Efficacy and Safety of Pulmonary Arterial Hypertension-specific Therapy in Pulmonary Arterial Hypertension

Liu, Huan-long; Chen, Xueyan; Li, Jie-Ru; Su, Suwen; Ding, Tao; Shi, Chenxia; Yunfa, Jiang; Zhu, Zhongning

doi:10.1016/j.chest.2016.03.031

Cited by 49 publications

(49 citation statements)

References 47 publications

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“…Future comparative efficacy trials are, therefore, warranted to make definitive conclusions. Third, similar to previous PAH meta-analyses, 4,7,60,61 our analysis is somewhat limited by the small number of RCTs available for each drug; we had to combine the effect of multiple agents in a drug class. It is possible that the efficacy of agents is drug specific rather than class specific.…”

Section: Discussionmentioning

confidence: 99%

“…58,59 However, the direct meta-analyses in the published literature synthesized evidence informing about either the pooled effect of drug therapy on relevant outcomes 4,7 or the effect of combination vs monotherapy as a whole without addressing the role of individual agents. 60,61 They do not provide composite evidence incorporating all available data to assess the comparative effectiveness of different drug therapies in improving specific outcomes. By synthesizing evidence from existing trials to analyze both direct and indirect treatment comparisons, our network meta-analysis provides comprehensive evidence in which therapyspecific relative risks are comparable across classes.…”

Section: Discussionmentioning

confidence: 99%

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Comparative Effectiveness of Pharmacologic Interventions for Pulmonary Arterial Hypertension

Jain

Khera

Girotra

et al. 2017

Chest

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BACKGROUND:We conducted a systematic review and network meta-analysis to examine comparative efficacy and tolerability of pharmacologic interventions for pulmonary arterial hypertension (PAH).METHODS: MEDLINE, the Cochrane Register, EMBASE, CINAHL, and clinicaltrials.gov were searched (January 1, 1990 to March 3, 2016. Randomized controlled trials (RCTs) studying the approved pharmacologic agents endothelin receptor antagonists (ERA), phosphodiesterase inhibitors (PDE5i), the oral/inhaled (PO/INH) and IV/subcutaneous (SC) prostanoids, and riociguat and selexipag, alone or in combination, for pulmonary arterial hypertension (PAH) and reporting at least one efficacy outcome were selected.RESULTS: Thirty-one RCTs with 6,565 patients were selected. In network meta-analysis, when compared with a median placebo rate of 14.5%, clinical worsening was estimated at 2.8% with riociguat (risk ratio [RR], 0.19; 95% CI, 0.05-0.76); at 3.9% with ERA þ PDE5i (RR, 0.27; 95% CI, 0.14-0.52), and at 5.7% with PDE5i (RR, 0.39; 95% CI, 0.24-0.62). For improvement in functional status, when compared with 16.2% in the placebo group, improvement in at least one New York Heart Association/World Health Organization (NYHA/WHO) functional class was estimated at 81.8% with IV/SC prostanoids (RR, 5.06; 95% CI, 2.3211.04), at 28.3% with ERA þ PDE5i (RR, 1.75; 95% CI, 1.05-2.92), and at 25.2% with ERA (RR, 1.56; 95% CI, 1.22-2.00). Differences in mortality were not significant. Adverse events leading to discontinuation of therapy were highest with the PO/INH prostanoids (RR, 2.92; 95% CI, 1.68-5.06) and selexipag (RR, 2.06; 95% CI, 1.04-3.88) compared with placebo.CONCLUSIONS: Currently approved pharmacologic agents have varying effects on morbidity and functional status in patients with PAH. Future comparative effectiveness trials are warranted with a focus on a patient-centered approach to therapy. REGISTRATION: PROSPERO CRD42016036803CHEST 2017; 151(1):90-105 KEY WORDS: comparative efficacy; network meta-analysis; pulmonary arterial hypertension ABBREVIATIONS: 6MWD = 6-min walk distance; ERA = endothelin receptor antagonist; FDA = Food and Drug Administration; GRADE = Grading of Recommendations Assessment, Development, and Education; NYHA = New York Heart Association; PAH = pulmonary arterial hypertension; PDE5i = phosphodiesterase-5 inhibitor; RCT = randomized controlled trial; RR = risk ratio; SUCRA = surface under the cumulative ranking area; WHO = World Health Organization; WMD = weighted mean difference Pulmonary arterial hypertension (PAH) or World Health Organization (WHO) group 1 pulmonary hypertension is a progressive disease associated with significant morbidity and a 5% to 15% annual mortality rate. [1][2][3] In recent years, a number of drug classes to treat PAH have been approved for clinical use. These include endothelin receptor antagonists (ERA), phosphodiesterase-5 inhibitors (PDE5i), parenteral and nonparenteral prostacyclins, a soluble guanylate cyclase stimulator, and a prostacyclin-receptor agonist. Although randomized ...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Comparative Effectiveness of Pharmacologic Interventions for Pulmonary Arterial Hypertension

Jain

Khera

Girotra

et al. 2017

Chest

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“…Этот факт был подтвержден в метаанализе Bai Y. и соавт., в котором было показано, что прирост Д6MХ в случае комбинированной терапии был гораздо меньше, чем в РКИ с применением монотерапии [14]. Тем не менее в этом метаанализе объединялись пациенты, получавшие монотерапию и комбинацию спец-ифических препаратов [14,16]. Включение в РКИ пациен-тов, ранее получавших ЛАГ-специфический препарат, снижает возможность продемонстрировать разницу между группой плацебо и группой активной терапии [8].…”

Section: рисунок 2 алгоритм лечения больных лаг [2]unclassified

“…оценивалась эффективность и безопасность специфической терапии у пациентов с ЛАГ, причем режимы монотерапии и комби-нированной терапии рассматривались отдельно [16]. В результате анализа 418 публикаций, посвященных этому аспекту, авторы исключили обзоры, абстракты, исследова-ния на животных, РКИ с перекрестным дизайном; при-менением ситакзентана, который был запрещен для кли-нического применения в 2010 г.; варденафила, который не одобрен для лечения пациентов с ЛАГ в Северной Америке и Европе.…”

Section: рисунок 2 алгоритм лечения больных лаг [2]unclassified

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Aspects of Modern Combination Specific Therapy of Pulmonary Arterial Hypertension: the Pros and Cons

Мартынюк¹,

Наконечников²,

Chazova³

2017

Med. sov.

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Berberine attenuates pulmonary arterial hypertension via protein phosphatase 2A signaling pathway both in vivo and in vitro

Luo

Liu

et al. 2018

Journal Cellular Physiology

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Excessive proliferation, migration, and antiapoptosis of pulmonary artery (PA) smooth muscle cells (PASMCs) underlies the development of pulmonary vascular remodeling. The innervation of the PA is predominantly sympathetic, and increased levels of circulating catecholamines have been detected in pulmonary arterial hypertension (PAH), suggesting that neurotransmitters released by sympathetic overactivation may play an essential role in PAH. However, the responsible mechanism remains unclear. Here, to investigate the effects of norepinephrine (NE) on PASMCs and the related mechanism, we used 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide, the proliferating cell nuclear antigen and the cell counting kit-8 assay to evaluate the proliferation of PASMCs, Boyden chamber migration, and wound-healing assays to assess migration and western blot analysis to investigate protein expression. We demonstrated that the phosphorylation level of the protein phosphatase 2A (PP2A) catalytic subunit (Y307) was higher in PAH patients and PAH models than in controls, both in vivo and in vitro. In addition, NE induced the proliferation and migration of PASMCs, which was attenuated by berberine (BBR), a Chinese herbal medicine, and/or PP2A overexpression. PP2A inhibition worsened NE-induced PAH and could not be reversed by BBR. Thus, PP2A is critical in driving PAH, and BBR may alleviate PAH via PP2A signaling pathways, thereby offering a potential therapeutic option for PAH.

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Efficacy and Safety of Pulmonary Arterial Hypertension-specific Therapy in Pulmonary Arterial Hypertension

Cited by 49 publications

References 47 publications

Comparative Effectiveness of Pharmacologic Interventions for Pulmonary Arterial Hypertension

Comparative Effectiveness of Pharmacologic Interventions for Pulmonary Arterial Hypertension

Aspects of Modern Combination Specific Therapy of Pulmonary Arterial Hypertension: the Pros and Cons

Berberine attenuates pulmonary arterial hypertension via protein phosphatase 2A signaling pathway both in vivo and in vitro

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