高原地区前列地尔治疗肺原性心脏病肺动脉高压的疗效观察

目的观察高原地区前列地尔（哈药集团,曼新妥）治疗肺心病肺动脉高压患者的疗效。方法将60例肺心病患者随机分为对照组和治疗组,每组30例。对照组为常规治疗;治疗组给予前列地尔注射液（曼新妥）10μg静脉注射,1次／d,共14d;观察治疗前后2组及组间肺动脉压力的变化。结果治疗组肺动脉压力显著降低,与对照组比较差异有统计学意义（P〈0．05）。结论高原地区应用前列地尔（曼新妥）治疗肺心病肺动脉高压能显著降低肺动脉压力,使用方便安全。     

前列地尔治疗肺心病肺动脉高压的临床效果观察

目的 观察前列地尔治疗肺心病肺动脉高压临床效果.方法 选择2006年1月至2010年12月180肺心病急性加重期伴肺动脉高压患者作为研究对象,随机分为观察组及对照组各90例.对照组吸氧、化痰止咳、抗感染、纠正水和电解质平衡、纠正心衰等常规治疗:观察组在对照组的基础上前列地尔10μg加入5％葡萄糖注射液250mL中静滴,每日1次,14天为1疗程.结果 两组治疗前SPAP、MAP、DPAP、PaO2、PaCO2比较无统计学差异(P＞0.05),治疗一疗程后观察组SPAP、MAP、DPAP、PaCO2低于对照组(P＜ 0.05); PaO2高于对照组(P＜0.05).观察组静滴前列地尔静脉区均有不同程度的灼热感,能忍受,输注完毕30min左右自动消失,均未发生头痛、皮疹、食欲减退、腹泻、低血压、心动过速等不良反应.结论 前列地尔联合应用治疗肺动脉高压,临床疗效显著,不良反应轻微,值得临床应用.     

前列地尔对慢性肺源性心脏病肺动脉高压疗效的临床研究

目的探讨前列地尔用于治疗慢性肺源性心脏病肺动脉高压的临床疗效,分析该药物的临床应用价值。方法选择2014年10月~2016年10月期间在我院就诊的84例慢性肺源性心脏合并肺动脉高压患者,随机分为两组,其中对照组采用一般的治疗方案,而观察组则是一般治疗+前列地尔联合治疗,对比两组患者治疗后的肺动脉收缩压(SPAP)、肺动脉平均压(MPAP)、肺动脉舒张压(DPAP)、动脉血氧分压(PaO_2)、动脉二氧化碳分压(PaCO_2)、FEV1和FEV1/FVC。结果两组患者在治疗后SPAP、DPAP、MPAP较之治疗前均有明显下降,差异有统计学意义(P<0.05),而其中以观察组患者的下降程度更具优势(P<0.05);治疗后两组患者的PaO_2、FEV1和FEV1/FVC相比治疗前均有了较为明显的提高,PaCO_2均有显著的下降差异有统计学意义(P<0.05),并且是观察组患者的肺功能指标改善更具有优势(P<0.05)。结论治疗慢性肺源性心脏病并肺动脉高压的患者,如果能够在常规治疗的方案外辅以前列地尔的治疗,能够进一步的提高原有疗效,显著改善患者肺功能和降低肺动脉压。     

前列地尔治疗先天性心脏病并肺动脉高压的疗效观察

目的观察前列地尔（PGE1）对先天性心脏病（CHD）合并肺动脉高压（PH）的血流动力学的影响。方法对36例先天性心脏病合并肺动脉高压患儿,用前列地尔治疗。静脉持续泵入量5ng/（kg·min）,平均用药（6.8±1.4）d。结果用药后临床症状、肺动脉压、氧合指数、右心射血分数有不同程度的改善。结论先天性心脏病（CHD）合并肺动脉高压（PH）的患儿,应用前列地尔治疗后,可使肺动脉压及肺循环阻力降低,提高动脉氧分压和氧饱和度,提高氧合指数,改善心肺功能。患者顺利脱离呼吸机,痊愈出院。     

前列地尔注射液治疗心脏病患者体外循环术后肺动脉高压的疗效观察

目的:观察前列地尔注射液对心脏病患者体外循环(CPB)术后肺动脉高压的治疗效果。方法:筛选出42例CPB术后合并肺动脉高压的心脏病患者,经中心静脉置管以20～40 ng.kg-1.min-1的速度泵入前列地尔注射液,比较用药前和用药后15、30、60 min患者的平均肺动脉压(mPAP)、平均动脉压(mSAP)、平均肺动脉压与动脉压之比(PP/PS)、心脏指数(CI)、肺血管阻力指数(PVRI)、体循环血管阻力指数(SVRI)等指标的变化。结果:患者用药后各时点的mPAP、PP/PS均较药前有显著降低(P均<0.01);患者用药后各时点的PVRI较用药前均有显著降低(P均<0.01),且呈逐渐下降趋势;CI在用药后各时点较用药前均有明显增高(P<0.05);mSAP、SVRI无显著变化(P>0.05)。结论:CPB术后应用前列地尔注射液,能有效降低肺动脉压、减轻右心负荷、增加心排量、维持血流动力学稳定,可增加手术安全性。     

前列地尔治疗肺尘埃沉着病合并肺源性心脏病肺动脉高压的临床应用

目的探讨肺尘埃沉着病合并肺源性心脏病肺动脉高压应用前列地尔治疗的疗效。方法对76例肺尘埃沉着病合并肺源性心脏病肺动脉高压患者随机分为对照组和治疗组,每组38例。对照组:给予持续性低流量吸氧,抗感染,祛痰、止咳平喘、强心利尿等改善心肺功能等常规治疗;治疗组:在常规治疗的基础上加用前列地尔注射液。结果治疗后SPAP、MPAP、DPAP和Pa CO2较治疗前显著降低,Pa O2、Sa O2、FEV1和FEV1/FVC较治疗前明显升高。对照组相比有显著差异(P<0.05)。结论前列地尔注射液治疗肺尘埃沉着病合并肺源性心脏病肺动脉高压疗效显著。     

前列地尔治疗维持性血液透析患者肺动脉高压的临床观察

目的探讨前列地尔治疗维持性血液透析（MHD）患者肺动脉高压（PH）的临床疗效。方法将60例MHD并发PH患者随机分为治疗组和对照组各30例。对照组仅给予常规治疗,治疗组在常规治疗基础上于透析后给予前列地尔40μg治疗,共6个月。比较2组治疗前及治疗后3、6个月肺动脉收缩压（SPAP）、血氧分压（PaO2）的变化。结果治疗组治疗后3、6个月SPAP逐渐降低,PaO2则逐渐升高,且同一治疗周期SPAP低于对照组,PaO2高于对照组,差异均有统计学意义（P〈0.05）。结论前列地尔能显著降低MHD患者的PH,改善心功能,提高生活质量,使用方便、安全。     

前列地尔联合低分子肝素治疗肺心病肺动脉高压的疗效观察

目的观察前列地尔联合低分子肝素治疗肺心病肺动脉高压患者的疗效。方法将128例肺心病患者随机分为3个试验组和对照组：对照组38例,为常规治疗;低分子肝素组30例,给与低分子肝素钠0．4ml皮下注射,每日两次,共14d;前列地尔组30例,给与前列地尔注射液20μg静脉注射,1次/d,共14d;联合治疗组30例,同时给与低分子肝素钠0．4ml皮下注射2次/d及前列地尔20μg静脉注射1次／d,共14d。观察治疗前后各组及组间肺动脉压力的变化。结果各组治疗后较治疗前相比肺动脉压力均显著降低,但联合治疗组更为明显,差异有显著性（P〈0．01）。结论前列地尔联合低分子肝素治疗肺心病肺动脉高压患者能显著降低肺动脉压力,使用方便安全。     

前列地尔治疗新生儿持续肺动脉高压疗效观察

目的 观察前列地尔治疗新生儿持续肺动脉高压（PPHN）的临床效果.方法 45例PPHN患儿随机分为两组.A组23例,用前列地尔治疗,临床应用开始剂量为以20 ng/（kg·min）泵入,在4～12 h 内逐渐增加到60ng/（kg·min）并维持3～4 d.B组应用硫酸镁饱和量200 mg/kg,30 min内静脉点滴,然后以20～50 mg/（kg·h）维持量维持,一般使用2～3 d .结果 A、B两组治疗前后肺动脉收缩压（PASP）明显下降,PaO2、OI、及临床症状明显改善,差异有极显著性（ P〈0.01）,两组间治疗后各指标比较,差异无显著性（P均〉0.05）,但前列地尔对体循环压力影响不明显,而硫酸镁使体循环压力下降,（P均〈0.01）,对患者血流动力学影响较大.结论 前列地尔和硫酸镁均可使新生儿PASP下降,前列地尔能选择性扩张肺血管从而降低肺动脉压力,且对体循环影响较小,副作用小.     

前列地尔辅助治疗慢性肺源性心脏病疗效观察

目的：观察前列地尔脂微球载体制剂（Lipo PGE1）治疗慢性肺源性心脏病的临床疗效及对肺动脉压力的影响。方法：将68例慢性肺源性心脏病患者随机分为两组,治疗组35例,在给予常规吸氧,抗生素、支气管扩张剂等治疗基础上加用Lipo PGE120μg/d,共14 d;对照组33例,为常规治疗。观察治疗前后两组患者临床症状缓解情况,呼吸困难评分及肺动脉压力的变化。结果：治疗组与对照组临床缓解率分别为88.57%和66.67%,差异有显著性（P〈0.05）;治疗组及对照组呼吸困难评分,平均肺动脉压力均较治疗前下降,差异有显著性（P〈0.01）;治疗组下降水平较显著,与对照组比较差异有显著性（P〈0.05）;治疗组仅1例患者有轻微头疼,停药后症状消失。结论：前列地尔脂微球载体制剂可改善慢性肺源性心脏病患者临床症状,同时能显著降低肺动脉压力,使用方便安全。     

Sildenafil: a review of its use in pulmonary arterial hypertension

Sildenafil citrate (Revatio), an inhibitor of phosphodiesterase type 5 (PDE5), is approved for use in the US, Europe and other countries for the treatment of pulmonary arterial hypertension (PAH). Oral sildenafil 20 mg three times daily added to conventional background therapy was significantly more effective than placebo at increasing exercise capacity in patients with idiopathic PAH or PAH associated with connective tissue diseases or repaired congenital systemic-to-pulmonary shunts. Sildenafil was also associated with improvements in WHO functional class and haemodynamic parameters, and was generally well tolerated. Sildenafil provides benefits in terms of exercise capacity when added to epoprostenol; however, these findings come from a trial that did not use the approved dosage of sildenafil. In conclusion, sildenafil is an effective oral treatment option for patients with PAH.     

Advances in treatment of pulmonary arterial hypertension: patent review

Introduction: Current therapeutic approaches for pulmonary arterial hypertension (PAH) commonly include use of prostacyclins, endothelin pathway antagonists or NO (nitric oxide) pathway modulators. These agents are non-specific and suffer from several important shortcomings including short half-lives, invasive routes of administration, higher dose and frequency requirements, and several dose-related systemic side effects. Hence, discovery of novel agents with improved therapeutic efficacy with respect to survival benefits and the development of non-invasive routes of administration are in critical need. Current research aimed at developing more selective therapies for PAH are focused both on agents acting on novel molecular targets, as well as, novel compounds acting on conventional pathways with improved characteristics.

Area covered: The present review covers recently filed (issued/application) patents (2010–2016) describing novel agents acting on investigational targets as well as novel compounds with improved characteristics acting on established targets. Patents describing combinations of conventional and investigational compounds are also discussed.

Expert opinion: PAH has recently been considered as cancer-like disease with over-proliferation of pulmonary arterial smooth muscle cells and endothelial cells. New cellular and molecular biological advances have revealed novel target/pathways involved in the pathogenesis and progression of PAH. Thus, discovery of agents that act on these novel pathways provides a promising avenue of research for improving therapeutic approaches for PAH.     

Bosentan for pulmonary arterial hypertension

Pulmonary arterial hypertension is an uncommon but disabling and often fatal condition, in which there is a sustained rise in pulmonary arterial pressure due to progressive obliteration of the pulmonary vascular bed. [symbol: see text] Bosentan (Tracleer-Actelion), which belongs to a new class of drugs called endothelin receptor antagonists, is now available for treating patients with pulmonary arterial hypertension. Here we assess whether bosentan offers worthwhile benefits in the management of patients with this condition.     

Prevalence of pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension in the United States

Abstract

Background:

The prevalence of pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) in the US is largely unknown. Prior research has estimated PAH prevalence in Europe at ～15–52 per million.     

Selexipag,a selective prostacyclin receptor agonist in pulmonary arterial hypertension: a pharmacology review

Introduction: Pulmonary hypertension is defined by a mean pulmonary artery pressure ≥25 mm Hg at rest. Management of pulmonary arterial hypertension (PAH) includes specific drug therapy with calcium channel blockers in vasoreactive patients, or drugs approved for PAH in non-reactive patients that target the endothelin, nitric-oxide and prostacyclin pathways.

Areas covered: The review covers receptor selectivity, pharmacokinetics, pharmacodynamics and adverse effects (AEs) of intravenous (IV) epoprostenol (synthetic prostacyclin); the prostacyclin analogs iloprost, beraprost, and treprostinil administered by IV, subcutaneous, inhaled or oral routes; and the oral selective prostacyclin receptor agonist selexipag.

Expert commentary: Development of a selective prostacyclin receptor agonist has aimed at identifying compounds with improved pharmacological properties. The high selectivity of selexipag, and its active metabolite ACT-333679, for the prostacyclin receptor, in conjunction with pharmacokinetic properties that reduce peak-trough fluctuations and the up-titration regimen used at the start of treatment, are collectively considered to minimize AEs associated with prostacyclin use. In a large phase 3 study, selexipag-associated AEs were consistent with those observed with drugs that target the prostacyclin pathway, and mainly mild to moderate in severity. The dosing flexibility afforded by oral selexipag may facilitate achieving the maximum therapeutic effect with acceptable tolerability in patients with PAH.     

贝前列素钠对慢性左心衰竭合并肺动脉高压患者的影响

目的 探讨贝前列素钠对慢性左心衰竭合并肺动脉高压患者的疗效和安全性.方法 选择慢性左心衰竭合并肺动脉高压患者50例,采用随机数字表法分成两组,分别给予常规治疗(常规组)和常规治疗基础上加贝前列素钠治疗(贝前列素钠,口服,每次40μg,每日3次),疗程12周.对所有患者进行基线评估,包括美国纽约心脏病学会(NYHA)分级、6 min步行距离(6MWT)、Borg呼吸困难评分、心肺血流动力学参数及脑钠肽(BNP)等,治疗随访12周后重复上述检查.结果 与常规组比较,贝前列素钠组治疗12周后NYHA功能分级、6MWT[(350±106)m比(320±101)m]、Borg呼吸困难评分[(3.0±2.4)分比(3.8±2.6)分]、肺动脉收缩压[(56±13)mmHg比(67±15)mmHg]、平均肺动脉压[(33±6)mmHg比(40±8)mm-Hg]和肺循环阻力[(3.5±1.5)WU比(4.6±1.6)WU]及肺毛细血管楔压均明显改善,差异有统计学意义(P<0.05).药物相关不良反应:贝前列素钠组用药初期1例患者有头痛伴面部潮红,1例患者出现恶心、呕吐,均可耐受,1周后症状消失.结论 贝前列素钠可改善慢性左心衰竭合并肺动脉高压患者的运动耐力、心肺血流动力学参数和临床症状且安全.     

Sitaxentan: in pulmonary arterial hypertension

Sitaxentan is a highly selective endothelin (ET)(A) receptor antagonist, with an approximately 6500 higher affinity for ET(A) than ET(B) receptors. In pulmonary arterial hypertension (PAH), elevated ET-1 levels are strongly correlated with disease severity and prognosis. Sitaxentan 100 mg once daily was efficacious in the management of moderate to severe PAH in the pivotal, 12-18 week, large (n > or = 98), well designed, placebo-controlled STRIDE-1, -2 and -4 trials. In the STRIDE-1 and -2 trials (the majority of patients had New York Heart Association [NYHA]/WHO functional class III PAH), sitaxentan-treated patients experienced significantly greater improvements from baseline in distance walked over 6 minutes (6MWD; primary endpoint in STRIDE-2) and in NYHA/WHO functional class than placebo recipients. In STRIDE-4, although there was no between-group difference in terms of improvements in 6MWD in the primary analysis of patients across all WHO functional classes (61% were functional class II) [primary endpoint], improvements in 6MWD significantly favoured sitaxentan versus placebo-treated patients in a post hoc subgroup analysis of those with WHO functional class III or IV disease. The beneficial effects of sitaxentan therapy on exercise capacity and NYHA/WHO functional class were maintained after up to 2 years' treatment. Treatment with sitaxentan for up to 2 years was generally well tolerated in clinical trials.