improvement in 6MWD for FCIII patients with mixed PAH (licensed indication) was 59 metres (95% CI 20-99). For inhaled iloprost, sitaxentan and sildenafil no stratified data for improvement in 6MWD were available. The odds ratio (OR) for FC deterioration at 12 weeks was 0.40 (95% CI 0.13-1.20) for intravenous epoprostenol compared with supportive care. The corresponding values for inhaled iloprost (FCIII PPH patients; licensed indication), bosentan, sitaxentan (FCIII patients with mixed PAH; licensed indication) and sildenafil (FCIII patients with mixed PAH; licensed indication) were 0.29 (95% CI 0.07-1.18), 0.21 (95% CI 0.03-1.76), 0.18 (95% CI 0.02-1.64) and [Commercial-in-confidence information has been removed] respectively. The incremental cost-effectiveness ratios (ICERs) for the technologies plus supportive care compared with supportive care alone, determined by independent economic evaluation, were 277,000 pounds/quality-adjusted life-year (QALY) for FCIII and 343,000 pounds/QALY for FCIV patients for epoprostenol, 101,000 pounds/QALY for iloprost, 27,000 pounds/QALY for bosentan and 25,000 pounds/QALY for sitaxentan. For the most part sildenafil plus supportive care was more effective and less costly than supportive care alone and therefore dominated supportive care. In the case of epoprostenol the ICERs were sensitive to the price of epoprostenol and for bosentan and sitaxentan the ICERs were sensitive to running the model over a shorter time horizon and with a lower cost of epoprostenol. Two RCTs directly compared the technologies against each other with no significant differences observed between the technologies. Combinations of technologies were investigated in four RCTs, with some showing conflicting results.
CONCLUSION(S)
All five technologies when added to supportive treatment and used at licensed dose(s) were more effective than supportive treatment alone in RCTs that included patients of mixed FC and types of PAH. Current evidence does not allow adequate comparisons between the technologies nor for the use of combinations of the technologies. Independent economic evaluation suggests that bosentan, sitaxentan and sildenafil may be cost-effective by standard thresholds and that iloprost and epoprostenol may not. If confirmed, the use of the most cost-effective treatment would result in a reduction in costs for the NHS. Long-term, double-blind RCTs of sufficient sample size that directly compare bosentan, sitaxentan and sildenafil, and evaluate outcomes including survival, quality of life, maintenance on treatment and impact on the use of resources for NHS and personal social services are needed.
Topics: Antihypertensive Agents; Bosentan; Cost-Benefit Analysis; Endothelin Receptor Antagonists; Epoprostenol; Humans; Hypertension, Pulmonary; Iloprost; Isoxazoles; Phosphodiesterase Inhibitors; Piperazines; Purines; Sildenafil Citrate; Sulfonamides; Sulfones; Thiophenes; United States; Vasodilator Agents
PubMed: 19863849
DOI: 10.3310/hta13490 -
Frontiers in Pharmacology 2020Three oral drugs (ambrisentan, bosentan, and sildenafil) have been widely used to treat patients with pulmonary arterial hypertension (PAH). 1) There are no studies that...
Combined Methods (Formal Adjusted Indirect Comparison, Meta-Analysis and Principal Component Analysis) Comparisons of the Safety and Efficacy of Ambrisentan, Bosentan, and Sildenafil in the Patients With Pulmonary Arterial Hypertension.
BACKGROUND
Three oral drugs (ambrisentan, bosentan, and sildenafil) have been widely used to treat patients with pulmonary arterial hypertension (PAH). 1) There are no studies that directly compare the safety and efficacy of these three drugs. Existing studies could not meet the physician's need to select the most beneficial drugs for patients. 2) Principal component analysis is mainly used for scale analysis and has not been reported in clinical field. 3) When the results of the indirect meta-analysis were not satisfactory, no new solutions have been proposed in existing meta-analysis studies.
METHODS
The overall process of this study is divided into 4 steps 1) literature search and data extraction; 2) principal component analysis; 3) common reference-based indirect comparison meta-analysis; 4) formal adjusted indirect comparison.
RESULTS
Nine randomized controlled trials (RCTs) experiments and eight long-term experiments were selected. The main influencing factors are mortality, 6-min walk distance (6MW), mean pulmonary arterial pressure (PAP), cardiac index (CI) by principal component analysis. There was no significant heterogeneity among the indirect meta-analysis of three drugs. But in the formal adjusted indirect comparison 1) the level of PAP of sildenafil group (60.5 ± 22.35, 220) was higher than that of the other three groups, placebo (53.5 ± 17.63, 507) (p < 0.001), ambrisentan (49.5 ± 15.08, 130) (p < 0.001), and bosentan (54.6 ± 118.41, 311) (p < 0.001); 2) the level of CI of sildenafil group (54 ± 18, 311) was higher than that of the other three groups, placebo (2.7 ± 1.09, 518) (p < 0.001), ambrisentan (2.5 ± 0.75, 130) (p < 0.001), and bosentan (2.5 ± 1.06, 333) (p < 0.001). In addition, sildenafil significantly improved the survival rate comparing with ambrisentan and bosentan.
CONCLUSIONS
The results of this study suggest that sildenafil might be more suitable for long-term treatment of PAH patients than ambrisentan and bosentan. In order to enable clinicians to draw conclusions more quickly and directly in the data-rich literature, we suggest the use of principal component analysis combined with formal adjusted indirect comparison to compare the efficacy and safety of drugs.
PubMed: 32308623
DOI: 10.3389/fphar.2020.00400 -
Canadian Respiratory Journal 2018Although many studies have reported on the cost-effectiveness of bosentan for treating pulmonary arterial hypertension (PAH), a systematic review of economic evaluations...
OBJECTIVES
Although many studies have reported on the cost-effectiveness of bosentan for treating pulmonary arterial hypertension (PAH), a systematic review of economic evaluations of bosentan is currently lacking. Objective evaluation of current pharmacoeconomic evidence can assist decision makers in determining the appropriate place in therapy of a new medication.
METHODS
Systematic literature searches were conducted in English-language databases (MEDLINE, EMBASE, EconLit databases, and the Cochrane Library) and Chinese-language databases (China National Knowledge Infrastructure, WanFang Data, and Chongqing VIP) to identify studies assessing the cost-effectiveness of bosentan for PAH treatments.
RESULTS
A total of 8 published studies were selected for inclusion. Among them were two studies comparing bosentan with epoprostenol and treprostinil. Both results indicated that bosentan was more cost-effective than epoprostenol, while the results of bosentan and treprostinil were not consistent. Four studies compared bosentan with other endothelin receptor antagonists, which indicated ambrisentan might be the drug of choice for its economic advantages and improved safety profile. Only two economic evaluations provided data to compare bosentan versus sildenafil, and the results favored the use of sildenafil in PAH patients. Four studies compared bosentan with conventional, supportive, or palliative therapy, and whether bosentan was cost-effective was uncertain.
CONCLUSIONS
Bosentan may represent a more cost-effective option compared with epoprostenol and conventional or palliative therapy. There was unanimous agreement that bosentan was not a cost-effective front-line therapy compared with sildenafil and other endothelin receptor antagonists. However, high-quality cost-effectiveness analyses that utilize long-term follow-up data and have no conflicts of interest are still needed.
Topics: Antihypertensive Agents; Bosentan; Cost-Benefit Analysis; Endothelin Receptor Antagonists; Epoprostenol; Humans; Hypertension, Pulmonary; Phenylpropionates; Pyridazines; Sildenafil Citrate; Vasodilator Agents
PubMed: 30581511
DOI: 10.1155/2018/1015239 -
Cureus Nov 2021Diabetic nephropathy is becoming a more predominant cause of end-stage renal disease, as the prevalence of diabetes mellitus worldwide is on the rise. In this systematic... (Review)
Review
Diabetic nephropathy is becoming a more predominant cause of end-stage renal disease, as the prevalence of diabetes mellitus worldwide is on the rise. In this systematic review, we aimed to define the role of endothelin receptor antagonists, in the prevention and treatment of diabetic nephropathy, in addition to determining their safety. For this review, PubMed, Google Scholar, and Cochrane Library databases, in addition to ClinicalTrials.gov, were searched for publications in the last 20 years. We included 14 studies, seven randomized control trials, and seven post hoc analyses in this paper. Atrasentan decreased albuminuria, reduced blood pressure, and improved lipid profiles with more manageable fluid overload-related adverse events than avosentan and bosentan. Overall, endothelin receptor antagonists, in combination with renin-angiotensin-aldosterone system inhibitors, effectively reduce albuminuria and prevent the progression of diabetic kidney disease. However, more extensive clinical trials still need to be conducted to confirm these relationships and to learn more about the specific factors affecting their efficacy in individual patients.
PubMed: 34909290
DOI: 10.7759/cureus.19325 -
Journal of Korean Medical Science Aug 2013Some patients with chronic obstructive pulmonary disease (COPD) have pulmonary hypertension (PH) that adversely affects survival. We performed a systematic review and... (Meta-Analysis)
Meta-Analysis Review
Some patients with chronic obstructive pulmonary disease (COPD) have pulmonary hypertension (PH) that adversely affects survival. We performed a systematic review and meta-analysis to assess whether PH-specific therapies have an effect for stable COPD. Data sources were Medline, EMBASE, Cochrane Central Register of Controlled Trials, Korea med and references from relevant publications. Randomized prospective trials that compared PH specific therapy in COPD for more than 6 weeks with placebo were included. The outcomes were the exercise capacity and adverse events. Four randomized controlled trials involving 109 subjects were included in the analysis. Two trials involved bosentan, one sildenafil and one beraprost. The studies varied in duration of treatment from 3 to 18 months. In a pooled analysis of four trials, exercise-capacity was not significantly improved with PH-specific treatment for COPD (risk ratio, -5.1; 95% CI, -13.0 to 2.8). COPD with overt PH significantly improved the exercise capacity (mean difference, 111.6; 95% CI, 63.3 to 159.9) but COPD with PH unknown did not (mean difference, 26.6; 95% CI, -24.3 to 77.5). There was no significant difference in hypoxemia (mean difference, 2.6; 95% CI, -3.7 to 8.8). PH specific treatments have a significant effect in improving exercise capacity in COPD with overt PH.
Topics: Antihypertensive Agents; Bosentan; Clinical Trials as Topic; Databases, Factual; Epoprostenol; Humans; Hypertension, Pulmonary; Hypoxia; Piperazines; Pulmonary Disease, Chronic Obstructive; Purines; Risk Factors; Sildenafil Citrate; Sulfonamides; Sulfones; Surveys and Questionnaires
PubMed: 23960448
DOI: 10.3346/jkms.2013.28.8.1200