PDE5抑制剂治疗ED研究进展

勃起功能障碍(ED)是中老年人的常见疾病。自1998年西地那非用于临床治疗ED以来,ED的治疗进入了一个新阶段。西地那非以其疗效确切、安全性高成为首选治疗。近年来新的PDE5抑制剂伐地那非和他达拉非相继问世,为口服药治疗ED提供了更多选择。本文就PDE5抑制剂的基础与临床研究成果作一综述,以期为临床医生选择使用提供参考。     

评估一项随机、双盲、安慰剂对照、平行研究——他达拉非OAD治疗对PDE5抑制剂初次治疗ED患者的疗效和安全性

<正>研究背景:已有的他达拉非OAD治疗研究的研究对象多为非PDE5抑制剂初次使用的患者。而PDE5抑制剂初次使用的患者对他达拉非OAD治疗的疗效和安全性相关数据,还很少。他达拉非OAD治疗的疗效和安全性在多个全球性临床研究中已被证实,他达拉非OAD连续治疗12和24周均耐受性良好并显著改善勃起功能。对罹患糖尿病的ED患者,他达拉非OAD治疗也显著改善勃起功能。两项开放标签的临     

服用他达拉非后第一个月的治疗反应可预示勃起功能障碍患者12个月内治疗的可持续性:来自DETECT临床试验的研究结果

DETECT临床试验是一项在欧洲进行的、前瞻性、多中心、观察性研究，所针对的受试者为在常规临床实践中，初次使用或改用他达拉非治疗勃起功能障碍（ED）的患者，为期12个月。该研究的目的是：在第12个月时，确定他达拉非的疗效以及患者坚持使用他达拉非治疗ED的相关因素。共有1900例年龄在18岁或以上的男性入选该研究，所有受试者均有ED病史，并将开始或改用他达拉非进行ED治疗。所选用的主要观察指标是：用“勃起功能国际指数一勃起功能域（IIEF—EF）评分”来评估受试者在基线时、第1月、第6月以及第12月的勃起功能，用多元变量回归分析来评估患者在12个月内坚持使用他达拉非进行治疗的相关因素。     

用新型非劣性研究设计比较他达拉非在各民族和各风险因素勃起功能障碍患者间的疗效和安全性研究

在美国进行的一项开放式多中心临床研究通过非劣性临床试验设计方式，以高加索白色人种作为参照组，对20mg他达拉非治疗美国黑色人种和拉美裔勃起功能障碍（ED）患者的疗效进行评估。该研究的次级目标是了解20mg他达拉非在不同ED患者人群中的疗效和安全性。共有1911例ED患者人选，并分人8个预先确定好的分组：（1～3组）高加索白色人种患者（参照组）、美国黑色人种或拉美裔患者、年龄≤65岁并且无糖尿病或抑郁症的患者；     

他达拉非对合并症患病率高的勃起功能障碍男性的疗效和安全性：MOMENTUS[美国全国他达拉非研究中勃起功能障碍男性的多项观测]的结果

有多种合并症（MCM）的勃起功能障碍（ED）患者，过去一直都比较难治，对于这些患者，疗效和安全性数据有限，这些有限的数据来自5型磷酸二酯酶抑制剂的开放性临床治疗试验。目的：一项多中心研究（美国全国他达拉非研究中勃起功能障碍男性的多项观测，MOMENTUS）评价了他达拉非在ED伴多种合并症的男性中的疗效和安全性。     

中长期使用他达拉非治疗勃起功能障碍患者的疗效及安全性研究

现有文献对5型磷酸二酯酶抑制剂治疗多种类型勃起功能障碍（ED）的疗效进行了大量报道。但是，现有的资料缺乏这些治疗方法的中长期疗效和安全性内容。为了评估中长期使用他达拉非治疗脊髓损伤（SCI）性ED患者的疗效和安全性，最近有研究者进行了一项两阶段性临床试验。第1阶段：在2003年3月到2007年3月之间，选入103例SCT性ED患者，其平均年龄为39岁。     

他达拉非治疗勃起功能障碍:良好的安全性和耐受性

他达拉非是新型的5型磷酸二酯酶(PDE5)抑制剂,口服用于治疗勃起功能障碍(ED)。在具有卓越的36h疗效的同时,他达拉非治疗ED的安全性和耐受性均十分良好,不良事件多为一过性的轻、中度事件。ED患者往往伴发多种基础疾病或同时需服用多种药物,因此,详细地了解他达拉非在一般人群以及某些特殊的高危人群中的安全性是十分重要的,本文就这方面内容进行了综述。     

他达拉非治疗ED以及用药选择的偏爱研究

自从5型磷酸二酯酶抑制剂(PDE5-I)出现后,ED的治疗发生了革命性的变化。目前市场上共有3种PDE5-I,相似的疗效、安全性和耐受性使ED患者和医生有了更多的选择余地。他达拉非以其半衰期长的特点拥有较宽的治疗窗,并且不受饮食和酒精影响,能允许ED患者自由、自然而不必刻意地计划性生活,从而恢复自信与自尊,改善与性伴侣的关系,提高生活质量。懂得患者的偏爱对药物选择具有十分重要的指导意义,尽管目前尚无完美的偏爱研究设计,但众多研究均显示他达拉非更得到患者偏爱。     

评估口服他达拉非治疗加拿大勃起功能障碍患者疗效和安全性的随机、双盲、平行、安慰剂对照临床研究

目前勃起功能障碍（ED）的发病率很高，并且往往得不到很好的治疗。最近在加拿大进行了一项为期12周的双盲、平行、安慰剂对照研究，共有25家研究单位参予，对口服磷酸二酯酶5抑制剂——他达拉非治疗ED的疗效和安全性进行了评估。在该研究中，器质性、心理性以及混合性ED患者按照基线ED轻重程度进行分层，     

一项随机、开放标签的交叉对比研究:他达拉非每日一次与他达拉非或西地那非临时服用对ED患者性自信及其他疗效的对比

<正>PDE5抑制剂的疗效维持时间对ED患者改善性交时间顾虑、增强性自信和性主动、改善与性伴侣亲密度具有重要意义。他达拉非OAD治疗比短效PDE5抑制剂如西地那非临时服用更有效改善ED患者的性心理。评价对于PDE5抑制剂疗效满意的ED患者,他达拉非OAD治疗是否比西地那非PRN治疗更好地改善     

Efficacy and safety of on-demand tadalafil for the treatment of erectile dysfunction in South-East Asian men

AIM: Tadalafil is an inhibitor of phosphodiesterase type 5 used for the treatment of erectile dysfunction (ED). The efficacy and safety of tadalafil have been evaluated extensively in Western populations. Our aim was to assess the efficacy and safety of on-demand tadalafil for the treatment of ED in South-East Asian men. METHODS: This was a randomized, double-blind, placebo-controlled study of men with mild to severe ED of various etiologies randomized to receive placebo (n = 122), tadalafil 10 mg (n = 120), or tadalafil 20 mg (n = 125), taken as needed (maximum once daily) for 12 weeks. Efficacy assessments included the International Index of Erectile Function (IIEF), the Sexual Encounter Profile (SEP) diary, and a Global Assessment Question (GAQ). RESULTS: Men from China, Singapore, and the Philippines participated in this trial (n = 367). Compared with placebo, tadalafil significantly improved erectile dysfunction on all efficacy outcomes (P < 0.001). Patients receiving tadalafil 10 mg and 20 mg experienced a significant mean improvement of 8.1 and 8.7, respectively, in the IIEF Erectile Function (IIEF-EF) domain score from baseline (vs placebo 2.4, P < 0.001). In patients receiving tadalafil 10 mg and 20 mg, the mean per-patient success rate for intercourse attempts (SEP3) was 62% and 70%, respectively, compared with 32% for the placebo group (P < 0.001). Of patients who received tadalafil 10 mg and 20 mg, 81% and 86% reported improved erections at endpoint (GAQ) compared with 44% in the placebo group (P < 0.001). The most common adverse events reported by patients were headache, back pain, dyspepsia, and dizziness. CONCLUSIONS: Tadalafil was an effective and well-tolerated treatment for South-East Asian men with ED.     

Phosphodiesterase type 5 inhibitors for the treatment of erectile dysfunction in patients with diabetes mellitus

Sildenafil, a phosphodiesterase 5 (PDE5) inhibitor, has become a first-line therapy for diabetic patients with erectile dysfunction (ED). The efficacy in this subgroup, based on the Global Efficacy Question, is 56% vs 84% in a selected group of non-diabetic men with ED. Two novel PDE5 inhibitors, tadalafil (Lilly ICOS) and vardenafil (Bayer), have recently completed efficacy and safety clinical trials in 'general' and diabetic study populations and are now candidates for US FDA approval. A summary analysis of the phase three clinical trials of sildenafil, tadalafil and vardenafil in both study populations is presented to provide a foundation on which the evaluation of the role of the individual PDE5 inhibitors for the treatment of patients with ED and DM can be built.     

他达拉非治疗ED疗效和安全性新进展

他达拉非——长效5型磷酸二酯酶(PDE5)抑制剂是治疗勃起功能障碍(ED)的首选药物之一。许多临床研究证实其在普通ED患者、老年患者以及伴有糖尿病、脊髓损伤或前列腺癌术后患者中有较好的疗效和良好的安全性及耐受性,而且其独特的长达36 h的时间窗不仅增强了患者的自信心,更改善了患者及其伴侣的生活质量。     

Efficacy and safety of long‐term tadalafil 5 mg once daily combined with sildenafil 50 mg as needed at the early stage of treatment for patients with erectile dysfunction

This study aimed to evaluate the efficacy and safety of long‐term and low‐dose tadalafil combined with sildenafil as needed at the early stage of treatment for erectile dysfunction (ED). We enrolled 180 patients with ED 1 : 1 to tadalafil 5 mg once daily or once‐a‐day tadalafil 5 mg combined with sildenafil 50 mg as needed. The efficacy measures included the 5‐item version of the International Index of Erectile Function (IIEF‐5) and the Sexual Encounter Profile (SEP). The safety was assessed by observing drug tolerability and adverse events. Total IIEF‐5 scores of patients with severe ED in combined medication group were significantly higher than in tadalafil alone group. Question 2 scores of IIEF‐5 of patients with moderate and severe ED in combined medication group were significantly higher than in tadalafil alone group. The significant improvement in question 3 scores of IIEF‐5 existed only in patients with severe ED receiving combined medication. The percentage of ‘yes’ responses to SEP4, SEP5 and partner's SEP3 were improved significantly in combined medication group. There was no difference between two groups in the incidence of adverse events. Our results suggest that combined medication can better improve erectile function, especially for patients with severe ED.     

Efficacy of tadalafil in the treatment of erectile dysfunction in hypertensive men on concomitant thiazide diuretic therapy

Many men with erectile dysfunction (ED) have hypertension as a comorbid condition. Recent guidelines recommend thiazide diuretics as first-line therapy for hypertension. We analyzed data from 14 randomized, double-blind, placebo-controlled trials (N=2501) to evaluate the efficacy of tadalafil 20 mg for the treatment of ED in men on thiazides. Of the 2501 patients, 163 were on concomitant thiazides (116 tadalafil/47 placebo) and 159 (98%) were reported to have hypertension. The primary efficacy measures were mean change from baseline in the international index of erectile function (IIEF) erectile function (EF) domain and the proportion of 'yes' responses to sexual encounter profile (SEP) Questions 2 and 3. The tadalafil group showed a significantly (P<0.001) greater mean baseline to endpoint improvement on all efficacy outcome measures compared to placebo-treated patients regardless of concomitant thiazide use. More importantly, the responses to tadalafil were similar regardless of concomitant thiazide use. Additionally, responses to tadalafil were comparable between thiazide and nonthiazide users regardless of baseline ED severity (P>0.05).     

同期内使用3种PDE5抑制剂治疗ED的经验

目的:观察与比较同期内使用3种PDE5抑制剂治疗ED患者的疗效,满意情况和不良反应。分析影响患者疗效、接受度、倾向性的因素。方法:11个月在门诊应用3种PDE5抑制剂治疗ED患者331例。使用西地那非134例,他达拉非88例,及伐地那非109例。医师详细指导药物的应用,注意事项,观察的内容等,并互留电话,列表登记、随访。结果:复诊或电话随访时间,结果为:①获得良好的疗效及满意率为西地那非72例(79.12%),他达拉非52例(78.78%),伐地那非63例(81.81%)。②PDE5抑制剂单纯或交叉应用的资料分析显示:青年患者或新婚者,偏好伐地那非;③中青年患者倾向于他达拉非;中老年及较长期应用PDE5抑制剂的患者多选用西地那非。3种PDE5抑制剂用于早泄均有一定疗效。④对不能继续用此类药治疗ED的原因进行了分析,分别为:价高,不治本,效果差,耽心不良反应。结论:①同期3种PDE5抑制剂治疗ED的疗效基本相近。亦各有一些优势和特点。②3种PDE5抑制剂的安全性均好,一般、轻度不良反应相近,中度、特殊的不良反应少,严重不良反应均无发生。③PDE5抑制剂的疗效观察,目前众多的问卷、量表实际均仍以主观的感受为主。对同一个人以相同形式、相同问题、繁简一致阐述,获得的有关疗效满意情况、感受等简易回答是有可比性、可信度和实用性的。     

Prevalence and medical management of erectile dysfunction in Asia

Erectile dysfunction (ED) is an important worldwide health issue that has a significant negative impact on the quality of life and life satisfaction of both the affected individual and his partner. Here we review the prevalence of ED in Asia, associated factors that may influence sexual attitudes and sexual behaviours, and randomized clinical trials (RCTs) of phosphodiesterase-5 (PDE-5) inhibitors to evaluate the clinical efficacy and safety of PDE-5 inhibitors in Asian men. We searched for English-language articles in MEDLINE and PubMed from January 2000 to September 2010. Our results showed that the overall reported prevalence rate of ED in Asia ranged widely, from 2% to 88%. This finding indicates that ED is a common and major health problem in this region. However, sociocultural and economic factors in Asia prevent people from seeking and obtaining appropriate medical care. We found reports on five kinds of PDE-5 inhibitors for the management of ED: sildenafil, vardenafil, tadalafil, udenafil and mirodenafil. The results of RCTs showed that these five PDE-5 inhibitors are more effective than placebo in improving erectile function in Asian men with ED and that these drugs have similar efficacy and safety profiles.     

Efficacy and satisfaction rates of oral PDE5is in the treatment of erectile dysfunction secondary to spinal cord injury: a review of literature

Concept

Decreased sexual function is a major concern of men with spinal cord injuries (SCIs). Treatment of erectile dysfunction (ED) through oral pharmacotherapies has been proven to be an effective way to address and treat this concern.

Objective

To find an efficacious and satisfactory treatment ED secondary to SCI through the compilation of studies that utilized the International Index of Erectile Function (IIEF) when testing phosphodiesterase V inhibitors (PDE5i).

Method

Ten articles, which used the IIEF to study satisfaction and/or efficacy of PDE5is sildenafil, tadalafil, and vardenafil in the treatment of ED were reviewed and analyzed. Through the use of a self-made grading scale the value of each article was determined for this research.

Results

Sildenafil, tadalafil, and vardenafil all have been proven to be effective in treating ED in men with SCI. While sildenafil is the most thoroughly studied ED treatment for patients with SCI, tadalafil has a longer time duration effectiveness, which allows for more spontaneity in the sexual experience. Minimal adverse effects have been noted in patients with SCI using these medications; headache, flushing, and mild hypotension are the most common. In articles that study satisfaction, patients show great improvement over baseline with the use of these medications.

Conclusion

Although there is a need for further research on the safety in long-term use of tadalafil and vardenafil, comparative studies done on all three medications show no statistically significant difference in effectiveness or satisfaction. New medications and treatment options, such as avanafil, are being studied in hope of continued improvement of sexual function in men with SCI.