Efficacy Of Sildenafil In Patients Research Articles

Effects of sildenafil on symptoms and exercise capacity for heart failure with reduced ejection fraction and pulmonary hypertension (the SilHF study): a randomized placebo-controlled multicentre trial.

AimsPulmonary hypertension (PHT) may complicate heart failure with reduced ejection fraction (HFrEF) and is associated with a substantial symptom burden and poor prognosis. Sildenafil, a phosphodiesterase‐5 (PDE‐5) inhibitor, might have beneficial effects on pulmonary haemodynamics, cardiac function and exercise capacity in HFrEF and PHT. The aim of this study was to determine the safety, tolerability, and efficacy of sildenafil in patients with HFrEF and indirect evidence of PHT.Methods and resultsThe Sildenafil in Heart Failure (SilHF) trial was an investigator‐led, randomized, multinational trial in which patients with HFrEF and a pulmonary artery systolic pressure (PASP) ≥40 mmHg by echocardiography were randomly assigned in a 2:1 ratio to receive sildenafil (up to 40 mg three times/day) or placebo. The co‐primary endpoints were improvement in patient global assessment by visual analogue scale and in the 6‐min walk test at 24 weeks. The planned sample size was 210 participants but, due to problems with supplying sildenafil/placebo and recruitment, only 69 patients (11 women, median age 68 (interquartile range [IQR] 62–74) years, median left ventricular ejection fraction 29% (IQR 24–35), median PASP 45 (IQR 42–55) mmHg) were included. Compared to placebo, sildenafil did not improve symptoms, quality of life, PASP or walk test distance. Sildenafil was generally well tolerated, but those assigned to sildenafil had numerically more serious adverse events (33% vs. 21%).ConclusionCompared to placebo, sildenafil did not improve symptoms, quality of life or exercise capacity in patients with HFrEF and PHT.

A meta-analysis on efficacy and tolerability of sildenafil for erectile dysfunction in patients with diabetes mellitus.

Erectile dysfunction (ED) is a common complication in patients with diabetes mellitus (DM). Sildenafil, a phosphodiesterase-5 inhibitor, is commonly used in patients with ED. This meta-analysis was planned to determine the strength of evidence to assess the efficacy and tolerability of sildenafil in patients with DM-associated ED. Electronic searches were carried out to identify randomized controlled trials (RCTs) which reported clinical efficacy of sildenafil in patients with DM-associated ED. Data were extracted and methodological quality was assessed. Relative Risk (RR) with 95% confidence intervals (CIs) was estimated for the dichotomous outcomes, and the mean difference with 95% CI was estimated for continuous data. Eight randomized controlled trials (RCTs) involving 1172 patients met with our inclusion criteria. In comparison to placebo, sildenafil significantly improved the overall sexual performance in patients of ED associated with DM with relative risk (RR) of answering “yes” to global efficiency question being 3.99 (95% CI: 2.58–6.18) compared to placebo. The rate of discontinuation due to treatment-related adverse reactions was 2.4% in sildenafil arm with RR of 2.67 (95% CI: 0.74–9.62). Sildenafil is an effective and safe medication for the treatment of ED associated with DM.

Polymorphism of the G Protein β3 Subunit Gene Influences the Efficacy of Sildenafil in Patients with Pulmonary Hypertension

The C825T polymorphism in the G protein β3 subunit gene (GNB3) influences the efficacy of sildenafil in patients with erectile dysfunction. The effects of this polymorphism on the therapeutic response to sildenafil in patients with pulmonary hypertension remains unknown. To investigate whether the GNB3C825T polymorphism is associated with the clinical efficacy of sildenafil in patients with pulmonary hypertension. Fifty-nine patients (age: 55.6 ± 13.3 [SD] yrs., mean pulmonary arterial pressure (Ppa): 52 ± 11 mmHg) with pulmonary arterial hypertension or chronic thromboembolic pulmonary hypertension were treated with sildenafil. The pre- and post-treatment parameters, including pulmonary hemodynamics measured using right heart catheterization, the systolic pulmonary arterial pressure estimated on Doppler echocardiography (sPA), the six-minute walk distance (6MWD) and freedom from clinical worsening, were compared between the patients with the TT and CT/CC genotypes. The pretreatment parameters were not significantly different between the two groups, with the exception of a lower mean Ppa in the TT group. The post-treatment World Health Organization (WHO) class was significantly better (p=0.03) and the 6MWD values trended toward improvement in the TT genotype patients compared with that observed in the CC/CT genotype patients (p=0.05). The time to clinical worsening was significantly longer in the TT genotype patients than in the CC/CT genotype patients (3-year freedom from clinical worsening: 83.1% vs. 46.0%, p=0.02), while the TT genotype was found to be a significant predictor of freedom from clinical worsening, even after adjusting for the baseline mean Ppa. The GNB3 C825T polymorphism influences the efficacy of sildenafil in patients with pulmonary hypertension.

Cigarette Smoking Is An Independent Predictor of Chronic Pain In Sickle Cell Patients: Results From the Walk-PHaSST Study

AbstractAbstract 4804 Introduction:Smoking is known to promote vascular inflammation, in-vitro platelet aggregation and expression of endothelial adhesion molecules, processes that contribute to vasculopathy. Inflammation, abnormal platelet activation with thrombus formation and endothelial cell activation also play a role in vaso-occlusion in sickle cell disease (SCD). These overlapping pathobiological mechanisms suggest the possibility of a relationship between smoking and SCD vaso-occlusive pain. While small single center studies have suggested a link between environmental smoke exposure and hospitalization rate for acute chest syndrome and SCD pain (West et al 2003, Cohen et al 2010) there is a paucity of data derived from large multicenter studies about the interplay between smoking and pain phenotype in SCD. Aims:To determine the relationship between patient self reported chronic pain and history of current or former cigarette smoking in the SCD subjects screened in the walk-PHaSST study. Methods:Walk-PHaSST was a multi-center, placebo-controlled, double-blind 16-week trial designed to evaluate the safety and efficacy of sildenafil in patients with tricuspid regurgitant velocity [TRV] ≥2.7m/s and decreased exercise capacity as assessed by the six-minute walk distance (6MWD).We analyzed the data from all subjects screened for the walk-PHaSST trial. In the screening trial, subjects were evaluated by medical history, physical examination, laboratory screening, echocardiography and 6MWD testing.Univariate and stepwise multivariable logistic regression was used for this analysis. P value of <0.05 was considered statistically significant. Results:Of the 720 patients screened, medical history on pain and smoking was obtained in a total of 673 subjects. Of these, 483/673 subjects (72%) had HbSS disease and 137 (20.4%) had HbSC disease. Mean age was 36.6 years (median 36.1 years).A total of 104 (15.5%) were current smokers and 114 (17.4%) reported having smoked in the past and 451 (67.1%) subjects reported no history of any life-time or current smoking. Subjects had smoked for a mean of 11.5 years (median 9 years, range 1–42 years). The mean pack years of smoking were 8.8 (median 5 years, range <1- 60 pack years).In a multivariable logistic regression model, being a ‘current’ cigarette smoker was associated with an increased odds ratio (OR 3.0, 95% CI 1.8–4.9) (See Table 1) of reporting chronic SCD pain as compared to no smoking history when adjusted for 1) self reported acute pain, 2) age, 3) gender, 4) hematocrit 4) marijuana use, 5) SCD genotype and 6) current hydroxyurea treatment.Additionally, in the multivariable model, being a ‘former’ cigarette smoker was associated with a smaller effect size (OR 2.2, 95% CI 1.4–3.5) of reporting chronic SCD pain as compared with no smoking history when adjusted for the above listed variables.On examining by SCD genotypes, the effect size was similar for HbSS genotype (OR 2.79, 95% CI: 1.54–5.0) while the effect size was significantly higher for HbSC genotype (OR 5.6, 95% CI: 1.7–19.0).The increase in self reported pain with number of pack years adjusted for age was not statistically significant although an increase in reported pain was observed with increase in the number of pack years (See Figure 1). Conclusions:These data suggest that being a current or former smoker is independently associated with ‘self reported chronic SCD pain’ after adjusting for potential confounding variables including age of the patient, gender, hematocrit, marijuana use and being on hydroxyurea treatment.However, it is unclear whether smoking might worsen pain, represent a stress relieving behavior by patients to chronic pain or even provide a beneficial adaptation to chronic pain mediated by nicotine, carbon monoxide, nitric oxide, or other substances known to be present in tobacco smoke. These data provide a rationale for further mechanistic studies of the relationship between smoking and chronic pain in patients with SCD.Table 1:Odds Ratio Estimates: Multivariable AnalysisEffectODDS RATIO Point Estimate95% Wald Confidence LimitsSMOKING Current smoker vs None3.01.85.0SMOKING Former smoker vs None2.21.43.5Age (per 10 yrs increment)1.31.11.5Gender: Female vs Male1.30.91.9Marijuana Use1.30.82.1SS vs Sß01.30.27.8SC vs Sß01.70.311.0Sß+ vs Sß02.50.318.3Hematocrit1.01.01.0Current Hydroxyurea Use0.80.51.1 [Display omitted] Disclosures:Hassell: Novartis: Research Funding. Barst: Pfizer: Consultancy, Research Funding. Rosenzweig: Pfizer: Research Funding. Badesch: Pfizer: Honoraria, Research Funding.

Safety and Efficacy of Transition From Subcutaneous Treprostinil to Oral Sildenafil in Patients With Pulmonary Arterial Hypertension

Sildenafil is a selective inhibitor of phosphodiesterase type 5 (PDE5), and has been shown to improve 6-minute walk distance (SMWD) and World Health Organization (WHO) functional class in patients with idiopathic pulmonary arterial hypertension (iPAH) and PAH associated with connective tissue disease or with repaired congenital systemic-to-pulmonary shunts. Despite the efficacy of sildenafil in patients on conventional therapy with diuretics and anti-coagulants, little is known of the safety and efficacy of transitioning patients already established on parenteral prostanoid therapy to sildenafil. We studied 14 patients on long-term subcutaneous treprostinil for PAH (from a cohort of 51 patients [27%]), who wished to discontinue treatment because of injection-site pain. The etiology of their PAH included iPAH (7 of 14), PAH secondary to scleroderma (2 of 14), thromboembolic disease (3 of 14) and PAH post-surgical correction of ventricular septal defect (2 of 14). Treprostinil was gradually weaned and all patients were started open-label with 50 mg sildenafil four times per day for 3 months. New York Heart Association (NYHA) functional class, SMWD, echocardiogram and quality-of-life (QOL) measures were determined at baseline and after 3 months of therapy with sildenafil. Of 14 patients, 4 discontinued the transition because of deterioration during treprostinil withdrawal, despite the introduction of sildenafil. Replacement of chronic subcutaneous treprostinil with sildenafil was possible in 10 of 14 patients (71%), who demonstrated stable NYHA class (mean +/- SD: 3.1 +/- 0.3 at baseline to 2.6 +/- 0.8 at 3 months, p = 0.138), stable SMWD (434 +/- 83 m at baseline, 451 +/- 72 at 3 months, p = 0.23) and significantly improved QOL measures at 3 months. The transition from subcutaneous treprostinil to sildenafil was safely achieved in most (71%), but not all, patients with pulmonary arterial hypertension of varied etiology. These patients had an improvement in both NYHA functional class and QOL, and maintained stable walk distances over a 3-month period on sildenafil therapy.

Sexual Function in Chronic Kidney Disease

Endocrine abnormalities are common in patients with chronic kidney disease (CKD) and lead to sexual dysfunction, anemia, hyperparathyroidism, and altered mineral metabolism. Common clinical problems include disturbances in menstruation in women, erectile dysfunction in men, and decreased libido and infertility in both sexes. Organic factors tend to be prominent and are related to uremia and other comorbid illnesses. Psychological factors and depression may exacerbate the primary problem. Alterations in the hypothalamic-pituitary axis are seen early in CKD and tend to worsen after patients start dialysis. Hypogonadism plays a dominant role in male sexual function, whereas changes in hypothalamic-pituitary function predominate in female sexual dysfunction. In patients on dialysis, treatment strategies include optimizing dose of dialysis, correction of anemia with erythropoietin, and correction of hyperparathyroidism. Successful kidney transplantation may restore normal sexual function, especially in younger patients.

Clinical Efficacy of Sildenafil in Patients With Pulmonary Hypertension in Functional Class II or III

To assess the efficacy of treatment with sildenafil monotherapy in patients with pulmonary hypertension.An observational study was undertaken in 11 patients with pulmonary hypertension in functional class II or III who received treatment with sildenafil (150 mg/day). Seven of the patients had inoperable chronic thromboembolic pulmonary hypertension and 4 had pulmonary arterial hypertension. To assess treatment response, the following parameters were assessed during follow-up at 3, 6, and 12 months: exercise tolerance in the 6-minute walk test, change in functional class, and systolic pulmonary arterial pressure measured by echocardiography.We observed a significant improvement in exercise tolerance, as shown by increased 6-minute walk distance after 3, 6, and 12 months of treatment (increases of 20, 67, and 95 m, respectively). All patients showed an improvement in functional class. The results of echocardiography did not reveal statistically significant differences in systolic pulmonary arterial pressure between baseline and 6 or 12 months of treatment. No significant adverse effects were observed, although sildenafil treatment was suspended in 1 patient due to persistent headache.The results of this study confirm that sildenafil is an effective drug for the management of pulmonary arterial hypertension and inoperable chronic thromboembolic pulmonary hypertension both in the short term and medium to long term, and that the drug is well tolerated and shows few side effects.

Phosphodiesterase 5 Inhibition in Chronic Heart Failure and Pulmonary Hypertension

Erectile dysfunction (ED) is highly prevalent in patients with chronic heart failure (CHF) and is among the most distressing symptoms in this patient population. Although the safety and efficacy of phosphodiesterase 5 (PDE5) inhibitors in the management of ED have been evaluated in many cardiovascular disease populations, scant data are available in patients with CHF. In published studies, the short-term safety and efficacy of sildenafil in patients with stable mild-to-moderate CHF with ED appears to be comparable to that observed in other populations with cardiovascular disease. Evidence is not available on the effects of vardenafil or tadalafil in CHF. In addition to their benefits in the treatment of ED, preliminary studies suggest that PDE5 inhibitors enhance endothelial function in patients with CHF and have beneficial effects on pulmonary hemodynamics and exercise capacity in patients with pulmonary hypertension. Additional studies are needed to determine the therapeutic potential of this class of agents in these disease states.

Efficacy of sildenafil in male dialysis patients with erectile dysfunction unresponsive to erythropoietin and/or testosterone treatments

The aim of this study was to evaluate the effects of recombinant human erythropoietin (Epo), testosterone (T) or a combination of them in the treatment of erectile dysfunction (ED) in hemodialysis patients, as well as the efficacy of sildenafil in patients unresponsive to combination treatment. A total of 23 patients with ED were divided into two groups. The international index of erectile function (IIEF) was used to evaluate ED and treatment response. Patients received Epo or T treatments for 12 weeks. Later on both groups received combination treatment for another 12 weeks. Although IIEF scores increased significantly in both groups after the combination treatment, the score changes were similar. After combination treatment, 16 patients still having IIEF score <26 were given sildenafil treatment in combination with Epo while T was discontinued. Although the IIEF scores increased significantly in all patients (17.4%), only eight of them attained an IIEF score of > or =26. The baseline IIEF scores of the patients with satisfactory response to the sildenafil treatment were higher than those with unsatisfactory response. The patients with a score of > or =22 responded better to the treatment. Although Epo and/or T therapies could partially improve ED in male dialysis patients besides correcting renal anemia and hypogonadism, sildenafil treatment could improve ED in unresponsive patients. Especially, those with higher baseline IIEF scores benefited more.

Assessment of the efficacy and safety of Viagra® (sildenafil citrate) in men with erectile dysfunction during long-term treatment

Long-term efficacy and safety of sildenafil was assessed in 1008 patients with erectile dysfunction (ED) enrolled in four flexible-dose (25 - 100 mg), open-label, 36- or 52-week extension studies. After 36 and 52 weeks, 92% and 89% of patients felt that treatment with sildenafil had improved their erections. Responses to a Sexual Function Questionnaire indicated that 52 weeks of sildenafil treatment resulted in clinically significant improvements in the duration and firmness of erections, overall satisfaction with sex life, and the frequency of stimulated erections. Commonly reported adverse events (AEs) were headache, flushing, dyspepsia, and rhinitis, which were generally mild to moderate. Reports of abnormal vision were consistent with previous clinical trials. The occurrence of treatment-related cardiovascular AEs, such as hypertension, tachycardia, and palpitation, was <1%. Discontinuations due to treatment-related AEs were low (2%). Long-term therapy does not diminish the efficacy of sildenafil in patients with ED and remains well tolerated.

Relative Efficacy of Sildenafil Compared to Other Treatment Options for Erectile Dysfunction

We examined and compared the efficacy of sildenafil in patients previously using other agents or devices for erectile dysfunction (ED) treatment.We identified 47 patients with organic ED who had tried other therapies (intracavernosal injection therapy [ICIT], intraurethral prostaglandin suppositories [IPS], vacuum erection devices [VEDs], or yohimbine) before using sildenafil. Comparisons of the efficacy of sildenafil to the previously used agent or device were assessed by telephone questionnaire. Responses were compared using nonparametric Wilcoxon rank sum and analysis of variance testing.Sildenafil therapy was no more effective than ICIT or VEDs but was more effective than IPS. No significant difference occurred in response to sildenafil with age. Of 22 patients achieving erections adequate for intercourse with their previous therapy, 14 (63%) achieved equal or improved erections with sildenafil. Of the remaining 18 patients who had erections inadequate for intercourse with previous therapy, 5 (27%) had adequate erections with sildenafil.Oral sildenafil therapy provides results comparable to those of other available ED treatment modalities. A trial of this drug in this patient population is warranted.

Relative Efficacy of Sildenafil Compared to Other Treatment Options for Erectile Dysfunction

We examined and compared the efficacy of sildenafil in patients previously using other agents or devices for erectile dysfunction (ED) treatment. We identified 47 patients with organic ED who had tried other therapies (intracavernosal injection therapy [ICIT], intraurethral prostaglandin suppositories [IPS], vacuum erection devices [VEDs], or yohimbine) before using sildenafil. Comparisons of the efficacy of sildenafil to the previously used agent or device were assessed by telephone questionnaire. Responses were compared using nonparametric Wilcoxon rank sum and analysis of variance testing. Sildenafil therapy was no more effective than ICIT or VEDs but was more effective than IPS. No significant difference occurred in response to sildenafil with age. Of 22 patients achieving erections adequate for intercourse with their previous therapy, 14 (63%) achieved equal or improved erections with sildenafil. Of the remaining 18 patients who had erections inadequate for intercourse with previous therapy, 5 (27%) had adequate erections with sildenafil. Oral sildenafil therapy provides results comparable to those of other available ED treatment modalities. A trial of this drug in this patient population is warranted.

Efficacy of Oral Sildenafil in Patients With Erectile Dysfunction After Radiotherapy for Carcinoma of the Prostate

Efficacy of Oral Sildenafil in Patients With Erectile Dysfunction After Radiotherapy for Carcinoma of the Prostate

Efficacy of Oral Sildenafil in Patients With Erectile Dysfunction After Radiotherapy for Carcinoma of the Prostate

Efficacy of Oral Sildenafil in Patients With Erectile Dysfunction After Radiotherapy for Carcinoma of the Prostate