vardenafil-dihydrochloride and Metabolic-Syndrome

Many men with erectile dysfunction (ED) also have associated underlying cardiovascular and metabolic conditions, for which they are likely to be taking medication. Therefore, cardiovascular safety and potential drug interactions are two of the major concerns when using PDE-5 inhibitors in these patients. The PDE-5 inhibitor, vardenafil, is characterized by a rapid onset of action, increased duration of erection, high rates of first-dose success and reliable efficacy that can be maintained with continued use. In both clinical trials and real-life observational studies, vardenafil has demonstrated a favorable efficacy and safety profile in men with ED, including those with associated underlying conditions such as diabetes, hypertension and dyslipidemia. Importantly, the concomitant use of medication for these conditions is not associated with any noteworthy changes in the efficacy and safety of vardenafil. The evidence presented in this review supports the use of vardenafil as a first-line treatment for men with ED, including those with underlying conditions.

Topics: Aging; Cardiovascular Diseases; Clinical Trials as Topic; Diabetes Complications; Drug Interactions; Erectile Dysfunction; Humans; Imidazoles; Male; Metabolic Syndrome; Phosphodiesterase Inhibitors; Piperazines; Prevalence; Risk Factors; Sulfones; Triazines; Vardenafil Dihydrochloride

The prevalence of erectile dysfunction (ED) is increased in men with metabolic syndrome compared with the general population.. The aim of this study was to evaluate the efficacy and safety of vardenafil vs. placebo in men who had ED and metabolic syndrome.. This was a 12-week, double-blind, randomized, multicenter, parallel-group, placebo-controlled prospective study in men with ED and metabolic syndrome (assessed by the International Diabetes Federation criteria). Vardenafil was administered at a starting dose of 10 mg, which could be titrated to 5 mg or 20 mg after 4 weeks, depending on efficacy and tolerability.. Primary efficacy measures were the erectile function domain of the International Index of Erectile Function (IIEF-EF) and Sexual Encounter Profile (SEP) diary questions 2/3. Secondary efficacy measures included SEP1, a diary question assessing ejaculation, the percentage of men achieving "return-to-normal" erectile function, and the percentage of men who titrated to a different dose. Adverse events (AEs) were recorded throughout the study.. The intent-to-treat population included 145 men (vardenafil, N = 75; placebo, N = 70). Baseline least squares IIEF-EF domain scores were low (vardenafil: 12.0; placebo: 12.7), indicative of moderate-to-severe ED. Vardenafil was statistically significantly superior to placebo for all primary efficacy measures (P < 0.0001) and showed nominally statistically significant superiority compared with placebo for SEP1/ejaculation success rates (P = 0.0003 and P < 0.0001, respectively) and the percentage of subjects reporting "return-to-normal" erectile function (P = 0.0004). Treatment-emergent AEs were mild-to-moderate in severity and consistent with the known AE profile of phosphodiesterase type 5 inhibitors.. This is the first study to assess the efficacy and safety of vardenafil, taken alone, for ED therapy in a population of men who all had metabolic syndrome. Although baseline erectile function in these patients was low, vardenafil treatment was associated with significant improvements in erectile function and rates of successful intercourse, and was well tolerated.

Topics: Adult; Aged; Erectile Dysfunction; Humans; Imidazoles; Male; Metabolic Syndrome; Middle Aged; Phosphodiesterase 5 Inhibitors; Piperazines; Sulfones; Treatment Outcome; Triazines; Vardenafil Dihydrochloride

Dyslipidemia occurs often in subjects with erectile dysfunction (ED), but there is little information about how this condition affects ED treatment responses.. To determine whether low-density lipoprotein cholesterol (LDL-C) levels, total cholesterol (TC)/high-density lipoprotein cholesterol (HDL-C) ratio; or the presence of metabolic syndrome influenced efficacy of vardenafil in men with ED and dyslipidemia.. Post hoc subgroup analysis of a 12-week study of the influence of lipid levels and presence of metabolic syndrome on the efficacy of vardenafil as measured by International Index of Erectile Function-Erectile Function (IIEF-EF) domain score, responses to Sexual Encounter Profile (SEP) SEP2 and SEP3 questions, duration of erection leading to successful intercourse, and erection duration regardless of the answer to SEP3. Lipid values were obtained at study start, after patients had received at least 3 months of therapy with a statin.. Outcomes in subjects with LDL-C < 100, > or = 100 to < 130, or > or = 130 mg/dL [< 2.59, > or = 2.59 to < 3.36, or > or = 3.36 mmol/L]; TC/HDL-C ratio < 3.5 vs. > or = 3.5, and presence or absence of metabolic syndrome.. Vardenafil improved all endpoints evaluated compared with placebo in all subgroups, however, nominally significant treatment by subgroup interaction terms did not follow a distinct pattern. Increasing LDL-C (P = 0.033), but not TC/HDL-C ratio or metabolic syndrome, was associated with an increase in treatment response measured by the IIEF-EF domain score. Responses to SEP3 were nominally influenced by LDL-C levels (P = 0.019), but were not significantly influenced by TC/HDL-C ratio, or the metabolic syndrome. Only higher TC/HDL-C ratios (> or = 3.5) were associated with larger treatment differences in duration of erection leading to successful intercourse (P = 0.028).. Vardenafil was effective in men with dyslipidemia regardless of LDL-C levels, TC/HDL-C ratio, and/or presence of metabolic syndrome. Despite the known presence of ED and dyslipidemia, other cardiovascular risk factors were apparently not aggressively managed.

Topics: Adult; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Double-Blind Method; Drug Therapy, Combination; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Imidazoles; Impotence, Vasculogenic; Male; Metabolic Syndrome; Middle Aged; Phosphodiesterase 5 Inhibitors; Phosphodiesterase Inhibitors; Piperazines; Sulfones; Treatment Outcome; Triazines; Vardenafil Dihydrochloride

A pathogenic link between erectile dysfunction (ED) and metabolic syndrome (MetS) is now well established. Nonalcoholic steatohepatitis (NASH), the hepatic hallmark of MetS, is regarded as an active player in the pathogenesis of MetS-associated cardiovascular disease (CVD). This study was aimed at evaluating the relationship between MetS-induced NASH and penile dysfunction. We used a non-genomic, high fat diet (HFD)-induced, rabbit model of MetS, and treated HFD rabbits with testosterone (T), with the selective farnesoid X receptor (FXR) agonist obeticholic acid (OCA), or with the anti-TNFα mAb infliximab. Rabbits fed a regular diet were used as controls. Liver histomorphological and gene expression analysis demonstrated NASH in HFD rabbits. Several genes related to inflammation (including TNFα), activation of stellate cells, fibrosis, and lipid metabolism parameters were negatively associated to maximal acetylcholine (Ach)-induced relaxation in penis. When all these putative liver determinants of penile Ach responsiveness were tested as covariates in a multivariate model, only the association between hepatic TNFα expression and Ach response was confirmed. Accordingly, circulating levels of TNFα were increased 15-fold in HFD rabbits. T and OCA dosing in HFD rabbits both reduced TNFα liver expression and plasma levels, with a parallel increase of penile eNOS expression and responsiveness to Ach. Also neutralization of TNFα with infliximab treatment fully normalized HFD-induced hypo-responsiveness to Ach, as well as responsiveness to vardenafil, a phosphodiesterase type 5 inhibitor. Thus, MetS-induced NASH in HFD rabbits plays an active role in the pathogenesis of ED, likely through TNFα, as indicated by treatments reducing liver and circulating TNFα levels (T or OCA), or neutralizing TNFα action (infliximab), which significantly improve penile responsiveness to Ach in HFD rabbits.

Topics: Acetylcholine; Animals; Antibodies, Monoclonal; Chenodeoxycholic Acid; Diet, High-Fat; Dietary Fats; Erectile Dysfunction; Fatty Liver; Gene Expression; Humans; Imidazoles; Infliximab; Liver; Male; Metabolic Syndrome; Non-alcoholic Fatty Liver Disease; Penis; Phosphodiesterase 5 Inhibitors; Piperazines; Rabbits; Receptors, Cytoplasmic and Nuclear; Sulfones; Testosterone; Triazines; Tumor Necrosis Factor-alpha; Vardenafil Dihydrochloride