vardenafil-dihydrochloride and Cardiovascular-Diseases

Erectile dysfunction is usually of vascular origin and is frequently encountered in men with cardiovascular disease. The introduction of phosphodiesterase-5 inhibitors has revolutionized the management of patients with erectile dysfunction. Currently available phosphodiesterase-5 inhibitors have distinct pharmacokinetic and pharmacodynamic properties, thus permitting for tailoring sexual therapy according to patient characteristics and needs. Phosphodiesterase-5 inhibitors possess vasorelaxing properties and exert systemic hemodynamic effects, which need to be taken into account when other cardiovascular drugs are co-administered. Special caution is needed with alpha-blockers, while the co-administration with nitrates is contra-indicated due to the risk of life-threatening hypotension. This review presents the advent of sexual therapy, describes the mechanism of action and the specific characteristics of commercially available phosphodiesterase-5 inhibitors, summarizes the efficacy and safety of these drugs with special emphasis on the cardiovascular system, and discusses the clinical criteria used for the selection of each drug for the individual patient.

Topics: Cardiovascular Diseases; Drug Incompatibility; Erectile Dysfunction; Humans; Male; Phosphodiesterase 5 Inhibitors; Sildenafil Citrate; Tadalafil; Vardenafil Dihydrochloride; Vasodilator Agents

Erectile dysfunction (ED) is a very common multidimensional disorder affecting men worldwide. Physical illness, reaction to life stresses, or an unhappy couple relationship influence clinical outcome. Phosphodiesterase type 5 (PDE5) inhibitors are recognized as efficacious and well tolerated, and are the first-line treatment for ED. Sildenafil, tadalafil, and vardenafil are the most widely used and studied PDE5 inhibitors. Data acquired during a routine diagnostic workup for ED should be taken into account when choosing the best PDE5 inhibitor for the individual patient, creating an individualized treatment plan, and going beyond "experience-based" subjective opinion and unfounded ideas and prejudice regarding currently available drugs.. As the process of matching a given patient's profile to any selected PDE5 inhibitor often relies more on physician's personal convictions than on solid evidence, the aim of this review is to identify the main clinical, demographic, and relational factors influencing the choice of the PDE5 inhibitor to be used for the treatment of ED.. A systematic literature search and current treatment guidelines were evaluated in a systematic manner.. The main clinical, cultural, and demographical factors to be considered for the treatment of ED have been identified.. Main factors influencing the choice of the treatment for ED have been described. A short list of items that may help in choosing the right PDE5 inhibitor for the treatment of different patients in daily clinical practice has been prepared.. The simple algorithms prepared should be a useful tool to be used in daily practice, which may help in choosing the right treatment for each subject affected by ED.

Topics: Algorithms; Carbolines; Cardiovascular Diseases; Diabetes Mellitus; Humans; Hypertension; Imidazoles; Impotence, Vasculogenic; Male; Men's Health; Phosphodiesterase 5 Inhibitors; Piperazines; Purines; Pyrimidines; Risk Factors; Sildenafil Citrate; Sulfonamides; Sulfones; Tadalafil; Triazines; Vardenafil Dihydrochloride

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

Vardenafil has demonstrated efficacy for the pharmacological management of erectile dysfunction (ED). Accumulating evidence suggests that ED is frequently associated with underlying cardiovascular and metabolic conditions which are thought to be involved in the aetiology of ED. The present review aims to summarise and discuss the available evidence for the efficacy, safety and tolerability of vardenafil in patients with underlying conditions including diabetes, hypertension and dyslipidaemia.. Relevant articles were identified through a PubMed search of clinical trials and postmarketing surveillance studies of vardenafil in patients with ED including those with diabetes, hypertension and dyslipidaemia.. Across all trials, vardenafil showed good efficacy for the treatment of ED in patients with diabetes, hypertension and dyslipidaemia. Vardenafil also showed a favourable safety and tolerability profile. The concomitant use of medication to treat hypertension or dyslipidaemia was not associated with an increase in adverse events following vardenafil treatment.. The prevalence of both diagnosed and undiagnosed underlying conditions is high among men with ED. The evidence presented in this review suggests that vardenafil is efficacious and well tolerated in patients with ED and diabetes, hypertension and/or dyslipidaemia and can be recommended as first-line treatment for ED in patients with these conditions.

Topics: Cardiovascular Diseases; Diabetes Complications; Dyslipidemias; Erectile Dysfunction; Humans; Hypertension; Imidazoles; Male; Phosphodiesterase Inhibitors; Piperazines; Randomized Controlled Trials as Topic; Sulfones; Treatment Outcome; Triazines; Vardenafil Dihydrochloride

Clinical evidence in men with erectile dysfunction (ED) shows that the phosphodiesterase type 5 (PDE5) inhibitors sildenafil citrate, tadalafil, and vardenafil hydrochloride have favorable safety and efficacy profiles. However, as mild vasodilators, the PDE5 inhibitors are also associated with hemodynamic effects that may be clinically significant, especially when treating men with ED who have comorbid cardiovascular disease. Hemodynamic studies have shown that therapeutic dosages of the PDE5 inhibitors produce only mild and transient changes in mean systolic and diastolic blood pressure and heart rate in healthy men as well as those with ischemic heart disease or chronic stable angina. Overall, PDE5 inhibitors are safe and effective in most patient populations, including men with ischemic cardiovascular disease or those receiving anti-hypertensive agents, and men with diabetes or those who have undergone nerve-sparing retropubic radical prostatectomy. With the entry of three novel PDE5 inhibitors into the therapeutic armamentarium for ED, differentiating properties of the new agents may confer clinical benefits that physicians as well as patients and their partners should consider when selecting a PDE5 inhibitor.

Topics: Antihypertensive Agents; Cardiovascular Diseases; Diabetes Complications; Drug Interactions; Erectile Dysfunction; Humans; Imidazoles; Male; Nitrates; Phosphodiesterase Inhibitors; Piperazines; Purines; Sildenafil Citrate; Sulfones; Treatment Outcome; Triazines; Vardenafil Dihydrochloride

Although vardenafil is widely prescribed for erectile dysfunction (ED), its effect on arterial function is not defined. Aortic stiffness, aortic pressures, and wave reflections are predictors of cardiovascular risk. The investigators assessed the hypothesis that vardenafil acutely improves aortic stiffness, aortic pressures, and wave reflections in ED patients. Twelve ED patients (mean age 58 ± 9 years) received vardenafil 20 mg in a randomized, placebo-controlled, double-blind, 2-way crossover design. Aortic stiffness was evaluated with carotid-femoral pulse wave velocity (PWV); wave reflections and aortic pressures were evaluated with augmentation index (AIx) and systolic, diastolic, and pulse pressure of the aortic pressure waveform, respectively. PWV, aortic pressures, and AIx were measured at baseline and for 3 hours after vardenafil intake or placebo. PWV decreased significantly (by 0.7 m/s, P = .001), denoting a decrease in aortic stiffness. AIx decreased significantly (by 7%, P = .008), denoting a decreased effect of wave reflections from the periphery. Aortic pressures decreased significantly (all P < .05). Statin use at baseline significantly interacted with the effects of treatment on both PWV and AIx (P = .003 and P < .001, respectively). This study shows, for the first time, that vardenafil has a favorable acute effect on aortic stiffness and wave reflection in ED patients.

Topics: Aorta; Arterial Pressure; Blood Pressure; Cardiovascular Diseases; Cross-Over Studies; Double-Blind Method; Erectile Dysfunction; Heart Rate; Humans; Imidazoles; Male; Middle Aged; Piperazines; Pulse Wave Analysis; Sulfones; Triazines; Vardenafil Dihydrochloride; Vascular Stiffness

Data from head-to-head clinical trials of phosphodiesterase type 5 (PDE5) inhibitors are scarce, making it difficult for clinicians to differentiate among these agents to select the most appropriate treatment for their patients with erectile dysfunction (ED).. This randomized, double-blind, crossover head-to-head clinical trial compared patient preference, efficacy, and safety of vardenafil and sildenafil in men with ED and diabetes, hypertension, and/or hyperlipidemia.. Prospective analysis was performed on two studies in which 1,057 men were randomized to vardenafil 20 mg (N = 530) or sildenafil 100 mg (2 x 50 mg encapsulated tablets) (N = 527) for 4 weeks. Following a 1-week washout, patients switched treatment for 4 weeks.. Patients were asked about overall preference: "Overall, which medication do you prefer?", plus 11 other preference questions relating to their ED treatment. Efficacy assessments after each treatment period included the erectile function (EF) domain score of the International Index of Erectile Function (IIEF); Sexual Encounter Profile (SEP) diary questions SEP2 and SEP3; Global Assessment Question (GAQ); and Treatment Satisfaction Scale (TSS). Data regarding adverse events were collected throughout the study.. A total of 931 men (mean age 57.9 years) were included in the intent-to-treat (ITT) population. Non-inferiority of vardenafil over sildenafil was achieved for overall preference (vardenafil 38.9%; sildenafil 34.5%; and no preference 26.6%). Additionally, the change from baseline in the EF domain score of the IIEF achieved nominal significance for vardenafil over sildenafil (10.00 vs. 9.40; P = 0.0052). Patients also had a higher percentage of positive responses for vardenafil for SEP2, SEP3, GAQ, and 12 of 19 questions on the TSS. Both drugs were well tolerated.. This randomized, double-blind, head-to-head trial in ED patients with cardiovascular risk factors demonstrated noninferiority of vardenafil for overall preference. Vardenafil achieved nominal statistical superiority over sildenafil for several frequently used efficacy measures. Both drugs were well tolerated.

Topics: Adult; Aged; Cardiovascular Diseases; Cross-Over Studies; Double-Blind Method; Erectile Dysfunction; Humans; Imidazoles; Male; Middle Aged; Patient Satisfaction; Phosphodiesterase Inhibitors; Piperazines; Purines; Severity of Illness Index; Sildenafil Citrate; Sulfones; Surveys and Questionnaires; Treatment Outcome; Triazines; Vardenafil Dihydrochloride; Vasodilator Agents

In recent years, there has been an increase in the use of phosphodiesterase type 5 inhibitors (PDE5i) that are purchased from abroad without a doctor's diagnosis via the Internet or other means. We report six cases in which nonprescription use of PDE5i may have led to death. Among the four deceased individuals who were believed to have experienced sudden cardiac death, three (cases 1-3) had a history of cardiovascular disease, which is a contraindication, and the remaining case (case 4) involved combined use of multiple PDE5i. Sildenafil (0.063 µg/mL, 0.087 µg/mL) was detected in two of the four cases of sudden cardiac death. Tadalafil (0.096 µg/mL) was detected in one of the remaining two cases, and tadalafil (0.197 µg/mL) and vardenafil (0.011 µg/mL) were detected in the other case. Sildenafil (0.032 µg/mL), tadalafil (0.062 µg/mL), and ethanol were detected in a traffic accident case with a history of contraindications. In a case of asphyxiation by vomit aspiration, autopsy showed 90% stenosis in the anterior descending branch of the coronary artery, and sildenafil (0.063 µg/mL) was detected. To the best of our knowledge, this is the first report of postmortem blood levels of tadalafil and vardenafil likely contributing to the cause of death. Despite all the warnings about the dangers of using PDE5 inhibitors, cases of PDE5i contributing to death are still identified during autopsies. Therefore, raising public awareness of the risks of the risks associated with the imported drug use by individuals is necessary.

Topics: Adult; Aged; Aged, 80 and over; Cardiovascular Diseases; Contraindications, Drug; Death, Sudden, Cardiac; Erectile Dysfunction; Forensic Medicine; Humans; Male; Middle Aged; Phosphodiesterase 5 Inhibitors; Risk; Sexual Behavior; Sildenafil Citrate; Tadalafil; Vardenafil Dihydrochloride

Endothelial dysfunction and vascular reactivity defects secondary to metabolic and immunological disorders carry risk of serious cardiovascular complications. Here, the effects of the phosphodiesterase (PDE) inhibitors vardenafil and cilostazol were examined against rheumatoid arthritis (RA)/diabetes mellitus (DM)-co-morbidity-induced endothelial dysfunction and vascular reactivity defects. After setting of RA/DM-co-morbidity model, rats were divided into a normal control group, an RA/DM-co-morbidity group, and two treatment groups receiving oral vardenafil (10 mg/kg/day) and cilostazol (30 mg/kg/day) for 21 days after RA/DM-co-morbidity induction. Aorta was isolated for biochemical estimations of the pro-inflammatory vasoconstrictor molecules angiotensin-II (Ang-II) and endothelin-1 (ET-1), the adhesion molecules P-selectin and vascular cell adhesion molecule-1 (VCAM-1), the energy sensor adenosine-5'-monophosphate-activated protein kinase (AMPK), and the vasodilator anti-inflammatory molecule vasoactive intestinal peptide (VIP) using enzyme-linked immunosorbent assay (ELISA) and western blot analysis. Immunohistochemical estimations of endothelial nitric oxide synthase (eNOS) and matrix metalloproteinase (MMP)-2 were performed coupled with histopathological examination using routine hematoxylin and eosin (H&E) and special Masson trichrome staining. The in vitro study was conducted using aortic strips where cumulative concentration response curves were done for the endothelium-dependent relaxing factor acetylcholine and the endothelium-independent relaxing factor sodium nitroprusside after submaximal contraction with phenylephrine. Vardenafil and cilostazol significantly improved endothelial integrity biomarkers in vivo supported with histopathological findings in addition to improved vasorelaxation in vitro. Apart from their known PDE inhibition, up-regulation of vascular AMPK and eNOS coupled with down-regulation of Ang-II, ET-1, P-selectin, VCAM-1 and MMP-2 may explain vardenafil and cilostazol protective effect against RA/DM-co-morbidity-induced endothelial dysfunction and vascular reactivity defects.

Topics: Animals; Arthritis, Experimental; Arthritis, Rheumatoid; Cardiovascular Diseases; Cilostazol; Comorbidity; Diabetes Mellitus, Experimental; Endothelium, Vascular; Female; Rats; Vardenafil Dihydrochloride; Vasodilator Agents

Appropriate algorithms for the prediction of cardiovascular risk are strongly suggested in clinical practice, although still controversial. In type 2 diabetes mellitus (T2DM), the beneficial effect of phosphodiesterase (PDE)-5 inhibitors is demonstrated on endothelial function but not on the estimation of cardiovascular risk.. To study whether the chronic Vardenafil administration to men with T2DM influences variables correlated with the predicted long-term cardiovascular risk calculated by different validated algorithms.. Per-protocol analysis of a longitudinal, prospective, randomized, placebo-controlled, double-blind, investigator-started, clinical trial. 54 male patients affected by T2DM were assigned to study (26patients) and control-group (28patients), respectively. The study included a treatment phase (24weeks) (Vardenafil/placebo 10mg twice-daily) and a follow-up phase (24weeks). Three time points were considered: baseline(V0), end of treatment(V1) and end of the study(V2). Parameters evaluated: endothelial health-related parameters and cardiovascular risk, assessed by calculating the Framingham (coronary hart disease [CHD], myocardial infarction [MI], stroke and cardiovascular disease [CVD]), ASSIGN and CUORE equations.. Predicted cardiovascular risk at ten years resulted different using the three algorithms chosen, without differences between study and control groups and among visits. IL-6 was directly related to CHD, CVD and CUORE scores at V1 and with MI and STROKE at V2. Similarly, hs-CRP was directly related to CHD, MI, STROKE and CUORE only at V1 in the study group. Testosterone serum levels were inversely related to CHD and MI at V1 in study group.. The predicted cardiovascular risk is different depending on the algorithm chosen. Despite no predictive risk reduction after six months of treatment, a possible effect of Vardenafil could be hypothesized through its action on inflammation markers reduction and through restoration of normal testosterone levels.

Topics: Cardiovascular Diseases; Diabetes Mellitus, Type 2; Endothelium; Gonads; Humans; Longitudinal Studies; Male; Reproducibility of Results; Retrospective Studies; Risk Assessment; Risk Factors; Vardenafil Dihydrochloride

To ensure public safety all Food and Drug Administration (FDA)-approved medications undergo postapproval safety analysis. Phosphodiesterase type-5 inhibitors (PDE5-i) are generally regarded as safe and effective.. We performed a nonindustry-sponsored analysis of FDA reports for sildenafil, tadalafil, and vardenafil to evaluate the reported cardiovascular and mortality events over the past 10 years.. Summarized reports of adverse events (AEs) for each PDE5-i were requested from the Center for Drug Evaluation and Research within the FDA. These data are available under the Freedom of Information Act and document industry and nonindustry reports of AEs entered into the computerized system maintained by the Office of Surveillance and Epidemiology.. The data were analyzed for the number of AE reports, number of objective cardiovascular events, and reported deaths.. Overall, 14,818 AEs were reported for sildenafil. There were 1,824 (12.3%) reported deaths, and reports of cardiovascular AEs numbered 2,406 (16.2%). Tadalafil was associated with 5,548 AEs and 236 deaths were reported. Vardenafil was associated with 6,085 AEs and 121 reports of deaths. The percentage of reported severe cardiovascular disorders has stabilized at 10% to 15% of all AE reports for sildenafil and tadalafil and 5% to 10% for vardenafil. Only 10% of AE reports sent to the FDA for PDE5-i were from pharmaceutical manufacturers.. Reports of deaths associated with PDE5-i remain around 5% of total reported events. Despite inherent limitations from evaluating FDA reports of AEs, it is important that these reports be reviewed outside pharmaceutical industry support in order to provide due diligence and transparency. Lowe G and Costabile RA. 10-year analysis of adverse event reports to the Food and Drug Administration for phosphodiesterase type-5 inhibitors. J Sex Med 2012;9:265-270.

Topics: Carbolines; Cardiovascular Diseases; Erectile Dysfunction; Humans; Imidazoles; Male; Phosphodiesterase 5 Inhibitors; Piperazines; Product Surveillance, Postmarketing; Purines; Sildenafil Citrate; Sulfones; Tadalafil; Triazines; United States; United States Food and Drug Administration; Vardenafil Dihydrochloride

Topics: Blood Glucose; Carbolines; Cardiovascular Diseases; Cholesterol; Erectile Dysfunction; Humans; Imidazoles; Impotence, Vasculogenic; Male; Middle Aged; Phosphodiesterase 5 Inhibitors; Phosphodiesterase Inhibitors; Piperazines; Purines; Severity of Illness Index; Sildenafil Citrate; Sulfones; Surveys and Questionnaires; Tadalafil; Triazines; Vardenafil Dihydrochloride

The Real-Life Safety and Efficacy of vardenafil study is an international, open-label, prospective, noncomparative, noninterventional study in men with erectile dysfunction (ED).. To determine the safety and efficacy of vardenafil in a large international pool of men with ED (aged ≥ 18 years) and associated underlying conditions (N=73,946), in a real-life setting.. Patients attended an initial physician visit and one to two follow-up visits. Data were acquired by physician interviews and patient diaries and recorded in case report forms (CRFs). Data were pooled from 47 countries in Europe, Asia-Pacific, Latin America, and the rest of the world (excluding the United States and Japan for methodological reasons). Results were stratified by baseline ED severity, body mass index (BMI), and the presence of hypertension, diabetes, lipid metabolism disorder, or cardiovascular disease (CVD).. CRFs and patient questionnaires containing questions on overall improvement of erection, satisfaction with efficacy, and desire to continue vardenafil use.. Many participants had hypertension (32.0%), diabetes (22.1%), lipid metabolism disorder (14.6%), or CVD (42.2%). High percentages of patients reported improvements in erectile function, irrespective of baseline ED severity (mild, 97.0%; moderate, 96.2%; severe, 85.5%), BMI (<25, 94.1%; ≥ 25 and <30, 94.6%; ≥ 30, 92.9%), or the presence of hypertension (93.6%), diabetes (92.6%), lipid metabolism disorder (94.7%), or CVD (93.3%). Over 90% of patients, including those with underlying conditions, reported being "satisfied" or "very satisfied" with vardenafil efficacy, and stated their intention to continue vardenafil use after the end of the study period. The incidence of adverse events was low, and 97.0% of patients were either "satisfied" or "very satisfied" with vardenafil tolerability.. These data from a worldwide population of men with ED and associated underlying conditions show that vardenafil is effective and well-tolerated for the treatment of ED in a real-life setting, supporting its use as a first-line ED therapy.

Topics: Cardiovascular Diseases; Diabetes Mellitus; Erectile Dysfunction; Humans; Hypertension; Imidazoles; Lipid Metabolism Disorders; Male; Middle Aged; Patient Satisfaction; Phosphodiesterase 5 Inhibitors; Piperazines; Product Surveillance, Postmarketing; Prospective Studies; Severity of Illness Index; Sulfones; Triazines; Vardenafil Dihydrochloride

In recent years, the availability of effective oral pharmacological treatment for erectile dysfunction (ED) has revolutionized its management; however, it is still unclear how everyday clinical practice has changed in response to this evolving scenario.. The aim of this study is to describe general practitioners' (GPs) beliefs and attitudes toward the management of ED.. Each GP was asked to recruit consecutive men aged >or=18 years and sexually active, with already known erectile problems or with newly diagnosed ED.. A written questionnaire was used to investigate GPs' sociodemographic characteristics and their beliefs toward the management of ED.. Overall, 127 GPs (53.4%) returned the questionnaire and 124 enrolled patients for the study. Only 9.5% of the GPs reported routinely inquiring about ED of patients >40 years of age, whereas 45.7% did it only when the patient raised the problem. GPs' gender and age were associated with their beliefs about ED treatment and referral to specialist care. Overall, 932 patients were enrolled, of whom 38% had newly diagnosed ED. The problem came to light for initiative of patient in 80% of cases, and 84.8% of men were prescribed a treatment. Patients who on their own initiative discussed of their condition had an almost 3-fold increased probability to be treated than those whose GP began the discussion about ED (odds ratio [OR] = 2.6, confidence interval [CI] 95% 1.5-4.5). Patients followed by female physicians were significantly more likely to be referred to a specialist than those followed by male physicians (OR = 3.3, CI 95% 1.4-5.0).. The management of ED has become an integral component of clinical practice in primary care. Nevertheless, barriers in addressing sexual issues still persist. Appropriate training is needed for a proactive approach to ED screening and management in men over 40s.

Topics: Attitude of Health Personnel; Carbolines; Cardiovascular Diseases; Drug Prescriptions; Erectile Dysfunction; Humans; Imidazoles; Male; Middle Aged; Phosphodiesterase Inhibitors; Physician-Patient Relations; Piperazines; Practice Patterns, Physicians'; Primary Health Care; Purines; Sildenafil Citrate; Sulfones; Surveys and Questionnaires; Tadalafil; Triazines; Vardenafil Dihydrochloride