波生坦治疗特发性肺动脉高压的临床疗效

目的 探讨口服波生坦治疗特发性肺动脉高压( IPAH)的临床效果.方法 将45例特发性肺动脉高压患者随机分为治疗组23例和对照组22例;两组均采取常规治疗,治疗组在此基础上口服波生坦;根据观察结果,分析、探讨两组的治疗效果.结果 经过14d治疗,治疗组PaO2和6MWD分别为(81.0±3.7)mm Hg(1 mm Hg=0.133 kPa)和(331.0±81.2)m,较对照组的(57.0±3.9) mmHg和(263.0±58.9)m高;PaCO2、PAP分别为(43.0±5.9) mm Hg和(63.0±17.1) mm Hg,较对照组的(66.0±7.2) mm Hg和(78.0±16.7)mm Hg低;两组比较差异均有显著性(P＜0.05).结论 口服波生坦能有效治疗特发性肺动脉高压,显著降低肺动脉压.     

波生坦治疗特发性肺动脉高压的临床研究

目的观察波生坦治疗特发性肺动脉高压的临床疗效及安全性。方法选择我院收治的15例特发性肺动脉高压患者,口服波生坦进行治疗,对比治疗前后患者的各项指标变化情况。结果治疗后,患者心功能得到了明显改善;6WMD、NT-proBNP、LVEDD、mPAP等指标均较治疗前明显改善(P<0.05);患者血常规及肝肾功能检查结果均无明显变化(P>0.05)。结论波生坦是治疗特发性动脉高血压的安全有效的药物,值得向临床推荐。     

波生坦治疗CTD肺动脉高压

波生坦治疗3个月通过重建内皮功能对肺动脉高压有治疗益处，使内皮细胞血浆标志物活性降低，从而可以稳定或改善严重肺动脉高压。     

波生坦治疗肺动脉高压的临床疗效评价

肺动脉高压(PAH)是一严重的进行性肺部疾病。近来研究表明,内皮素(ET)水平的升高与PAH严重程度密切相关。因此,ET受体拮抗剂极有希望成为治疗PAH的新途径。波生坦(bosentan)在原发性PAH或硬皮病引起的PAH治疗中显现出较好的疗效。随着临床应用的推广,其长期临床疗效和安全性越来越受到重视。     

波生坦联合西地那非治疗肺动脉高压的临床效果

目的 观察波生坦联合西地那非治疗肺动脉高压的临床效果。方法 选取2021年1月—2022年1月厦门市第五医院收治的肺动脉高压患者86例,以随机数字表法分为波生坦联合组(n=43)与西地那非组(n=43)。西地那非组给予西地那非治疗,波生坦联合组在西地那非组基础上给予波生坦治疗,2组均连续用药3个月。比较2组患者疗效、6 min步行距离、Brog呼吸困难指数、左室舒张末期内径(LVEDD)、左室收缩末期内径(LVESD)、左室射血分数(LVEF)及不良反应。结果 波生坦联合组总有效率为93.02%,高于西地那非组的74.42%(χ²=5.460,P=0.019)。治疗3个月后,2组6 min步行距离较治疗前延长,Brog呼吸困难指数较治疗前降低,且波生坦联合组变化幅度大于西地那非组(P<0.05或P<0.01);2组LVEDD、LVESD较治疗前缩短,LVEF较治疗前升高,且波生坦联合组变化幅度大于西地那非组(P<0.05或P<0.01)。波生坦联合组与西地那非组不良反应总发生率比较差异不显著(6.98%vs. 4.65%,P=1.000)。...     

波生坦治疗儿童肺动脉高压疗效的影响因素分析

[摘要]目的：探讨波生坦治疗儿童肺动脉高压疗效的影响因素。方法：选取2013年6月至2016年6月在我院诊断为肺动脉高压且接受波生坦治疗的患儿68例,定期随访,以患儿死亡或行肺移植治疗为随访终点,收集患儿的临床资料,包括年龄、性别、身体质量指数（BMI）、病史、体格检查及治疗后血常规、心导管检查结果,对相关指标进行单因素及多因素分析,评价各种因素与波生坦治疗小儿肺动脉高压疗效的相关性。结果：患儿的年龄、水肿及纽约心脏病协会（NYHA）心功能分级、肌钙蛋白I（TnI）、血红蛋白（HGB）、总胆红素（TBIL）、肺小动脉阻力指数（PVRI）等因素与波生坦治疗儿童肺动脉高压的临床效果相关（P<0.05）。进一步多因素Logistic回归分析显示,年龄<5岁、NYHA心功能分级为Ⅲ~Ⅳ级、TBIL≥6.23 µmol/L是波生坦治疗儿童肺动脉高压疗效不佳（发生终点事件）的独立危险因素（P<0.05）。结论：影响波生坦治疗儿童肺动脉高压疗效的因素较多,临床应针对性干预。     

波生坦联合西地那非治疗肺动脉高压的Meta分析

目的系统评价在治疗单一药物控制不佳的肺动脉高压方面波生坦和西地那非联合使用在临床的疗效,为临床用药提供循证方面的参考。方法计算机检索维普(VIP)、万方(Wangfang data)、中国知网(CNKI)、Medline、PubMed、Embase、Cochrane图书馆和CBM。检索时间从建库至2019年4月1日。收集波生坦联合西地那非(观察组)对比其他两种药物联合组(对照组)治疗肺动脉高压疗效的文献。疗效指标包括:肺动脉压力、6分钟步行距离、呼吸困难指数。根据纳入和排除的标准,利用EndNote软件进行文献筛查,资料提取,并使用RevMan5. 3软件进行数据处理。结果最终纳入24项研究,共3114例患者,对照组和观察组的Meta分析结果显示波生坦联合西地那非(观察组)在改善肺动脉压力(WMD=-4. 65 mmHg,95%CI:-7. 52^-1. 78,P=0. 002)、降低呼吸困难指数(WMD=-0. 56,95%CI:-0. 83^-0. 29,P<0. 001)、提高6分钟步行距离(WMD=30. 08 m,95%CI:17. 26~42. 90,P<0. 001)方面均优于其他两种药物联合组(对照组)。结论波生坦联合西地那非治疗肺动脉高压效果显著。     

波生坦对儿童先天性心脏病相关肺动脉高压的治疗作用

目的 观察波生坦在儿童先天性心脏病(CHD)相关肺动脉高压(PAH)患儿中应用的疗效及安全性,评价波生坦治疗儿童CHD-PAH的临床效果.方法 入选2008年1月至2011年5月首都医科大学附属北京安贞医院小儿心脏科入院≤18岁CHD-PAH患儿23例,给予波生坦口服治疗,进行开放性、观察性研究.随访评估服药前后6 min步行试验距离(6MWTD)、经皮血氧饱和度(SpO2)、纽约心脏病学会心功能分级(NYHA-FC)、心导管检查血流动力学参数(平均肺动脉压、肺小动脉阻力指数、肺体循环流量比、肺体循环阻力比)及肝功能变化.结果入选儿童患儿23例,平均年龄为(9.1±3.6)岁(2.1～14.7岁).口服波生坦治疗平均时间(13.3±7.5)个月(6 ～31个月).治疗后,11例患儿(年龄7岁以上)的6MWTD从(458±16)m增加至(496±49)m(P =0.035).23例患儿的SpO2 (89 ±6)％提高到(91±5)％(P=0.009).此外,所有患儿的NYHA心功能分级有不同程度改善或保持稳定.12例服药后再次接受心导管检查的患儿,肺、体循环比( Qp/Qs)由服药前平均(0.97 ±0.38)增至(1.16±0.39)(P =0.076),平均肺动脉压(mPAP)由(76±6)mm Hg(1 mm Hg=0.133 kPa)增至(78±12)mm Hg(P =0.649),肺小动脉阻力指数( PVRi)由平均(20.78±8.84) Woods units/m2降至( 18.13±7.71) Woods units/m2(P=0.165),肺、体循环阻力比(Rp/Rs)由(1.03±0.38)降至(0.83±0.29)(P=0.06),以上指标均有不同程度改善,但差异无统计学意义.所有患儿均对波生坦良好耐受,仅1例10岁男性患儿有一过性鲜血便.结论 服用波生坦可明显改善CHD-PAH患儿的6MWT、SpO2、NYHA-FC,降低PVR及Rp/Rs.波生坦在不符合手术适应证的儿童CHD-PAH患儿中的应用是安全、有效的.     

贝前列素联合波生坦对中重度肺动脉高压的疗效观察

目的 观察贝前列素联合波生坦对中重度肺动脉高压（PH）的疗效.方法 30例中重度PH患者采用常规治疗及波生坦治疗,观察组在此基础上加用贝前列素钠,观察用药前后患者肺动脉收缩压（SPAP）、肺动脉平均压（mPAP）及肺动脉舒张压（DPAP）并进行统计学比较.结果 贝前列素与波生坦联用可较单独应用波生坦更有效地改善肺动脉压,两药联合治疗组SPAP和mPAP均显著降低,且两种治疗方案的不良反应发生率低.结论 贝前列素与波生坦联合治疗可能是PH安全有效的治疗方案.     

波生坦治疗新生儿缺氧性肺动脉高压的临床观察

目的:观察波生坦治疗新生儿缺氧性肺动脉高压(HPH)的有效性和安全性。方法:选择2014年1月-2019年3月于我院新生儿科住院治疗的82例HPH新生儿为研究对象,按是否加用波生坦治疗分为波生坦组(50例)和非波生坦组(32例);另选取25例血清标本留取时间、出生胎龄、日龄等一般资料与波生坦组匹配的非HPH新生儿为对照组。所有HPH新生儿均给予持续静脉滴注盐酸多巴胺注射液5 mg/(kg·min),直到肺动脉收缩压(PASP)正常;在此基础上,波生坦组患儿加用波生坦片1 mg/kg(用适量注射用水溶解后喂服),q12 h,连用72 h。分析HPH患儿血清内皮素1(ET-1)水平与PASP的关系,并比较治疗前后波生坦组和非波生坦组HPH患儿的PASP和疗效以及3组患儿的动脉血气指标变化及不良反应发生情况。结果:治疗前,波生坦组患儿血清ET-1水平为(164.3±115.3)pg/mL,显著高于对照组的(41.9±3.7)pg/mL,且与PASP呈正相关(r=0.864,P<0.001)。波生坦组患儿的治疗总有效率为90.00%,显著高于非波生坦组的71.88%(P<0.05)...     

Pharmacokinetics of bosentan in routinely treated Japanese pediatric patients with pulmonary arterial hypertension

We evaluated the pharmacokinetics of routinely administered bosentan in 46 Japanese pediatric patients with pulmonary arterial hypertension. Plasma samples were taken twice at times corresponding to the peak and trough concentrations following repetitive oral administration. The population pharmacokinetic parameters of bosentan were estimated by use of the NONMEM program, in which a one-compartment model with repetitive bolus dosing was parameterized in terms of the oral clearance (CL/F) and elimination rate constant (k). Polymorphisms of CYP3A5, SLCO1B1, SLCO1B3, and SLCO2B1 had no significant effect on the disposition of bosentan. In addition, the pharmacokinetics of bosentan was not altered by heart failure or coadministration of sildenafil. In contrast, weight (WT)-normalized values of CL/F were correlated negatively with age (AGE). The final population mean values of CL/F and k were estimated to be 0.409 · (1 - 0.0377 · (AGE - 3.81)) · WT L/h and 0.175 h(-1), respectively.     

肺动脉高压药物及新靶点研究进展

肺动脉高压(PAH)为一种少见的慢性疾病,其危害性大、致死率高,多发于老年人和妇女。随着我国步入老龄化社会,对PAH的防治越发重视。综述了包括CCBs、PDE-5抑制剂、ERAs和PGI2类常规靶点和鸟苷酸环化酶激动剂,5-羟色胺,Bcr-Abl蛋白络氨酸激酶抑制剂,Rho-激酶抑制剂,内皮祖细胞和基因等治疗该疾病的新型作用靶点在内的最新靶点与药物的研究进展,以及新一代药物的发展方向。     

波生坦治疗中重度特发性及先天性心脏病相关肺动脉高压40例

目的观察波生坦一线治疗先天性心脏病相关肺动脉高压(CHD-PAH)和特发性肺动脉高压(IPAH)患者疗效和用药前后生活质量(QOL)改善情况。方法 40例住院经右心导管检查确诊为CHDPAH和IPAH的患者给予波生坦62.5 mg,bid,4周后调整为125 mg,bid。比较用药前、3个月时患者QOL各维度的改善情况,分别记录并比较治疗前、治疗后1个月和3个月时患者的6 min步行距离(6MWD)、WHO心功能、Borg呼吸困难指数和超声心动图结果。结果波生坦能有效地提高患者QOL的生理机能、生理职能、躯体疼痛、一般状况、精力、情感职能和精神健康7个维度(P<0.01)。对CHDPAH和IPAH两个亚组分别进行比较,除社会功能外,治疗前后其他维度均有显著改善(P<0.01),且两亚组间均无显著差异(P>0.05)。治疗1个月后,患者的6MWD增至(393.1±63.4)m,治疗3个月后为(425.6±68.9)m,与治疗前(351.9±70.9)m相比均有非常显著差异(P<0.01)。治疗3个月后,26例(65%)患者WHO心功能降低1级,4例(10%)降低2级,10例患者维持原有分级不变;患者的肺血管收缩压明显改善,由治疗前(110.6±24.1)mmHg下降为(99.5±26.3)mmHg(P=0.011);对主要指标6MWD、Borg呼吸困难指数和心超指标等进行CHD-PAH和IPAH两亚组组间分析,除左室收缩末内径外,均无显著差异(P>0.05);总体患者的不良反应发生率低。结论波生坦短期治疗CHD-PAH和IPAH患者的疗效确定、结果相近,均可提高其运动能力、明显改善生活质量的7个维度,缓解呼吸困难的症状,且安全性、耐受性良好。     

Long-term trial of bosentan monotherapy for pulmonary arterial hypertension in Japanese patients

ABSTRACT

Objective: To determine the efficacy and safety of long-term bosentan monotherapy in Japanese patients with pulmonary arterial hypertension (PAH).

Research design and methods: The present study was an extension to a 12?week open-label trial of bosentan in which 21 Japanese patients with PAH received bosentan, 125?mg twice daily. Of the 21 patients in the initial trial, 20 elected to participate in the long-term study and to continue to receive bosentan for up to 3 years.

Main outcome measures: The primary efficacy measure was comparison of World Health Organization (WHO) functional class for pulmonary arterial hypertension following long-term (> 2.5 years) therapy compared with baseline (prior to initiation of bosentan). Secondary outcomes included time from initiation of bosentan therapy to clinical worsening and safety assessments.

Results: Bosentan treatment was continued for a median of 2.7 years (range 0.4–3.0 years); 12 patients received bosentan monotherapy for at least 2.5 years. Following long-term treatment, improvement of WHO functional class compared with baseline was observed in 9/12 patients (75.0%) and in 3/12 patients (25.0%) the functional class remained stable; no patient experienced a worsening of WHO functional class compared with baseline. Overall, long-term treatment with bosentan was well tolerated.

Conclusions: Long-term treatment with bosentan is well tolerated and is associated with sustained clinical improvement in Japanese patients with PAH. Bosentan, therefore, represents a valuable treatment option for Japanese patients with this devastating disease.     

Effect of bosentan treatment on surrogate markers in pulmonary arterial hypertension

OBJECTIVE: The aim of this study was to evaluate the effect of the oral dual ET(A)/ET(B) receptor antagonist bosentan on different surrogate markers in patients with pulmonary arterial hypertension (PAH). DESIGN AND SETTING: Prospective, open label, uncontrolled study in a University Hospital in Brazil. POPULATION: Fifteen PAH patients (11 females) with mean age of 40 +/- 11 years (5 in WHO functional class II, 10 in class III). METHODS: All patients were investigated at baseline and after 16 weeks of bosentan treatment. We used the following surrogate markers for patients' evaluation: 6-min walk test, quality of life questionnaire (Short Form SF-36) and N-terminal proBNP (B type natriuretic peptide) fraction levels in blood. RESULTS: Between the evaluation at baseline and week 16, the 6-min walk test distance changed from 396 +/- 135 to 434 +/- 137 m (p < 0.05). Each of the eight domains of the SF-36 was significantly improved. Mean NT-proBNP levels were decreased from a mean of 1670 pg/mL to 1010 pg/mL (p = 0.01). CONCLUSION: The study suggests that bosentan treatment results in the improvement of different kinds of surrogate markers independently of their specificity to reflect functional capacity, quality of life and myocardial stress. It is concluded that the combined use of these different markers may be an alternative endpoint for future short duration clinical trials.     

Effect of bosentan treatment on surrogate markers in pulmonary arterial hypertension

ABSTRACT

Objective: The aim of this study was to evaluate the effect of the oral dual ET_A/ET_B receptor antagonist bosentan on different surrogate markers in patients with pulmonary arterial hypertension (PAH).

Design and setting: Prospective, open label, uncontrolled study in a University Hospital in Brazil.

Population: Fifteen PAH patients (11 females) with mean age of 40 ± 11 years (5 in WHO functional class II, 10 in class III).

Methods: All patients were investigated at baseline and after 16 weeks of bosentan treatment. We used the following surrogate markers for patients’ evaluation: 6‐min walk test, quality of life questionnaire (Short Form SF‐36) and N‐terminal proBNP (B type natriuretic peptide) fraction levels in blood.

Results: Between the evaluation at baseline and week 16, the 6‐min walk test distance changed from 396 ± 135 to 434 ± 137?m (?p < 0.05). Each of the eight domains of the SF‐36 was significantly improved. Mean NT‐proBNP levels were decreased from a mean of 1670?pg/mL to 1010?pg/mL (?p = 0.01).

Conclusion: The study suggests that bosentan treatment results in the improvement of different kinds of surrogate markers independently of their specificity to reflect functional capacity, quality of life and myocardial stress. It is concluded that the combined use of these different markers may be an alternative endpoint for future short duration clinical trials.     

Treatment of pulmonary arterial hypertension with bosentan: from pathophysiology to clinical evidence

In addition to its potent vasoconstricting effect, endothelin (ET)-1 induces proliferation of pulmonary vascular cells and appears to play a pathogenic role in the development of pulmonary arterial hypertension (PAH). Blockade of the ET receptors has been proposed for the treatment of this condition. Bosentan (Tracleer^®, Actelion Pharmaceuticals), an oral ET_A/ET_B receptor antagonist, has been shown to improve exercise capacity, quality of life, haemodynamics and time to clinical worsening of patients with PAH in short-term placebo-controlled trials. These improvements were sustained, and a long-term observational study on idiopathic PAH patients suggested a favourable effect on survival in this subset. In the present report, the pharmacology, clinical efficacy and safety profile of bosentan are summarised. The place of bosentan among the current therapies available for the treatment of PAH is also discussed.     

Treatment of pulmonary arterial hypertension with bosentan: from pathophysiology to clinical evidence

In addition to its potent vasoconstricting effect, endothelin (ET)-1 induces proliferation of pulmonary vascular cells and appears to play a pathogenic role in the development of pulmonary arterial hypertension (PAH). Blockade of the ET receptors has been proposed for the treatment of this condition. Bosentan (Tracleer, Actelion Pharmaceuticals), an oral ETA/ETB receptor antagonist, has been shown to improve exercise capacity, quality of life, haemodynamics and time to clinical worsening of patients with PAH in short-term placebo-controlled trials. These improvements were sustained, and a long-term observational study on idiopathic PAH patients suggested a favourable effect on survival in this subset. In the present report, the pharmacology, clinical efficacy and safety profile of bosentan are summarised. The place of bosentan among the current therapies available for the treatment of PAH is also discussed.