Efficacy and safety of sildenafil in men with serotonergic antidepressant-associated erectile dysfunction: results from a randomized, double-blind, placebo-controlled trial. Efficacy of oral sildenafil in hemodialysis patients with erectile dysfunction. The efficacy and tolerability of sildenafil in patients with moderate-to-severe pulmonary hypertension. Sildenafil citrate for the treatment of erectile dysfunction in men with Type II diabetes mellitus. [Efficacy and safety of sildenafil in men with type 2 diabetes mellitus and erectile dysfunction]. The use of sildenafil in persistent pulmonary hypertension of the newborn. Effects of sildenafil and vardenafil on erectile dysfunction and health-related quality of life in haemodialysis patients: a prospective randomized crossover study. Randomized, controlled trial of long-term moderate exercise training in chronic heart failure: effects on functional capacity, quality of life, and clinical outcome. Oral sildenafil in infants with persistent pulmonary hypertension of the newborn: a pilot randomized blinded study.
To evaluate the efficacy of short-term treatment with sildenafil citrate in men with serotonin reuptake inhibitor (SRI)-associated erectile dysfunction (ED).
                Men (aged>or=18 years) with major depressive disorder (MDD; DSM-IV criteria) in remission and taking SRIs who experienced SRI-associated ED were enrolled in this multicenter, 6-week, randomized, flexible-dose, double-blind, placebo-controlled trial. The primary study measures were questions 3 (Q3: frequency of penetration) and 4 (Q4: frequency of maintained erections after penetration) of the International Index of Erectile Function (IIEF) questionnaire. Secondary study measures were all other questions and domains of the IIEF, the Erectile Dysfunction Index of Treatment Satisfaction (EDITS), a global efficacy questionnaire (GEQ), and a patient-maintained event log of sexual activity.
                Patients receiving sildenafil (N=71) versus placebo (N=71) reported significantly higher mean+/-SE scores on Q3 (3.9+/-0.2 vs. 3.1+/-0.2, p=.003) and Q4 (3.7+/-0.2 vs. 2.8+/-0.2, p<.001) of the IIEF and significantly higher scores on all domains of the IIEF. Patients receiving sildenafil also reported significantly improved scores on all questions of the EDITS questionnaire (p<.02) and the GEQ (p<.0001) and an increased number of successful sexual intercourse attempts per week (p<.0001) compared with patients receiving placebo. All patients remained in MDD remission (score<or=10 on the Hamilton Rating Scale for Depression). Adverse events in patients taking sildenafil (vs. placebo) were headache (9% vs. 9%), dyspepsia (9% vs. 1%), anxiety (6% vs. 4%), and abnormal vision (3% vs. 0%).
                Short-term (6-week) administration of sildenafil was well tolerated and significantly improved erectile function and overall sexual satisfaction in men with ED associated with SRI therapy for MDD. Sildenafil may be successfully used to treat SRI-associated ED without interruption of antidepressant therapy. The aim of this study was to evaluate the efficacy and safety of oral sildenafil to treat erectile dysfunction (ED) in chronic renal failure in patients on hemodialysis (HD). A double-blind, randomized, placebo-controlled study of oral sildenafil (50 mg) administered as required in HD patients with ED was designed. Patients on HD for at least 6 mo and who had a stable relationship with a female sexual partner were included. Patients older than 70 yr with penile anatomic abnormalities, cirrhosis, diabetes, angina, severe anemia, and those who were on nitrate treatment or with a recent history of stroke or myocardial infarction were not included. The International Index of Erectile Dysfunction (IIEF) was employed to evaluate ED and treatment response. Forty-one patients were evaluated (21 received placebo, and 20 sildenafil). Baseline clinical and demographic parameters were similar in both groups. Sildenafil was associated with improvement in the score of all questions and domains of the IIEF, except those related to sexual desire. Using the erectile function domain to evaluate primary efficacy, improvement was observed in 85% of the sildenafil patients compared with 9.5% of placebo patients. Sildenafil use resulted in normal EF scores in 35% of sildenafil patients. Sildenafil was well tolerated. Headaches and flushing occurred in both groups. Dyspepsia was reported by two patients in the sildenafil group. In conclusion, oral sildenafil seems to be an effective and safe treatment for ED in selected patients with chronic renal failure on hemodialysis. Pulmonary arterial hypertension is a life-threatening disease for which continuous intravenous infusion of prostacyclin has proved effective. However, it carries the risk of serious complications arising from the complex delivery system. Prostacyclin analogs, endothelin antagonists, and the phosphodiesterase-5 inhibitor sildenafil are emerging promising therapies. This study was aimed at evaluating the utility of oral sildenafil in patients with pulmonary hypertension of varied etiology, poorly controlled on conventional treatment.
                Ten consecutive patients with pulmonary hypertension, either primary or related to previous left-to-right shunts, thromboembolism, or interstitial lung disease, poorly controlled on conventional therapy such as warfarin, calcium antagonists, digitalis, and diuretics, were included. A thorough clinical, laboratory, and comprehensive echo Doppler evaluation was performed before enrollment in the trial to establish the diagnosis and obtain baseline data. Subjects received sildenafil 25 mg 8 hourly, or a matching placebo for two weeks each, in a randomized, double-blind, crossover design. A run-in period of two weeks was permitted between the two therapies during which patients continued to receive the conventional therapy without any vasodilator. At the end of each therapy period, the patients were evaluated for symptoms, New York Heart Association class, distance covered during the 6 min walk test, rating of modified Borg dyspnea score, and systolic pulmonary artery pressure using echo Doppler. The differences in the above variables at the end of sildenafil and placebo therapies were compared. Nine patients completed the study protocol. Sildenafil, compared to placebo, was associated with improved exercise tolerance as determined by the 6 min walk test (266.67+/-131.45 m v. 170+/-105 m; p<0.005), decrease in modified Borg dyspnea score (3.56+/-1.01 v. 5.11+/-1.45; p<0.01), decrease in Doppler-estimated pulmonary artery systolic pressures (55.33+/-16.52 mmHg v. 75.33+/-19.75 mmHg; p<0.005), improvement in New York Heart Association class (2 patients), and improvement in symptoms. Sildenafil was well tolerated with no untoward effects; further, no significant changes in heart rate or blood pressure occurred during the study period.
                Sildenafil improves exercise capacity and symptoms, and decreases pulmonary artery pressures in patients with primary or secondary pulmonary hypertension of varied etiology. Ninety percent of all men with diabetes have Type II (non-insulin-dependent) diabetes mellitus, and erectile dysfunction (ED) is common in this patient group. This study evaluated the effects of sildenafil on men with erectile dysfunction and Type II diabetes and compared the results with glycated haemoglobin concentrations and chronic diabetic complications.
                Patients (mean age, 59 years) in this double-blind, placebo-controlled trial were randomised to sildenafil (25-100 mg; n = 110) or matching placebo (n = 109) for 12 weeks. Primary criteria for efficacy included questions 3 (achieving an erection) and 4 (maintaining an erection) from the International Index of Erectile Function (IIEF, score range, 0-5). Secondary outcome measures included a global efficacy question (GEQ), patient event logs, a life satisfaction checklist, and the remaining IIEF questions.
                After 12 weeks, the mean scores for questions 3 and 4 had improved significantly in patients receiving sildenafil (3.42 +/- 0.23 and 3.35 +/- 0.24) compared with placebo (1.86 +/- 0.22 and 1.84 +/- 0.23; p < 0.0001). Similarly, the GEQ score was higher in the sildenafil (64.6 %) than the placebo group (10.5 %). Even when correlating efficacy with glycated haemoglobin concentrations ( < or = 8.3 % or > 8.3 %, the median concentration found in this study) or the number of diabetic complications (0 or > or = 1), the mean scores for the GEQ and questions 3 and 4 from the IIEF remained higher for all the sildenafil groups compared with the placebo groups (p < 0.0001).
                Sildenafil was well-tolerated and effective in improving erectile dysfunction in men with Type II diabetes, even in patients with poor glycaemic control and chronic complications. Erectile dysfunction is a common complication in patients with diabetes mellitus, which impairs quality of life, decreases self-esteem and can affect partners relationships. Sildenafil improves nitric oxide-dependent relaxation of smooth muscle in corpora cavernosa--induced by an increase in cGMP via inhibition of phosphodiesterase 5.
                Multicenter, randomized, double-blind, placebo-controlled study with flexible doses of sildenafil. The study was performed in 16 centers and recruited a total of 112 subjects with diabetes mellitus who had erectile dysfunction. At the start and end of the study, the following questionnaires were administered: International Index of Erectile Function (IIEF), Global Efficacy Assessment Question and Quality of Life Questionnaire (Fugl-Meyer). Of the 112 initially recruited patients, 92 received treatment, sildenafil in 44 and placebo in 48.
                A clear improvement was observed in the capacity to achieve and maintain an erection; 55.3% diabetic patients receiving sildenafil had at least one successful sexual intercourse (15.6% in the placebo group). In addition, significant improvements were seen in other aspects of the sexual activity of treated subjects. Among those treated with sildenafil, 46.3% reported a clear improvement of erections as compared to their baseline conditions (i.e, prior to treatment) vs only 14.9% in the placebo group. The percentage of a successful intercourse clearly increased, from 6 to 49%. Sildenafil was well-tolerated. Side effects were mild and transient.
                Sildenafil is an effective, safe treatment for erectile dysfunction in diabetic patients. We evaluated the effectiveness of sildenafil in the treatment of neonatal pulmonary hypertension. We performed a double-blind randomized clinical trial in 51 full-term infants with persistent pulmonary hypertension confirmed by Doppler echocardiography. Patients were divided in two groups: 20 infants in group A received placebo when the oxygenation index was >20, and 31 infants in group B received 3 mg/kg of oral sildenafil every 6 hours. Arterial blood gases were taken at 1, 4, 7, 13, 19, and 25 hours after treatment was started. Main outcome measures were oxygenation changes, time on mechanical ventilation, and mortality. Both groups were comparable in general variables as well as in illness severity. We observed better oxygenation parameters after 7 hours of sildenafil treatment, but no significant changes were found in the placebo group. Mortality was higher in the placebo group (40%) than in those infants who received sildenafil (6%; P = 0.004), although no difference was found in time on mechanical ventilation between groups. Our results confirm that sildenafil may be a useful adjuvant therapy for term infants with pulmonary hypertension in centers lacking inhaled nitric oxide and extracorporeal membrane oxygenation.
                Thieme Medical Publishers. Erectile dysfunction (ED) is prevalent in end-stage renal disease (ESRD) and has been associated with impaired health-related quality of life (HRQoL). HRQoL, in turn, is related to morbidity and mortality in ESRD patients. Previous studies have shown improved HRQoL with ED treatment using sildenafil and vardenafil. However, no study has examined the effects of sildenafil or vardenafil on HRQoL in impotent ESRD patients. Furthermore, vardenafil has never been tested and its safety profile has not been determined in ESRD patients. The aim of this randomized crossover study was to compare the effects of sildenafil and vardenafil on measures of HRQoL and on ED scores as well as to determine the safety profile of vardenafil in ESRD patients.
                In 32 haemodialysis patients with impotence, ED and HRQoL were evaluated by the International Index of Erectile Function (IIEF-5) and the 36-item Short-Form Health (SF-36) surveys, respectively. Patients were randomized into sildenafil and vardenafil groups. After a 4-week treatment and 2-week washout periods, crossover was performed and an additional 4-week treatment was administered. IIEF-5 and SF-36 surveys were given before and after each treatment period. Adverse effects were evaluated by interview. Friedman tests and Bonferroni-adjusted Wilcoxon signed-rank tests were used to compare groups and for post hoc analysis, respectively.
                IIEF-5 and SF-36 scores were significantly improved by both sildenafil and vardenafil compared to pretreatment values. There were no differences between sildenafil and vardenafil with respect to the studied parameters. Adverse effect profiles were also similar. No patient dropped out because of side effects.
                Sildenafil and vardenafil caused similar improvements in ED and HRQoL in haemodialysis patients. Vardenafil was well tolerated in our patient population. It is still a matter of debate whether exercise training (ET) is a beneficial treatment in chronic heart failure (CHF).
                To determine whether long-term moderate ET improves functional capacity and quality of life in patients with CHF and whether these effects translate into a favorable outcome, 110 patients with stable CHF were initially recruited, and 99 (59+/-14 years of age; 88 men and 11 women) were randomized into 2 groups. One group (group T, n=50) underwent ET at 60% of peak &f1;O2, initially 3 times a week for 8 weeks, then twice a week for 1 year. Another group (group NT, n=49) did not exercise. At baseline and at months 2 and 14, all patients underwent a cardiopulmonary exercise test, while 74 patients (37 in group T and 37 in group NT) with ischemic heart disease underwent myocardial scintigraphy. Quality of life was assessed by questionnaire. Ninety-four patients completed the protocol (48 in group T and 46 in group NT). Changes were observed only in patients in group T. Both peak &f1;O2 and thallium activity score improved at 2 months (18% and 24%, respectively; P<0. 001 for both) and did not change further after 1 year. Quality of life also improved and paralleled peak VO2. Exercise training was associated both with lower mortality (n=9 versus n=20 for those with training versus those without; relative risk (RR)=0.37; 95% CI, 0.17 to 0.84; P=0.01) and hospital readmission for heart failure (5 versus 14; RR=0.29; 95% CI, 0.11 to 0.88; P=0.02). Independent predictors of events were ventilatory threshold at baseline (beta-coefficient=0.378) and posttraining thallium activity score (beta-coefficient -0.165).
                Long-term moderate ET determines a sustained improvement in functional capacity and quality of life in patients with CHF. This benefit seems to translate into a favorable outcome. Persistent pulmonary hypertension (PPHN) occurs in as many as 6.8 of 1000 live births. Mortality is approximately 10% to 20% with high-frequency ventilation, surfactant, inhaled nitric oxide, and extracorporeal membrane oxygenation but is much higher when these therapies are not available. Sildenafil is a phosphodiesterase inhibitor type 5 that selectively reduces pulmonary vascular resistance.
                Our goal was to evaluate the feasibility of using oral sildenafil and its effect on oxygenation in PPHN.
                This study was a proof-of-concept, randomized, masked study in infants >35.5 weeks' gestation and <3 days old with severe PPHN and oxygenation index (OI) >25 admitted to the NICU (Hospital Niño Jesús, Barranquilla, Colombia). The sildenafil solution was prepared from a 50-mg tablet. The first dose (1 mg/kg) or placebo was given by orogastric tube <30 minutes after randomization and every 6 hours. Preductal saturation and blood pressure were monitored continuously. OI was calculated every 6 hours. The main outcome variable was the effect of oral sildenafil on oxygenation. Sildenafil or placebo was discontinued when OI was <20 or if there was no significant change in OI after 36 hours.
                Six infants with an OI of >25 received placebo, and 7 received oral sildenafil at a median age of 25 hours. All infants were severely ill, on fraction of inspired oxygen 1.0, and with similar ventilatory parameters. Intragastric sildenafil and placebo were well tolerated. In the treatment group, OI improved in all infants within 6 to 30 hours, all showed a steady improvement in pulse oxygen saturation over time, and none had noticeable effect on blood pressure; 6 of 7 survived. In the placebo group, 1 of 6 infants survived.
                Oral sildenafil was administered easily and tolerated as well as placebo and improved OI in infants with severe PPHN, which suggests that oral sildenafil may be effective in the treatment of PPHN and underscores the need for a large, controlled trial.
The validity of the observed effects is undermined by small participant numbers and inadequate exploration of the different disease etiologies. The effects on long term outcome such as NYHA functional class, symptoms, mortality and exercise capacity require further validation. More studies of adequate size are required before the long term effects of sildenafil on clinically important outcomes can be established.