Treatment of Pulmonary Arterial Hypertension Using Initial Combination Therapy of Bosentan and Iloprost

Han, Xinpeng; Zhang, Yuhai; Dong, Liang; Fang, Liying; Chai, Yaqin; Niu, Mengjie; Yu, Yongsheng; Liu, Lingli; Yang, Xiangming; Qu, Shuoyao; Li, Shengqing

doi:10.4187/respcare.05280

Cited by 16 publications

(12 citation statements)

References 25 publications

(26 reference statements)

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“…The New York Heart Association (NYHA) and the World Health Organization (WHO) functional classification systems were used to identify functional impairment in PAH. McLaughlin et al (33) and Hoeper et al (34) performed their studies using the NYHA functional classification, the remaining three studies were performed using the WHO functional classification (23,35,36). After meta-analysis, the result showed that there was significant heterogeneity (I 2 =73%; P=0.02) in WHO functional class improvement I between bosentan combination therapy and bosentan monotherapy (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Two of the five trial studies reported the effects of bosentan combination therapy on mean PAP (mPAP; Fig. 5) (33,35). The difference of mPAP demonstrated an average of only 11.95 mmHg (95% CI: −17.06, −6.83; P<0.00001) between bosentan combination therapy and monotherapy, and there was no heterogeneity between the groups (I 2 =6%; P=0.30).…”

Section: Resultsmentioning

confidence: 99%

“…One study did not include any data of clinical worsening (35) The clinical worsening rate in combination therapy was 5.5% (8/145) compared with that of monotherapy of 10.5% (16/152). The heterogeneity between the groups was found to be non-significant (I 2 =13%; P=0.33).…”

Section: Resultsmentioning

confidence: 99%

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A meta‑analysis of the safety and efficacy of bosentan therapy combined with prostacyclin analogues or phosphodiesterase type‑5 inhibitors for pulmonary arterial hypertension

Dang

Tang²,

et al. 2019

Exp Ther Med

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Bosentan is an effective drug for the treatment of pulmonary arterial hypertension (PAH). The aim of the present meta-analysis was to examine the evidence concerning the efficacy and safety of bosentan therapy combined with prostacyclin analogues or phosphodiesterase type 5 (PDE-5) inhibitors for treating PAH. Eligible published studies were collected from Embase, PubMed, The Cochrane Library and the website. Heterogeneity was assessed using the Cochran Q-statistic test. Results were presented as risk ratios or mean differences with 95% confidence intervals (CI). A total of five studies, comprising 310 patients were included for analysis. No significant improvements in six-minute walk distance (6MWD; mean difference, 16.43 m), clinical worsening (risk ratio, 0.54) and the World Health Organization functional classification (class I: risk ratio, 1.17; class II: risk ratio, 1.18) were observed in patients treated with bosentan in combination with prostacyclin analogues or PDE-5 inhibitors. However, a significant reduction in the mean pulmonary artery pressure (mPAP; 95% CI: −17.06, −6.83; P<0.0001) following bosentan combination therapy was observed. Comparisons of adverse event rates in the bosentan combination therapy (55.6%) and monotherapy (51.8%) suggested that there is no reduction in adverse events (risk ratio, 1.10). The results indicated that bosentan combined with prostacyclin analogues or PDE-5 inhibitors may not improve 6MWD, cardiac function, clinical worsening and adverse events. However, bosentan combined with prostacyclin analogues or PDE-5 inhibitor therapy was able to significantly reduce mPAP compared with the effect of bosentan monotherapy.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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A meta‑analysis of the safety and efficacy of bosentan therapy combined with prostacyclin analogues or phosphodiesterase type‑5 inhibitors for pulmonary arterial hypertension

Dang

Tang²,

et al. 2019

Exp Ther Med

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“…For the initial combination therapy, it was confirmed for the first time that the WHO FC II–III PAH patients received combination therapy more benefits in the Research of AMBITION in 2015 (Galiè et al, 2015 ). Since then, more and more evidence, including large RCTs, supports initial combination therapy as an effective treatment strategy for PAH (Hassoun et al, 2015 ; Han et al, 2017 ; D’Alto et al, 2018 ). Therefore, the 2018 WORLD SYMPOSIUM ON PULMONARY HYPERTENSION (WSPH) emphasized the importance of combination therapy for PAH patients and recommended low/intermediate/high-risk PAH patients with negative acute vascular reactivity test should first consider the combination of ERA and PDE5i (Qin and Zhi-Hong, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

Efficacy and safety of novel-targeted drugs in the treatment of pulmonary arterial hypertension: a Bayesian network meta-analysis

et al. 2021

Drug Delivery

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Background: Pulmonary arterial hypertension (PAH) is a severe and fatal clinical syndrome characterized by high blood pressure and vascular remodeling in the pulmonary arterioles, which is also a rapidly progressing disease of the lung vasculature with a poor prognosis. Although PAH medication made great advances in recent years, the efficacy and safety of the medication are unsatisfactory. Therefore, we aimed to update and expand previous studies to explore the efficacy and safety of PAH-targeted medications. Methods: Relevant articles were searched and selected from published or publicly available data in PubMed, Cochrane Library, CNKI, PsycInfo, and MEDLINE (from inception until October 1 st , 2020). To assess the efficacy and safety of PAH therapies, five efficacy outcomes [6-minute walking distance (6MWD), mean pulmonary arterial pressure (mPAP), WHO functional class (WHO FC) improvement, clinical worsening, death] and two safety outcomes [adverse events (AEs), serious adverse events (SAEs)] were selected. And 6MWD was regarded as the primary efficacy outcome. Results: 50 trials included with 10 996participants were selected. In terms of efficacy, all targeted drugs were more effective than placebo. For 6MWD, Bosentan + Sildenafil, Sildenafil, Bosentan + Iloprost were better than others. Bosentan + Iloprost and Bosentan + Sildenafil were better for mPAP. Bosentan + Iloprost and Ambrisentan + Tadalafil were more effective in improving WHO FC. Bosentan + Tadalafil and Bosentan + Iloprost had the Ambrisentan probability to reduce the incidence of clinical worsening. It is demonstrated that Ambrisentan had clear benefits in reducing all-cause mortality. In terms of safety, no therapies had been shown to reduce the incidence of SAEs significantly, and Ambrisentan + Tadalafil significantly increased the incidence of AEs. Conclusions: Phosphodiesterase 5 inhibitor (PDE5i) + Endothelin Receptor Antagonists (ERA) seems to be better therapy for PAH. Prostacyclin analogs (ProsA) + ERA appear promising, though additional data is warranted. Registration PROSPERO CRD42020218818.

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“…Еще [40,41]. В многоцентровом открытом РКИ III фазы X. Han и соавт., 2017 (n=27) [42] у больных ЛАГ III-IV ФК продемонстрировали, что стартовая комбинация бозентана и ингаляционного илопроста эффективнее увеличивала дистанцию 6МХ, улучшала показатели гемодинамики (среднее ДЛА, сердечный индекс), NT-proBNP, ФК и качество жизни по сравнению с монотерапией каждым из препаратов. Лекарственного взаимодействия между ингаляционным илопростом и бозентаном не отмечается [43].…”

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Advantages and limitations of initial combination therapy in pulmonary arterial hypertension patients in Russia

Шмальц

Горбачевский

2020

Terapevticheskii arkhiv

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Pulmonary arterial hypertension (PAH) is severe and often times rapidly progressive disease with fatal outcome. The concept of initial combination of PAH-specific therapies in high risk patients at baseline was first described in the European guidelines on pulmonary hypertension (PH) in 2009, and in low or intermediate risk patients at baseline in 2015. Interestingly, that in Cologne Experts Consensus, and then in the 6th World Symposium on PH medical community started considering initial combination therapy as one of the most important pillars in PAH treatment algorithms in 2018. As of August 2020, as many as 8 formulations of 7 reference PAH-specific drugs are licensed for medical use in the Russian Federation. On top of that, 6 abbreviated drugs (generics) have also become available few years ago. Unfortunately, intravenous and subcutaneous prostacyclin analogs (PCA) and tadalafil are not approved for PH patients treatment in the Russian Federation. In this narrative review paper we attempted to describe studies on initial dual combination therapy with PAH-specific drugs registered in Russia, i.e. ambrisentan and riociguat, macitentan and riociguat, macitentan and sildenafil in low or intermediate risk patients at baseline, as well as iloprost inhaled and sildenafil, iloprost inhaled and bosentan in high risk patients. Some beneficial pharmacological effects due to the synergy between ambrisentan plus riociguat, and inhaled iloprost plus sildenafil appear to be interesting and require further clinical confirmation. Other initial combinations of PAH-specific agents require large-scale clinical trials as well.

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Treatment of Pulmonary Arterial Hypertension Using Initial Combination Therapy of Bosentan and Iloprost

Cited by 16 publications

References 25 publications

A meta‑analysis of the safety and efficacy of bosentan therapy combined with prostacyclin analogues or phosphodiesterase type‑5 inhibitors for pulmonary arterial hypertension

A meta‑analysis of the safety and efficacy of bosentan therapy combined with prostacyclin analogues or phosphodiesterase type‑5 inhibitors for pulmonary arterial hypertension

Efficacy and safety of novel-targeted drugs in the treatment of pulmonary arterial hypertension: a Bayesian network meta-analysis

Advantages and limitations of initial combination therapy in pulmonary arterial hypertension patients in Russia

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