西地那非治疗肺动脉高压

肺动脉高压是一种相对少见但有潜在致命危险的疾病,多年来缺乏有效治疗药物。最近,美国FDA批准西地那非口服制剂Revatio可用于治疗肺动脉高压,为肺动脉高压患者的治疗带来了新的希望。本文就西地那非治疗肺动脉高压的机理,临床疗效及安全性等作一综述。     

N端脑钠肽原对西地那非联合辛伐他汀治疗女性肺动脉高压的评估

目的:探讨血浆N端脑钠肽原(NT-pro-BNP)对西地那非联合辛伐他汀治疗女性肺动脉高压患者疗效的评估情况。方法:将115例女性肺动脉高压患者分为西地那非联合辛伐他汀组(A组)38例(西地那非50mg,每日3次,辛伐他汀40mg,每日1次);西地那非组(B组)38例(西地那非50mg,每日3次);传统治疗组(C组)40例。连续治疗3个月,治疗前后测定右室收缩压、右室内径、肺功能[观察指标为第1秒用力呼气容积(FEV1)占用力肺活量(FVC)的百分比(FEV1/FVC)]、动脉血氧分压、6min步行距离(6-MWD)、明尼苏达心力衰竭生活质量(MLHFQ)评分及血浆NT-pro-BNP水平。结果:与C组比较,A、B组NT-Pro-BNP水平、右室收缩压及MLHFQ评分治疗后明显下降,FEV1/FVC及6-MWD较治疗前明显增加,且A组变化较B组更加显著;治疗后,A、B两组右室内径缩小、FEV1增加及动脉血氧分压提高,但A组并未显示出额外获益;血浆NT-Pro-BNP水平与右室收缩压呈正相关(r=0.72,P=0.003),与MLHFQ评分成正相关(r=0.47,P=0.007),与动脉血氧分压呈负相关(r=-0.57,P=0.013),与6-MWD亦呈负相关(r=-0.61,P=0.004)。结论:对西地那非联合辛伐他汀治疗多种病因所致的女性肺动脉高压,NT-pro-BNP可作为评估其疗效的一项简易、无创、可靠的生化指标。     

阿托伐他汀联合西地那非治疗肺动脉高压的临床研究

目的:评价阿托伐他汀、西地那非、阿托伐他汀和西地那非联合治疗肺动脉高压(PAH)的临床疗效.方法:选择45例PAH患者为研究对象.随机分为3组,每组15例,分别给予阿托伐他汀(阿托伐他汀组)、西地那非(西地那非组)、阿托伐他汀和西地那非联合(联合药物组)治疗,治疗前及治疗后6个月进行右心导管检查及6 min步行距离(6MWT)检测治疗效果.结果:3组治疗均能降低PAH患者肺血管阻力(P<0.05),西地那非组及联合药物组可以降低肺动脉压力(P<0.05),提高心脏指数(P<0.05 ),增加6MWT,其中联合2种药物较之单一用药更能降低肺动脉压力(P<0.05),增加6MWT(P<0.05),疗效进一步增强.结论:阿托伐他汀联合西地那非能有效治疗PAH患者,是一种相对经济有效的治疗方法.     

西地那非对肺动脉高压的作用

肺动脉高压是肺血管收缩、肺动脉内皮细胞和平滑肌细胞增殖以及原位血栓形成综合所致，由此引起肺血管阻力增加．肺动脉高压，最终导致右心衰竭而死亡的疾病。肺动脉高压不是一独立的疾病，而是一种病理生理状态，病因复杂。根据2003年9月召开的世界第三届肺动脉高压会议决定，仍基本维持Evian标准，肺动脉高压的诊断标准：肺动脉收缩压〉40mmHg（相当于多普勒超声检查三尖瓣血液反流速度〉310m／s），     

枸橼酸西地那非治疗原发性肺动脉高压二例

原发性肺动脉高压(PPH)是指原因不明的肺血管阻力增加引起持续性肺动脉压力升高,是一种进展性疾病,目前还没有根治方法.药物治疗的主要目标是降低肺动脉压力,改善症状及预后.利尿剂、强心剂一直用于治疗PPH并右心功能不全者.……     

辛伐他汀与肺动脉高压

肺动脉高压的基本病理改变有三个方面:肺血管收缩、肺血管重构和肺小血管内微血栓形成。现对辛伐他汀在肺动脉高压中的研究作一综述,并对可能机理进行了推测,认为辛伐他汀在肺动脉高压的治疗中可能有较好的应用前景。     

西地那非治疗肺动脉高压的研究进展

本文综述西地那非治疗肺动脉高压的临床应用进展.西地那非是一种选择性的磷酸二酯酶抑制剂,通过减少环鸟苷酸(cGMP)的降解发挥其治疗作用.研究表明西地那非和吸入一氧化氮一样可以用于急性血管舒张试验.西地那非单独应用或者和其它药物联合应用已经证明对于各种类型的肺动脉高压具有一定疗效,而且因其价格比前列环素类药物及内皮素受体拮抗剂便宜,因此其临床应用前景是引人注目的.然而在西地那非治疗肺动脉高压的临床应用方面目前尚缺乏多中心、大例数的研究资料.     

枸橼酸西地那非治疗原发性肺动脉高压1例

患者,女,36岁,因咳嗽、咯痰、易疲倦、气促伴双下肢水肿1个月入院。入院体检:BP108/80mmHg(1mmHg=0.133kPa),急性面容,高枕卧位,口唇发绀,颈静脉怒张,肝颈静脉回流征阳性,双肺底可闻及湿性啰音,叩诊心界向左扩大,心律齐,P2亢进,三尖瓣区可闻及3/6级收缩期吹风样杂音,肝脏在右肋     

西地那非治疗原发性肺动脉高压3例

例1:女性45岁,活动后气急1年,晕厥两次。心超测肺动脉收缩压97mmHg,右房右室增大。右心导管测肺动脉压为75/29mmHg,平均压47mmHg,血压95/62mmHg。诊断为原发性肺动脉高压(PPH),口服西地那非50mg,50min后测肺动脉压降至65/24mmHg,平均压降至38mmHg,但血压降至81/52mmHg,患者无明显症状。出院后口服西地那非25mg/bid,随访1周,症状有所改善,血压未见降低。 例2:女性47岁,头晕伴气急近10年。心超测肺动脉平均压85mmHg,多种药物治疗,效果不佳。行右心导管检查,提示在房间隔水平出现右向左分流,测肺动脉收缩压108mmHg,平均压65mmHg,口服西地那非50mg后,观察2h,肺动脉压均无明显变化。患者未出现不良反应。     

西地那非的新适应证:原发性肺动脉高压

原发性肺动脉高压治疗困难,过去所用药物因疗效不确切、给药途径复杂、价格昂贵等因素,无法推广.本文就西地那非(万艾可)治疗原发性肺动脉高压作一简介.     

西地那非在儿童先天性心脏病相关性肺动脉高压中的应用

目的:观察西地那非治疗先天性心脏病(CHD)相关性肺动脉高压(PAH)儿童患者的安全性和有效性。方法:选择13例年龄<18岁的CHD合并PAH的患者,口服西地那非每次0.25～1mg/kg,3次/d进行治疗。对比患者用药前后的6 min步行试验距离(6 MWT)、平均肺动脉压力(mPAP)、肺血管阻力指数(PVRI)、肺循环与体循环平均压比率(Pp/Ps)及肺循环与体循环阻力比率(Rp/Rs)的变化。结果:13例服药患者平均随访(9.5±6.2)个月,6 MWT平均增加(47.36±15.7)m,P<0.05。其中11例分别行用药前后的心导管检查,检查结果示mPAP从(87.1±8.4)mmHg(1 mmHg=0.133 kPa)降至(82.2±3.7)mmHg,P=0.1;PVRI从(24.5±7.4)Wood units m2降至(20.3±5.4)Wood units m2,P<0.05;Pp/Ps从(0.99±0.09)降至(0.89±0.05),P<0.05;Rp/Rs从(0.91±0.25)降至(0.86±0.17),P=0.5。所有患者服药期间无明显不良反应及肝肾功能异常。结论:西地那非在CHD相关性PAH儿童患者中应用是安全的,能显著改善患者的活动耐量,降低肺血管阻力。     

贝前列素钠联合西地那非治疗肺动脉高压的临床观察

目的:评价在西地那非基础上加用贝前列素钠治疗第一大类肺动脉高压患者的随机对照研究,探讨贝前列素钠及西地那非单药及联合治疗的疗效及安全性。方法:连续收集符合标准的肺动脉高压患者30例,随机分成两组,分别给予西地那非、西地那非加贝前列素钠治疗,疗程12周。对入组患者进行基线评估,包括右心漂浮导管,超声心动图,WHO肺动脉高压功能分级(WHO-FC)、6分钟步行距离(6MWT)等检查,治疗随访12周后重复上述检查,评价两组的疗效和安全性。结果:两组肺动脉高压患者经治疗12周后运动耐力均改善,6MWT提高,WHO-FC改善,超声心动图肺动脉收缩压、右心导管肺动脉平均压及全肺循环阻力均降低,贝前列素钠加西地那非组疗效明显优于单独西地那非组,差异有统计学意义。药物不良反应:联合治疗组有30%患者早期出现轻度头晕,面色潮红、头痛及腹泻等,2~3w后可以耐受。西地那非组有26%的患者出现头痛、脸红消化不良及鼻出血,经1周后均耐受,不良反应发生率差异无统计学意义。结论:贝前列素钠与西地那非联合用药组较单独用药组能更有效的降低肺动脉压力,改善临床症状且安全。     

肺动脉高压联合治疗方案效价研究

目的：探讨吸入型伊洛前列素和西地那非2种药物联合应用及单独用药在治疗重度肺动脉高压患者中的效价。方法：29例肺动脉高压患者随机分为单独应用伊洛前列素组（I组）、西地那非组（S组）和伊洛前列素续减合并西地那非递增的联合治疗组（I＋S组）,观察治疗4、12、24周时3组的临床疗效和经费。结果：治疗12周时,I组及I＋S组较S组在心排出量、6min步行距离和心功能WHO分级的改善方面均有明显差异（P〈0．05）;但I组与I＋S组相比疗效无显著差异：治疗24周时,3组疗效均无显著差异（P〉0．05）。12周及24周时I＋S组治疗费用较I组明显减少,分别节省32％及64％,S组治疗费用最低。结论：吸入伊洛前列素合并口服西地那非的续减递增联合治疗是重度肺动脉高压患者高效价的治疗方案。     

Addition of sildenafil in patients with pulmonary arterial hypertension with inadequate response to bosentan monotherapy

BACKGROUND:

Pulmonary arterial hypertension (PAH) remains a progressive disease despite improvement when using one of three medication classes: prostanoids, endothelin receptor antagonists or phosphodiesterase-5 inhibitors. Combination therapy has been proposed for patients with unsatisfactory response to monotherapy.

OBJECTIVES:

To examine the effect of adding sildenafil to bosentan on 6 min walk distance (6MWD) and New York Heart Association (NYHA) classification in patients with PAH who achieved inadequate improvement with bosentan monotherapy.

METHODS:

Patients with idiopathic PAH or connective tissue disease-associated PAH, and who had either self-reported inadequate improvement in exercise tolerance or a decline in 6MWD after initial improvement, were included in the study (n=10). Data on 6MWD and NYHA class at baseline (before initiation of bosentan), three and six months after baseline, second baseline (before initiation of combination therapy with sildenafil), and three and six months after second baseline were analyzed for any changes.

RESULTS:

Mean time from initiation of bosentan monotherapy to initiation of combination therapy was 558 days (range 150 to 900 days). Six months after initiation of bosentan, 6MWD increased by 57.2 m above the baseline of 314.4 m. Six months after combination therapy, 6MWD was 62.80 m higher than the baseline before initiation of combination therapy of 339 m (P<0.02). The overall increase in 6MWD six months after combination therapy was higher than the first baseline by 87.4 m (P not significant). NYHA functional class did not improve with combination therapy in all patients.

DISCUSSION:

Initiating combination therapy in patients who achieve an inadequate improvement in exercise tolerance with mono-therapy may result in further improvement in exercise tolerance.     

Acute and chronic effects of sildenafil in patients with pulmonary arterial hypertension

Sildenafil and inhaled nitric oxide (iNO) relax smooth muscle by inhibiting the degradation and stimulating the production of cyclic guanosine monophosphate, respectively. We compared the acute pulmonary vasodilator effects of sildenafil, iNO, and epoprostenol and asked whether the combination of iNO with sildenafil had additive pulmonary vasodilator effects. We assessed the effects of extended use of sildenafil in a small cohort of patients. Twenty patients with pulmonary arterial hypertension underwent an acute vasodilator trial with sildenafil (all patients), iNO and iNO plus sildenafil (11), and epoprostenol (19). We also provided sildenafil to patients who were ineligible for, or had clinical deterioration on epoprostenol, treprostinil, or bosentan. Mean+/-se pulmonary artery pressure dropped by 13+/-3%, 19+/-4%, 14+/-3%, and 26+/-4% with epoprostenol, iNO, sildenafil, and iNO+sildenafil, respectively. Cardiac index increased with epoprostenol and sildenafil. A correlation was found between the effects of iNO and epoprostenol. Nine out of ten patients who were started on long-term sildenafil treatment alone or in combination with other vasodilators had symptomatic improvement. Three died of right heart failure. In conclusion, sildenafil is a potent acute pulmonary vasodilator, an effect that is potentiated by combination with iNO. Long-term therapy of pulmonary hypertension with sildenafil alone or in combination with other agents appears to be safe and well tolerated.     

Successful treatment with sildenafil in systemic sclerosis patients with isolated pulmonary arterial hypertension: two case reports

We describe two systemic sclerosis (SSc) patients with isolated pulmonary arterial hypertension (PAH) who were given treatment with 50 mg oral sildenafil per day. We evaluated the efficacy of oral sildenafil for isolated PAH in SSc patients by direct assessment with cardiac catheterization before and 6 months after the initiation of sildenafil. Right-heart catheterization demonstrated decreased mean pulmonary artery pressure, decreased pulmonary vascular resistance, and increased cardiac output after treatment with sildenafil. Brain natriuretic peptide levels were gradually decreased. The 6-min walking distance was greatly extended. Moreover, the physical conditions of both patients were much improved. We recognized no adverse events. We propose that oral sildenafil may be beneficial as a selective pulmonary vasodilator and as long-term treatment in SSc patients with isolated PAH.     

西地那非治疗慢性阻塞性肺疾病相关肺动脉高压的研究进展

肺动脉高压(PH)是慢性阻塞性肺疾病(COPD)的重要并发症,也是COPD患者致死的主要原因之一,故及早控制肺动脉压力,可以改善患者的病程及预后.磷酸二酯酶-5抑制剂西地那非,能够有效地降低肺动脉压力和肺循环血管阻力,提高心输出量和心脏指数,改善心功能,从而用于特发性PH、血栓栓塞性PH、先天性心脏病等引起PH的治疗.但对COPD相关PH的治疗作用仍存在争议,需要大样本的研究资料加以证实.     

Impact of Sildenafil Therapy on Pulmonary Arterial Hypertension in Adults with Congenital Heart Disease

Background : It has been demonstrated that sildenafil is effective in patients with pulmonary arterial hypertension (PAH). However, the impact of sildenafil on PAH in adults with congenital heart disease (CHD) has been less investigated. Objective : In this prospective, open‐label, uncontrolled and multicenter study, 60 patients with PAH related to CHD received oral sildenafil (75 mg/day) for 12 weeks. The enrolled patients underwent six‐minute walk test (SMWT) and cardiac catheterization at the beginning and the end of the 12 weeks. The primary end point was the changes in exercise capacity assessed by SMWT; the secondary end point included assessment of functional class, evaluation of cardiopulmonary hemodynamics, and clinical worsening (defined as death, transplantation, and rehospitalization for PAH). Drug safety and tolerability were also examined. Results : Oral sidenafil significantly increased SMWT distances (422.94 ± 76.95 m vs. 371.99 ± 78.73 m, P < 0.0001). There was also remarkable improvement in Borg dyspnea score (2.1 ± 1.32 vs. 2.57 ± 1.42, P= 0.0307). Moreover, significant improvements in World Healthy Organization (WHO) functional class and cardiopulmonary hemodynamics were also discovered (mean pulmonary artery pressure, P= 0.0002; cardiac index, P < 0.0001; pulmonary vascular resistance, P < 0.0001). Side effects in this study were mild and consistent with reported studies. None of the enrolled patients experienced significant clinical worsening. Conclusions : This study confirmed and extended previous studies. It suggested that oral sildenafil was safe and effective for the treatment of adult patients with CHD‐related PAH.