A 6-month,prospective, observational study of PDE5 inhibitor treatment persistence and adherence in Middle Eastern and North African men with erectile dysfunction

Abstract

Background:

Erectile dysfunction (ED) negatively impacts quality of life. Phosphodiesterase type 5 inhibitors (PDE5Is) are effective in treating ED; however, rates of discontinuation remain high.     

小剂量PDE5i联合西地那非治疗糖尿病性男性勃起功能障碍的效果分析

目的 探讨小剂量PDE5i联合西地那非治疗糖尿病性男性勃起功能障碍的效果.方法 选取本院收治的110例ED患者,将其随机分为观察组和对照组,每组55例,其中对照组单独服用5型磷酸二酯酶抑制剂(PDE5i),观察组在此基础上加用西地那非,均治疗3月后比较两组患者ⅡEF-5评分改变情况、治疗效果以及不良反应情况.结果 治疗后两组轻、中、重度患者的ⅡEF-5量表评分均较治疗前明显改善,P＜0.05,且观察组重度患者的ⅡEF-5量表评分以及Q2问题得分明显高于对照组,组间比较差异有统计学意义,P＜ 0.05.经过12周的治疗后对照组总有效率为76.36％,观察组为92.73％,治疗总有效率组间比较差异有统计学意义,x2=6.142,P＜0.05.对照组不良反应的发生率为27.27％,观察组为29.09％,组间比较差异无统计学意义,P＞0.05.结论 小剂量PDE5i联合西地那非应用于糖尿病ED患者的治疗能够较快达到满意的勃起硬度,同时通过对血管内皮功能的修复起到良好的治疗效果,值得推广应用.     

Efficacy of vardenafil for the treatment of erectile dysfunction in men with hypertension:a meta-analysis of clinical trial data

ABSTRACT

Objective: To review the evidence evaluating the efficacy of vardenafil in subgroups of hypertensive patients with erectile dysfunction (ED).

Methods: Meta-analysis of randomized, double-blinded, placebo-controlled, flexible-dose vardenafil clinical trials that were ≥12 weeks in duration evaluated men with a ≥ 6-month history of ED and required a ≥?50% failure rate in baseline sexual attempts. The primary endpoints analyzed were the erectile function domain of the International Index of Erectile Function questionnaire (IIEF‐EF) and Sexual Encounter Profile questions 2 (SEP2) and 3 (SEP3).

Results: Eight clinical trials were included (n = 2427 patients) consisting of 839 patients (35%) with a self-reported diagnosis of hypertension (HTN): 498 in the vardenafil and 341 in the placebo groups. Vardenafil's efficacy was evidenced by an average increase of 8.9 points in the IIEF‐EF (95% CI: 7.4, 10.5) at week 12 compared to placebo, with individual trial values ranging from 16.4 to 26.1 and 11.3 to 17.8 for the vardenafil and placebo groups, respectively. Vardenafil also increased success rates for the ability to obtain erections (SEP2) by 32.4% (95% CI: 27.4%, 37.5%) over a 12-week timeframe compared to placebo, with individual trial values ranging from 57.2% to 92.2% for vardenafil and 32.0% to 66.9% for placebo. Similarly, success rates for the ability to maintain erections (SEP3) improved 38.0% (95% CI: 29.5%, 46.6%) compared to placebo, with individual trial values ranging from 41.7% to 88.2% for vardenafil and 20.5% to 51.4% for placebo. Vardenafil was equally efficacious in improving IIEF‐EF, SEP2, and SEP3 in those with and without self-reported HTN.

Conclusion: This meta-analysis demonstrated that vardenafil was significantlly more efficacious than placebo for the treatment of ED in patients with comorbid HTN and offered similar treatment benefits in patients without HTN.     

Correlation of improved erectile function and rate of successful intercourse with improved emotional well-being assessed with the Self-Esteem And Relationship questionnaire in men treated with sildenafil for erectile dysfunction and stratified by age

ABSTRACT

Background: The quality of life consequences of erectile dysfunction (ED) include depression, anxiety, and loss of self-esteem. The Self-Esteem And Relationship (SEAR) questionnaire is a validated, patient-administered, psychometric instrument specific to ED.

Objective: To determine correlations between erectile function (EF), intercourse success, and emotional well-being measured with the SEAR questionnaire in men treated with sildenafil citrate for ED and stratified by age (< 50 years, 50–65 years, and > 65 years).

Research design and methods: This was an open-label, flexible-dose trial of sildenafil (25, 50 and 100?mg) administered for 10 weeks to 382 men with ED (mean ± SD age, 55 ± 13 years; mean ED duration, 4 years), which was conducted at 62 centers in the United States.

Main outcome measures: Analysis (by intent-to-treat, n = 368) of the change from baseline to the week‐10 endpoint in the SEAR questionnaire Self-Esteem subscale, the intercourse success rate (percent of occasions at which an erection that lasted long enough for successful intercourse was achieved), and their correlation.

Results: For the overall population, there was mean ± SD improvement (?p < 0.0001, paired t‐tests) in the Self-Esteem subscale (56 ± 25 to 79 ± 22) and intercourse success rate (21 ± 30% to 70 ± 36%), which showed positive correlation (?p < 0.0001). Secondary outcomes (i.e., EF domain of the International Index of Erectile Function; event log frequency of erection hard enough for sexual intercourse and of ejaculation/orgasm) also improved (?p < 0.0001) and correlated positively with the SEAR Self-Esteem subscale and Sexual Relationship domain (?p < 0.05 for all correlations). All 10 correlations were positive (?p < 0.05) in men aged 50 to 65 years, eight were positive in men aged > 65 years, and six were positive in men aged < 50 years. The most common treatment-related adverse events were mild-to-moderate headache (12% of patients), vasodilatation (7%), and rhinitis (4%).

Conclusions: Men treated with sildenafil for ED demonstrated improved erectile function and an increased intercourse success rate, which correlated positively with improvement in SEAR measures of self-esteem and sexual relationship.     

The efficacy of tadalafil in improving sexual satisfaction and overall satisfaction in men with mild,moderate, and severe erectile dysfunction: a retrospective pooled analysis of data from randomized,placebo-controlled clinical trials

ABSTRACT

Background: Satisfaction with the sexual experience is considered important when evaluating the impact of treatments for erectile dysfunction (ED), yet satisfaction has been infrequently assessed in clinical trials.

Objective: To evaluate satisfaction with, and enjoyment of, the sexual experience in men with ED enrolled in 11 placebo-controlled clinical trials of tadalafil.

Study design and methods: Retrospective pooled analysis of data from 11 randomized, double blind, placebo-controlled clinical trials of tadalafil. Men with mild (N = 838), moderate (N = 558), or severe (N = 703) ED who were randomized to tadalafil 10?mg or 20?mg or placebo taken as needed for 12 weeks were included in this analysis. Efficacy measures included the International Index of Erectile Function (IIEF). Reported herein are the scores on the IIEF overall satisfaction domain and individual IIEF questions (IIEF‐Q7, satisfaction with intercourse; and IIEF‐Q8, enjoyment of intercourse).

Results: At least moderate satisfaction (IIEF overall satisfaction domain) was reported by 55% and 72% of patients with mild ED taking tadalafil 10?mg and 20?mg, respectively, compared with 33% taking placebo (?p < 0.002); 60% and 65% vs. 19% of patients with moderate ED (?p < 0.001); and 32% and 49% vs. 9% with severe ED (?p < 0.001). Satisfactory intercourse during most attempts or almost always/always (IIEF‐Q7) was reported by 59% and 79% of patients with mild ED taking tadalafil 10?mg and 20?mg vs. 32% taking placebo (?p < 0.001); 52% and 65% vs. 18% with moderate ED (?p < 0.001); and 28% and 49% vs. 5% with severe ED (?p < 0.001). Highly or very highly enjoyable intercourse (IIEF‐Q8) was reported by 45% and 63% of patients with mild ED taking tadalafil 10?mg and 20?mg vs. 21% taking placebo (?p < 0.001); 43% and 56% vs. 16% with moderate ED (?p < 0.001); and 19% and 44% vs. 5% with severe ED (?p < 0.001).

Conclusions: Compared with placebo, tadalafil 10?mg and 20?mg improved overall satisfaction with the sexual experience, intercourse satisfaction, and intercourse enjoyment in men with mild, moderate, and severe ED.     

Oral anticoagulant adherence and switching in patients with atrial fibrillation: A prospective observational study

BackgroundAdherence to oral anticoagulants (OACs) in patients with atrial fibrillation (AF) is important in preventing stroke. The dominance of retrospective studies using administrative data has led to a lack of data on psychosocial determinants of adherence and prevented comparison of adherence between OAC drug classes. OAC switching is another aspect of adherence that is unexplored.MethodsA prospective design was utilized to measure AF patients’ self-reported adherence and OAC switching, and to identify their clinical, demographic, and psychosocial determinants. Participants were recruited from specialized AF clinics in Canada and followed for up to 2 years. Data were collected via telephone every 3–4 months using a structured survey. Adherence was measured using the Morisky Medication Adherence scale (©MMAS-8).ResultsThe included participants (N = 306) were followed for a median follow up time of 14.1 months and had an average of 3.2(SD 1.4) study visits. The mean self-reported adherence on the ©MMAS-8 was 7.28(SD 0.71) for patients receiving care at specialized AF clinics. Older age, experiencing a bleed, and higher satisfaction with the burden of medications were significantly associated with higher adherence. Drug class did not have any significant impact on adherence. 7.8% of the cohort experienced a switch with most of them being from warfarin to DOAC. Taking warfarin as the index medication, experiencing a bleed and older age were significantly associated with higher odds of switching.ConclusionPatients with AF reported high adherence to their OAC therapy however being on DOAC may not translate to better adherence compared to VKA. Improving satisfaction with the burden of therapy is important in improving adherence.     

Phosphodiesterase type 5 inhibitor therapy: identifying and exploring what attributes matter more to clinicians and patients in the management of erectile dysfunction

ABSTRACT

Background: Erectile dysfunction (ED) is increasingly being recognized as a sentinel marker of future subsequent cardiovascular disease (CVD). Predicted increases in the prevalence of ED are due to a combination of an aging population and the increasing presence of comorbid conditions (hypertension, dyslipidemia, and diabetes). The dichotomy of the situation is that ED is often associated with these comorbidities, potentially leading to greater CVD risk, and conversely, these comorbidities have also been shown to increase the risk of developing ED. The successful treatment of ED with phosphodiesterase type 5 (PDE5) inhibitor therapy, therefore, is of paramount importance because it not only plays a critical role in restoring erectile function, but also provides clinicians with the opportunity to mitigate existing cardiovascular comorbidities or prevent the occurrence of CVD in this patient population.

Methods: This review is based on an electronic literature search of databases, including MEDLINE/PubMed, with information selected for its relevance to PDE5 inhibitor therapy comprising efficacy (e.g., first-dose success) in men with ED with or without comorbidities, onset and duration of action at specific time points, and patient preference.

Results: The introduction of PDE5 inhibitors represented a major advance in the treatment of ED. In spite of the availability of these agents, a large percentage of men are still not being treated, in many cases because of their reluctance to seek medical help. Moreover, many men who start treatment with PDE5 inhibitors discontinue treatment. Reasons for discontinuation are many and complex, including lack of initial or first-time success. Although of major concern to both patients and clinicians, there remains limited published clinical data on this specific parameter in the pertinent patient population and from prospective, randomized clinical studies.

Conclusion: Data from studies suggests that the available PDE5 inhibitor therapies are effective in treating men with ED, including those who have increased CVD risk and those who have clinically identified cardiovascular comorbidities such as hypertension, dyslipidemia, and/or diabetes. According to data from studies, the attributes of PDE5 inhibitor therapy that matter more to clinicians and patients and that hold influence over treatment compliance include effectiveness in patients with cardiovascular comorbidities, first dose effectiveness or early success, rapid onset of action, reliability, and tolerability.     

中医药行气活血配合西地那非治疗勃起功能障碍

目的 提出男子“以血为用”的新观点,观察运用中医行气活血方药配合口服西地那非（万艾可）治疗勃起功能障碍（ED）的疗效。方法 将146例ED患者随机分为两组,治疗组86例,内服行气活血中药,房事前1h 口服万艾可50mg;对照组60例仅房事前1h口服万艾可50mg。两组均以30d为1个疗程。结果 治疗组显效78例,无效8例,有效率90．7％;对照组显效49例,无效11例,有效率81．7％。两组有效率比较,差异有显著意义（P〈0．05）。结论 中医药行气活血配合万艾可能显著提高ED治疗的有效率。     

Sildenafil citrate for erectile dysfunction in men with diabetes and cardiovascular risk factors: a retrospective analysis of pooled data from placebo-controlled trials*

ABSTRACT

Objective: Cardiovascular (CV) risk factors are associated with an increased risk of erectile dysfunction (ED). In men with diabetes mellitus (DM), pooled from clinical trials of sildenafil treatment for ED, this retrospective analysis determined efficacy and safety, overall and in subgroups with additional CV risk (i.e., hypertension, dyslipidemia, and smoking).

Research design and methods: From the manufacturer's database of worldwide research, 12‐week data from men with DM were pooled from randomized, double-blind, placebo-controlled trials of flexible-dose sildenafil (25, 50, or 100?mg, PRN) for ED.

Main outcome measures: Question 3 (achieving an erection), question 4 (maintaining an erection), and the Erectile Function domain of the International Index of Erectile Function; percentage of successful intercourse attempts according to patient event logs; and response to a global efficacy question (GEQ). Differences between groups were determined using logistic regression (percentage of responders according to GEQ) and analysis of covariance (all other outcomes).

Results: Inclusion criteria were met by 11 trials and by 974 men with DM and ED who were randomized to placebo (n = 482) and sildenafil (n = 492) within the selected trials. For all outcomes, overall and regardless of additional CV risk, the benefit was greater for sildenafil versus placebo (?p ≤ 0.0001), including 3-fold more men responding that sildenafil treatment improved their erections (62% vs. 18%) and a more than doubling of the mean ± standard error percentage of successful sexual intercourse attempts (52.6 ± 5.0 vs. 22.4 ± 5.1). Adverse events were mild to moderate and included (sildenafil vs. placebo) headache (5% vs. 2%), flushing (7% vs. 2%), and dyspepsia (4% vs. 0%), which is consistent with the profile in the general population of men treated with sildenafil for ED.

Conclusion: This retrospective analysis of pooled data showed that sildenafil was well tolerated and improved erectile function and intercourse success in men with ED and DM, regardless of additional CV risk factors.     

Factors associated with medication adherence and persistence of treatment for hypertension in a Medicaid population

BackgroundNon-adherence with antihypertensive therapy is a significant problem. Prior research has generally focused upon one drug or one drug class. Current information across multiple antihypertensive drug classes is limited.ObjectivesTo describe the initial treatment of recipients of Louisiana Medicaid with newly-diagnosed hypertension; evaluate differences in adherence and persistence rates among multiple antihypertensive drug classes; and test the association of drug classes, race, gender, age and comorbidity with adherence and persistence to drug therapy.MethodsIn a retrospective analysis of administrative claims data, initial therapy was described by type and drug class for 4544 Medicaid recipients with newly-diagnosed hypertension. Recipients were placed into cohorts based upon drug classes (diuretics, beta-blockers, angiotensin-II receptor blockers, angiotensin converting enzyme inhibitors, and calcium channel blockers). Persistence with drug therapy and Medication Possession Ratios (MPR) were calculated for 6-month and 12-month periods following diagnosis. Drug class and demographic variables were used as predictor variables in logistic regression analyses of persistence and MPR.ResultsRecipients in the study group were primarily female (66%) and Black (65%). Recipients initially were treated with monotherapy (33%), multiple drugs (11%), fixed combinations (8%) or no drugs (48%). After one year, 62% of recipients were not receiving drug therapy. Persistence rates by cohort ranged from 26% to 42% at 6-months following diagnosis, and 14%–28% at 12-months. The proportion of recipients by cohort with MPRs of 0.8 or above ranged from 43% to 60% at 6-months and 25%–42% at 12-months. Race, comorbidities, and initial drug therapy were significant predictors of both persistence and MPR.ConclusionsWithin this study group, adherence and persistence to medication therapy were less than optimal. Future efforts to improve compliance with medication therapy could be focused upon specific groups having poor adherence and/or persistence within the drug class cohorts analyzed in this study.     

A Rho-kinase inhibitor,soluble guanylate cyclase activator and nitric oxide-releasing PDE5 inhibitor: novel approaches to erectile dysfunction

Approximately 50% of men aged over 40 suffer from male erectile dysfunction. Treatment options have widened since the launch of the phosphodiesterase type 5 (PDE5) inhibitor, sildenafil citrate (Viagra?). However, a certain portion of the patient population, such as diabetics, do not gain significant benefit from PDE5 inhibitors, possibly due to a lack of endogenous nitric oxide. Therefore, new treatment modalities based on the absence of endogenous nitric oxide have been developed. Among them are Rho-kinase inhibitors, soluble guanylate cyclase activators and nitric oxide-releasing PDE5 inhibitors. The available data concerning these compounds will be summarised and their therapeutic potential for male erectile dysfunction will be discussed.     

Preliminary observations on the use of propionyl-L-carnitine in combination with sildenafil in patients with erectile dysfunction and diabetes

ABSTRACT

Background: Histamine receptor activation and degranulation of mast cells are the mechanisms by which the ocular itching, hyperemia, chemosis, eyelid swelling, and tearing of seasonal allergic conjunctivitis are induced. Some of the topical solutions available as anti-allergy therapies are intended to interfere with these mechanisms, and the body of research regarding the capabilities of these therapeutic molecules continues to expand.

Objective: To review the currently available literature regarding one topical ophthalmic anti-allergy agent, olopatadine (Patanol), and its anti-histaminic and mast cell stabilizing actions, both in pre-clinical and clinical settings.

Design and methods: Relevant research of laboratory, animal model, and clinical trial studies performed using olopatadine was reviewed. MEDLINE literature searches were conducted and supplemented by additional reports which furthered relevant discussion or were necessary to verify the information resulting from original searches.

Results: Olopatadine demonstrates unique properties both pre-clinically and clinically which differentiate it from other therapeutic molecules in its class of dual action mast cell stabilizer/anti-histamine. Its non-perturbation of cell membranes, human conjunctival mast cell stabilization in vivo and in vitro, and superior efficacy as compared to other topical anti-allergic medications including mast cell stabilizers, anti-histamines, and dual action agents, all contribute to olopatadine's profile.

Conclusions: Peer-reviewed literature suggests that olopatadine is clinically superior to the other anti-allergic molecules because of its strong anti-histaminic qualities and its unique ocular mast cell stabilizing properties.     

金蚧片联合伐地那非治疗勃起功能障碍的疗效观察

目的探讨金蚧片联合伐地那非治疗勃起功能障碍的临床疗效。方法选取2018年11月—2020年11月在天津市泰达医院泌尿外科门诊治疗的96例勃起功能障碍患者,根据随机数字表法分为对照组和治疗组,每组各48例。对照组口服盐酸伐地那非片,10 mg/次,在性交前25～60 min服用。治疗组在对照组的基础上口服金蚧片,4片/次,3次/d。两组连续服用药物8周。观察两组的临床疗效,比较两组治疗前后阴茎血流动力学指标、国际勃起功能评分-5(IIEF-5)、勃起硬度评分(EHS)、睾酮水平变化情况。结果治疗后,治疗组总有效率是97.92%,显著高于对照组的81.25%(P0.05)。治疗后,治疗组患者阴茎血流动力学中舒张末期峰值流速(EDV)、血流阻力指数(RI)均高于对照组,但收缩期峰值流速(PSV)低于对照组(P0.05);且治疗后,治疗组患者阴茎血流动力学中各指标改善优于对照组(P0.05)。治疗后,两组患者IIEF-5、EHS评分均显著升高;治疗后,治疗组IIEF-5、EHS评分均显著高于对照组(P0.05)。治疗后,两组患者睾酮水平显著升高(P0.05),且治疗后治疗组睾酮水平高于对照组(P0.05)。结论金蚧片联合伐地那非治疗勃起功能障碍疗效显著,可有效改善阴茎勃起功能,且具有较高的治疗安全性,值得临床借鉴与推广。     

小剂量持续服用他达拉非对糖尿病性勃起功能障碍的疗效观察

目的探讨和观察糖尿病性勃起功能障碍患者采用小剂量持续服用5型磷酸二脂酶抑制剂(PDE5i)治疗的临床效果与副反应。方法 51例糖尿病性勃起功能障碍(ED)患者口服PDE5i(他达拉非)5 mg每日1次,共12周。疗效指标包括"国际勃起功能指数"(IIEF-5)、性活动日志(SEP)、全球评估问卷(GAQ)。结果 51例患者勃起功能改善者42例,有效率为82.3%;治疗后IIEF-5评分有显著性提高(P<0.05);治疗后阴茎插入的成功率和保持勃起至完成性交的成功率明显增高(P<0.05)。GAQ1在治疗后肯定回答率为86.7%;GAQ2在治疗后肯定回答率为80.2%;治疗期间无严重不良反应发生。结论每日1次小剂量PDE5i持续服用可以有效治疗糖尿病ED患者,而且耐受性良好,无明显不良反应,同时可以替代按需服用。     

仙鹿口服液联合西地那非治疗男性勃起功能障碍的疗效观察

目的 探讨仙鹿口服液联合西地那非治疗勃起功能障碍的临床疗效.方法 选取2019年8月—2020年9月河南省中医院接诊的120例男性勃起功能障碍患者,随机分为对照组和治疗组,每组各60例.对照组在性生活0.5～4 h前口服枸橼酸西地那非片,50 mg/次,1次/d;治疗组在对照组治疗基础上口服仙鹿口服液,10 mL/次,...     

前列地尔治疗糖尿病患者勃起功能障碍的临床分析

目的探讨前列地尔治疗糖尿病患者勃起功能障碍的疗效。方法将90例糖尿病合并勃起功能障碍患者按就诊顺序随机分为观察组（45例,伐地那非＋前列地尔）和对照组（45例,伐地那非）,疗程3月,比较两组阴茎的硬度、勃起时间、IIEF-5评分情况。结果观察组与对照组比较,阴茎的硬度满意度（29％VS18％）、勃起时间[（5．6±1．2）分VS（1．2±0．6）分]、IIEF-5评分[（22．1±2．3）分VS（17．5±1．9）分],观察组均有明显升高（P〈0．05,差异具有统计学意义）;观察组有3例发生不良反应,其中面色潮红2例、静脉炎1例。结论在伐地那非基础上加用前列地尔治疗可进一步改善糖尿病合并勃起功能障碍患者的勃起功能,且不良反应少。