sildenafil-citrate and Cardiovascular-Diseases

PDE type 5 inhibitors (PDE5Is), such as sildenafil, tadalafil and vardenafil, are a class of drugs used to prolong the physiological effects of NO/cGMP signalling in tissues through the inhibition of cGMP degradation. Although these agents were originally developed for the treatment of hypertension and angina, unanticipated side effects led to advances in the treatment of erectile dysfunction and, later, pulmonary arterial hypertension. In the last decade, accumulating evidence suggests that PDE5Is may confer a wider range of clinical benefits than was previously recognised. This has led to a broader interest in the cardiovascular therapeutic potential of PDE5Is, in conditions such as hypertension, myocardial infarction, stroke, peripheral arterial disease, chronic kidney disease and diabetes mellitus. Here, we review the pharmacological properties and established licensed uses of this class of drug, along with emerging therapeutic developments and possible future indications.

Topics: Cardiovascular Diseases; Erectile Dysfunction; Humans; Hypertension; Male; Phosphodiesterase 5 Inhibitors; Sildenafil Citrate; Tadalafil

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

Phosphodiesterase (PDE) enzymes are widely distributed throughout the body, having numerous effects and functions. The PDE type 5 (PDE5) inhibitors are widely used to treat erectile dysfunction (ED). Recent, intense preclinical and clinical research with PDE5 inhibitors has shed light on new mechanisms and has revealed a number of pleiotropic effects on the cardiovascular (CV) system. To date, PDE5 inhibition has been shown to be effective for the treatment of idiopathic pulmonary arterial hypertension, and both sildenafil and tadalafil are approved for this indication. However, current or future PDE5 inhibitors have the potential of becoming clinically useful in a variety of CV conditions such as heart failure, coronary artery disease, and hypertension. The present review discusses recent findings regarding pharmacologic treatment of ED and its interaction with the CV system and highlights current and future clinical applications beyond ED.

Topics: Animals; Carbolines; Cardiovascular Diseases; Cardiovascular System; Erectile Dysfunction; Familial Primary Pulmonary Hypertension; Humans; Hypertension, Pulmonary; Male; Phosphodiesterase 5 Inhibitors; Phosphoric Diester Hydrolases; Piperazines; Purines; Sildenafil Citrate; Sulfones; Tadalafil

In view of the recent U.S. Food and Drug Administration's warning against the use of sildenafil in pediatric patients, we aimed to provide an updated overview of the dosing and safety of sildenafil in infants and to explore the relevance of the present safety concerns to the infant population.. The National Library of Medicine PubMed and Cochrane Database of Systematic Reviews were searched using the following terms: Sildenafil AND (infant OR infants OR newborn OR newborns OR child OR children OR childhood OR pediatric OR pediatrics OR paediatric OR paediatrics).. Studies presenting original clinical data regarding the dosing, use, or safety of sildenafil in infants with pulmonary hypertension would be included.. Of the 49 included studies, case reports and case series were the most common type of publications (n = 25). The identified trials included 625 children, with more than 140 infants. Persistent pulmonary hypertension of the newborn and pulmonary hypertension associated with other conditions were the most common underlying diagnoses.. There is currently no evidence of serious adverse event in infants exposed to sildenafil. Present safety concerns regarding the use of sildenafil in pediatric patients should be further explored before being applied to infant population. Sildenafil remains a valuable option for the treatment of pulmonary hypertension in young infants. Prospective studies should be designed in such a way that they include a safety assessment to evaluate potential adverse outcomes of sildenafil therapy in this population.

Topics: Blood Coagulation Disorders; Cardiovascular Diseases; Eye Diseases; Humans; Hypertension, Pulmonary; Infant; Infant, Newborn; Nervous System; Phosphodiesterase 5 Inhibitors; Piperazines; Purines; Sildenafil Citrate; Sulfones

Phosphodiesterase (PDE) enzymes are widely distributed throughout the body, having numerous effects and functions. The use of on demand PDE5 inhibitors (-Is) for the treatment of erectile dysfunction (ED) has recently obtained approval for chronic daily dosing for the same indication. There are published data supporting the use of PDE5-Is for the treatment of lower urinary tract symptoms (LUTS) caused by benign prostatic hyperplasia (BPH). Additional reports suggest benefit by these agents in patients with chronic heart failure, pulmonary hypertension, essential hypertension, and for the treatment of ischemia. Various central nervous system disorders have been described as targets by PDE5-Is. Sildenafil may have a potential therapeutic indication as a cognitive enhancer in age-related cerebral conditions. There is preclinical evidence for further investigation of the use of PDE5A -Is to improve recovery of cerebral function in humans after stroke by enhancing angiogenesis, neurogenesis and improving neurologic function. Sildenafil delays intestinal ulceration by an increase in the secretion of mucus/fluid and a decrease in hypermotility, and has a protective effect in reducing gastric damage. Larger scale, well designed clinical trials are needed to ascertain the safety, efficacy and cost-effectiveness of PDE5-Is in the future treatment of both urologic and non-urologic diseases. In this review, potential applications of PDE5-Is on urologic, cardiovascular, gastrointestinal, and central nervous system disorders will be updated.

Topics: Animals; Cardiovascular Diseases; Central Nervous System Diseases; Erectile Dysfunction; Female; Gastrointestinal Diseases; Humans; Male; Phosphodiesterase 5 Inhibitors; Piperazines; Purines; Sildenafil Citrate; Sulfones; Urologic Diseases

Phosphodiesterase type 5 (PDE5) inhibitors have proved to be efficacious, safe, and well tolerated, in clinical trials and practice, for men with erectile dysfunction (ED). However, many patients are not satisfied with treatment and discontinue it prematurely. This review discusses evidence-based strategies that nurse practitioners (NPs) can use to improve diagnosis of ED, optimize patient outcomes, and identify opportunities to detect other potentially serious comorbid conditions.. This article was based on a previously published review, which involved a PubMed-MEDLINE search of the clinical literature from January 1, 1998 (year of sildenafil's approval in many markets), through August 30, 2008 (date of search).. Strategies to optimize responses to PDE5 therapy are summarized by the mnemonic "EPOCH": Evaluating and educating to ensure realistic expectations of therapy; Prescribing a treatment individualized to the couple's needs and preferences; Optimizing drug dose/regimen and revisiting key educational messages at follow-up visits; Controlling comorbidities via lifestyle counseling, medications, and/or referrals; and Helping patients and their partners to seek other forms of therapy if they have decided not to use a PDE5 inhibitor.. The "EPOCH" mnemonic may remind NPs of steps to optimize treatment outcomes with PDE5 inhibitors.

Topics: Adult; Aged; Cardiovascular Diseases; Depression; Educational Status; Health Status; Humans; Impotence, Vasculogenic; Male; Middle Aged; Phosphodiesterase 5 Inhibitors; Piperazines; Prostatic Neoplasms; Purines; Risk Factors; Sexuality; Sildenafil Citrate; Sulfones; Treatment Outcome

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

To review special safety topics associated with sildenafil and to document the tolerability of 50- and 100-mg doses, overall and by age, in men with erectile dysfunction (ED).. Data were collated from 67 double-blind placebo-controlled (DBPC) trials (> 14,000 men) conducted by the manufacturer and from the manufacturer's postmarketing safety database (39,277 patients). The DBPC data were stratified by dose, starting dose and age (> or = 65 and > or = 75 years). Special safety topics included cardiovascular risk, priapism, non-arteritic anterior ischaemic optic neuropathy (NAION), impaired renal and hepatic function, drug interactions (i.e. nitrates, cytochrome P3A4 inhibitors, other ED therapies and alpha-blockers) and incorrect use.. Sildenafil was well tolerated at a dose of 50 or 100 mg in men with ED, overall, in those aged > or = 65 years, and in those aged > or = 75 years. Analyses of the databases did not reveal any causal link between sildenafil and cardiovascular events, or any new safety risks relating to cardiovascular events, priapism, NAION, hearing loss or drug interactions. In the small number of men with moderate impairment of renal function or hepatic function who were treated with sildenafil in DBPC trials, the safety profile was similar to that in men with no impairment of renal or hepatic function. Overdose with sildenafil was rare in the ED population. No new safety issues, emerging trends or adverse reactions were identified in conjunction with overdose, dependence, abuse or misuse.. This collated review confirms generally the good tolerability and established safety profile of sildenafil 50 and 100 mg in men with ED and reveals no new safety issues.

Topics: Aged; Cardiovascular Diseases; Dose-Response Relationship, Drug; Double-Blind Method; Drug Interactions; Drug Overdose; Erectile Dysfunction; Hearing Disorders; Humans; Kidney Diseases; Liver Diseases; Male; Middle Aged; Phosphodiesterase Inhibitors; Piperazines; Priapism; Product Surveillance, Postmarketing; Purines; Randomized Controlled Trials as Topic; Sildenafil Citrate; Sulfones; Treatment Outcome

Erectile dysfunction (ED) is a well-known entity with determined risk factors, which generally has a negative impact on quality of life. Obstructive sleep-disordered breathing (SDB), often referred to as obstructive sleep apnea, stands among the possible risk factors for ED.. Literature review suggests that SDB induces a spectrum of abnormalities in neural, hormonal, and vascular regulation that may contribute to the development of ED. While more studies are required to imply SDB as a risk factor for ED, several case series and expert opinion have contributed evidence for a causal relationship.. In clinical practice, men presenting with symptoms of sexual dysfunction often have concomitant sleep disorders requiring treatment. There is now evidence to suggest that treating SDB may be an effective treatment for ED. It is the authors' opinion that patients with erectile dysfunction would benefit from a sleep evaluation.

Topics: Aged; Cardiovascular Diseases; Continuous Positive Airway Pressure; Diabetes Mellitus, Type 2; Erectile Dysfunction; Humans; Hypertension; Kidney Failure, Chronic; Male; Middle Aged; Obesity; Phosphodiesterase Inhibitors; Piperazines; Prevalence; Pulmonary Disease, Chronic Obstructive; Purines; Quality of Life; Risk Factors; Sildenafil Citrate; Sleep Apnea, Obstructive; Sulfones

The therapy of systemic sclerosis (SSc) remains a challenge for dermatology, rheumatology, internal medicine, and other disciplines. Organ involvement, above all kidney and lungs, is a key therapeutic issue. The current developments in organ-specific therapy are the main topic of the article. Finally, possibilities of disease-modifying drugs and value of HSCT are discussed.

Topics: Angiotensin-Converting Enzyme Inhibitors; Cardiovascular Diseases; Fibrosis; Fingers; Gastrointestinal Agents; Hematopoietic Stem Cell Transplantation; Humans; Hypertension, Pulmonary; Iloprost; Kidney Transplantation; Piperazines; Purines; PUVA Therapy; Raynaud Disease; Recurrence; Scleroderma, Systemic; Sildenafil Citrate; Skin Ulcer; Sulfones; Ultraviolet Therapy; Vasodilator Agents

During many years, the symptom of erectile dysfunction was a matter for the urologist or the sexologist without efficacious treatment. Since 1999, the unexpected efficacy of sildenafil initially tested as a coronary vasodilatator emphasized the major role of an endothelial dysfunction potentially corrected by type 5 phosphodiesterase inhibitors (5-PDEI), which are able to reinforce the NO-dependant vasodilatation of cavernous arteries. Due to the medicalisation and the mediatisation of erectile dysfunction during the past five years, this symptom is now a matter for the cardiologist. The first reason was the query of cardiovascular safety of 5-PDEI. American and Britannic registries have established a good cardiovascular tolerability of these drugs including in patients with coronary heart disease according to the respect of contraindication in cases of coprescription with nitrates. The second was the association of erectile dysfunction with many cardiovascular risk factors concerned by the cardiologist. The third reason was the observation that erectile dysfunction could be a potential marker to identify patients with silent myocardial ischemia and relevant coronary artery disease. The Princeton consensus provides guidelines to help the cardiologist in the evaluation of patients with erectile dysfunction according to the cardiovascular risk level. Henceforth, erectile dysfunction should be considered by the cardiologist as "a sound of silence" of myocardial ischemia and should encourage to more aggressive evaluation and treatment of cardiovascular risk factors.

Topics: Cardiology; Cardiovascular Diseases; Erectile Dysfunction; Humans; Male; Phosphodiesterase Inhibitors; Physician's Role; Piperazines; Purines; Risk Factors; Sildenafil Citrate; Sulfones

Sildenafil citrate (Viagra; Pfizer Inc, New York, NY) relaxes vascular smooth muscle, resulting in modest reductions in blood pressure that are insufficient to stimulate a reflex increase in heart rate. These blood pressure reductions are similar for healthy men and men with coronary artery disease (CAD) or who use antihypertensive drugs. Sildenafil does not affect the force of cardiac contraction, and cardiac performance is unaffected. Sildenafil is mildly vasodilating in the coronary circulation and does not increase the risk of ventricular arrhythmia. During exercise and recovery, sildenafil does not cause clinically significant alterations in hemodynamic parameters in men with CAD, and it has no negative effects on coronary oxygen consumption, ischemia, or exercise capacity. Clinical trial data from >13,000 patients, 7 years of international postmarketing data, and observational studies of >28,000 men in the United Kingdom and 3813 men in the European Union reveal that (1) there are no special cardiovascular concerns when sildenafil is used in accordance with product labeling and (2) the risk for serious events such as myocardial infarction or death is not increased. However, because safety has not been established in patients with recent serious cardiovascular events, hypotension or uncontrolled hypertension, or retinitis pigmentosa, physicians should consult their current local prescribing information before prescribing sildenafil for these patients. Among men with erectile dysfunction treated with sildenafil, the adverse event profile is similar overall to that in men with comorbid cardiovascular disease (CVD), it is similar between those with and without CAD, and it is similar between those who take and those who do not take antihypertensive drugs (regardless of the number or class). In a controlled interaction study of sildenafil and amlodipine, the mean additional reduction in supine blood pressure was 8 mm Hg systolic and 7 mm Hg diastolic. Sildenafil should be used with caution in patients who take alpha-blockers because coadministration may lead to symptomatic hypotension in some individuals. When sildenafil is coadministered with an alpha-blocker, patients should be stable on alpha-blocker therapy before initiating sildenafil treatment and sildenafil should be initiated at the lowest dose. Also, in the absence of information specific to mixed alpha/beta blockers, such as carvedilol and labetalol, similar care should be taken as for alpha-blo

Topics: Cardiovascular Diseases; Cardiovascular Physiological Phenomena; Cardiovascular System; Erectile Dysfunction; Humans; Male; Phosphodiesterase Inhibitors; Piperazines; Purines; Sildenafil Citrate; Sulfones

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).. 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.. 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).. 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 < or = 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.. 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.

Topics: Adult; Aged; Aged, 80 and over; Cardiovascular Diseases; Coitus; Diabetes Complications; Dyslipidemias; Erectile Dysfunction; Humans; Hypertension; Logistic Models; Male; Middle Aged; Penile Erection; Phosphodiesterase Inhibitors; Piperazines; Purines; Randomized Controlled Trials as Topic; Retrospective Studies; Risk Factors; Sildenafil Citrate; Smoking; Sulfones; Surveys and Questionnaires; Treatment Outcome

Sildenafil is widely used to treat erectile dysfunction (ED). Because many patients with ED have cardiovascular diseases, doctors and patients are concerned over the safety of Sildenafil in patients with cardiovascular diseases. The review focuses on the safety of sildenafil for ED patients with cardiovascular diseases.

Topics: Cardiovascular Diseases; Erectile Dysfunction; Humans; Male; Piperazines; Purines; Sildenafil Citrate; Sulfones; Vasodilator Agents

Erectile dysfunction is common and closely associated with age and risk factors for cardiovascular disease. The oral selective inhibitors of phosphodiesterase type 5 (PDE5) have become the treatments of choice, owing to their convenience, general safety, and broad-spectrum effectiveness. For the same reasons, they have greatly simplified the workup. Thus, the general practitioner has gradually replaced the urologist for the initial management of erectile dysfunction and the proper evaluation of cardiac status before starting treatment with the PDE5 inhibitors. The following review provides a practical approach for the management of erectile dysfunction in primary care.

Topics: Cardiovascular Agents; Cardiovascular Diseases; Contraindications; Drug Interactions; Erectile Dysfunction; Humans; Interprofessional Relations; Male; Phosphodiesterase Inhibitors; Physicians, Family; Piperazines; Practice Patterns, Physicians'; Purines; Risk Factors; Sildenafil Citrate; Sulfones

More than 30 million men are estimated to have erectile dysfunction (ED) in the United States. Worldwide, ED is estimated to affect more than 150 million men, and that number is expected to exceed 300 million men by the year 2025. The prevalence of ED ranges from 7% in men aged 18-29 years to 85% in men aged 76-85 years. In addition, a recent report showed that 68% of patients with ED aged 18 years and older have at least one comorbid diagnosis of hypertension, hyperlipidaemia, diabetes or depression, and research suggests that ED may be an early indicator of systemic vascular disease. Viagra (sildenafil citrate), the first-in-class phosphodiesterase type 5 (PDE5) inhibitor, was introduced in 1998 for the treatment of ED. In the 7 years since its market launch, more than 750,000 physicians have prescribed sildenafil to more than 23 million men, helping establish an excellent safety and efficacy record. Clinical studies have demonstrated that sildenafil successfully treats ED of varied organic, psychogenic or mixed aetiology, and is effective in men with ED and comorbidities such as hypertension, hyperlipidaemia, diabetes or depression. Sildenafil was a breakthrough medication that addressed a previously unfulfilled medical need. The impact of sildenafil has stimulated academic, clinical and industrial research to better understand the nature of sexual function and develop better treatment and management for sexual dysfunctions such as ED. With the advent of other erectogenic therapies for the treatment of ED, this 7-year update will focus on the unique history and development of sildenafil, its current use and applications and its future directions and indications. Special emphasis is placed on the impact of sildenafil on our understanding of sexual health and on the extensive safety and efficacy data that have been amassed from numerous clinical trials.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Cardiovascular Diseases; Drug Interactions; Erectile Dysfunction; Female; Humans; Male; Piperazines; Purines; Sexual Dysfunction, Physiological; Sildenafil Citrate; Sulfones; Vasodilator Agents

Therapy of erectile dysfunction has been revolutionised in recent years, as specific pharmacological inhibitors of phosphodiesterase 5 (PDE5), such as sildenafil, tadalafil, or vardenafil, were shown to be highly effective in the treatment of erectile dysfunction. They dilate arterial smooth muscle cells of the corpora cavernosa, which express PDE5 abundantly, by inhibiting the breakdown of 3'5'-cyclic guanosine monophosphate. Despite theoretical concerns of a reduced myocardial tolerance to ischaemia or promoting cardiac arrhythmias, randomised trials and retrospective analyses do not support an increased cardiac risk with oral treatment. Therapeutic doses of PDE 5 inhibitors exhibit slight blood pressure lowering effects, and do not appear to compromise coronary blood flow in coronary artery disease. However, the combination of PDE5 inhibitors with any nitric oxide donor is absolutely contraindicated because of potentially life-threatening hypotension. Before prescribing medication for erectile dysfunction, any patient with cardiovascular disease should be evaluated for a potential risk of a cardiovascular event during sexual activity according to the Princeton Consensus Panel. When a stable cardiac condition can be achieved (low risk group), oral treatment for erectile dysfunction may be appropriate.

Topics: Administration, Oral; Apomorphine; Blood Pressure; Cardiovascular Diseases; Contraindications; Dopamine Agonists; Drug Interactions; Erectile Dysfunction; Humans; Hypotension; Male; Nitric Oxide Donors; Patient Selection; Phosphodiesterase Inhibitors; Piperazines; Purines; Risk Assessment; Sildenafil Citrate; Sulfones

Recent studies have highlighted the relation between erectile dysfunction (ED) and cardiovascular disease. In particular, the role of endothelial dysfunction and nitric oxide in ED and atherosclerotic disease has been elucidated. Given the large number of men receiving medical treatment for ED, concerns regarding the risk for sexual activity triggering acute cardiovascular events and potential risks of adverse or unanticipated drug interactions need to be addressed. A risk stratification algorithm was developed by the First Princeton Consensus Panel to evaluate the degree of cardiovascular risk associated with sexual activity for men with varying degrees of cardiovascular disease. Patients were assigned to 3 categories: low, intermediate (including those requiring further evaluation), and high risk. This consensus study from the Second Princeton Consensus Conference corroborates and clarifies the algorithm and emphasizes the importance of risk factor evaluation and management for all patients with ED. The panel reviewed recent safety and drug interaction data for 3 phosphodiesterase (PDE)-5 inhibitors (sildenafil, tadalafil, vardenafil), with emphasis on the safety of these agents in men with ED and concomitant cardiovascular disease. Increasing evidence supports the role of lifestyle intervention in ED, specifically weight loss and increased physical activity, particularly in patients with ED and concomitant cardiovascular disease. Special management recommendations for patients taking PDE-5 inhibitors who present at the emergency department and other emergency medical situations are described. Finally, further research on the role of PDE-5 inhibition in treating patients with other medical or cardiovascular disorders is recommended.

Topics: Age Distribution; Aged; Angina Pectoris; Cardiovascular Agents; Cardiovascular Diseases; Comorbidity; Coronary Disease; Drug Interactions; Erectile Dysfunction; Humans; Incidence; Male; Middle Aged; Piperazines; Prognosis; Purines; Risk Assessment; Severity of Illness Index; Sildenafil Citrate; Sulfones; Survival Rate

Sildenafil citrate is a drug commonly used to manage erectile dysfunction. It is designated chemically as 1-[[3-(6,7-dihydro-1-methyl-7-oxo-3-propyl-1H -pyrazolo[4,3-d]pyrimidin-5-yl)-4 ethoxyphenyl] sulfonyl]-4-methylpiperazine citrate (C22H30N6(O4)S). It is a highly selective inhibitor of cyclic guanine monophosphate-specific phosphodiesterase type 5. In late March through mid-November 1998, the US Food and Drug Administration (FDA) published a report on 130 confirmed deaths among men (mean age, 64 years) who received prescriptions for sildenafil citrate, a period during which >6 million outpatient prescriptions (representing about 50 million tablets) were dispensed. The US FDA recently reported that significant cardiovascular events, including sudden cardiac death, have occurred in men with erectile dysfunction who were taking sildenafil citrate. These reports have raised concerns that sildenafil citrate may increase the risk of cardiovascular events, particularly fatal arrhythmias, in patients with cardiovascular disease. In the past few years, the cardiac electrophysiological effects of sildenafil citrate have been investigated extensively in both animal and clinical studies. According to extensive data available to date, sildenafil citrate has been shown to pose minimal cardiovascular risks to healthy people taking this drug. Some precautions are needed for patients with cardiovascular diseases. However, the only absolute contraindication for sildenafil citrate is the concurrent use of nitrates. This article is intended to review sildenafil citrate's cardiovascular effects, as well as current debates about its arrhythmogenic effects.

Topics: Adult; Aged; Arrhythmias, Cardiac; Blood Pressure; Cardiovascular Diseases; Death, Sudden, Cardiac; Electrophysiology; Erectile Dysfunction; Heart Rate; Humans; Male; Middle Aged; Myocardial Contraction; Phosphodiesterase Inhibitors; Piperazines; Purines; Risk Factors; Sildenafil Citrate; Sulfones; Vasodilator Agents

The increased expression and activity of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex has emerged as a major common factor in the etiology of all forms of cardiovascular diseases since the upregulation of intravascular NADPH oxidase results in the formation of superoxide (O(2)(-)), which in turn promotes vasculopathy. An ever-increasing number of drugs commonly used in cardiovascular medicine have been shown to influence NADPH oxidase expression and activity. These include nitric oxide donors, nitroaspirin, eicosanoids, phosphodiesterase inhibitors, corticosteroids, antioxidants, and specific inhibitors. The objective of this review is to discuss these drugs in relation to the mechanisms underlying their effects on NADPH oxidase activity and the expression and therapeutic implications of these effects.

Topics: Cardiovascular Agents; Cardiovascular Diseases; Eicosanoids; Erectile Dysfunction; Glucocorticoids; Humans; Male; NADPH Oxidases; Phosphodiesterase Inhibitors; Piperazines; Purines; Sildenafil Citrate; Sulfones; Up-Regulation

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

Topics: Cardiovascular Diseases; Erectile Dysfunction; Humans; Male; Middle Aged; Piperazines; Purines; Sildenafil Citrate; Sulfones; Vasodilation; Vasodilator Agents

Erectile dysfunction (ED) is a common problem in men over 40-50 years of age. Risk factors include: diabetes, lipid abnormalities, smoking, hypertension, obesity, and lack of physical activity. Oral phosphodiesterase-5 inhibitors appear effective and safe in most cardiac patients.

Topics: Cardiovascular Diseases; Erectile Dysfunction; Humans; Male; Patient Education as Topic; Phosphodiesterase Inhibitors; Piperazines; Purines; Risk Factors; Sildenafil Citrate; Sulfones

The data in the literature on the relationship between sexual activity, with and without the use of sildenafil, and the occurrence of cardiovascular events (ventricular arrhythmias, nonfatal myocardial infarction, stroke and death) have been reviewed in patients with heart disease. To date, only patients with ischemic heart disease (IHD) have been investigated. The prevalence of premature ventricular beats during sexual intercourse is similar to that observed during other daily activities. Therefore, sexual activity does not seem to have a relevant arrhythmogenic effect. The incidence of sustained ventricular tachycardia during sexual intercourse in unknown. The relative risk of nonfatal myocardial infarction is 2.7 in males and 1.3 in females; however, the absolute risk appears extremely low and is similar in normal subjects and in patients with and without IHD. The risk appears to be restricted to the 2-hour time period after sexual intercourse. The incidence of stroke during sexual intercourse appears very low, but clear data are lacking. The incidence of death during sexual activity is unknown; the few available data suggest that it is very low. Extramarital sexual intercourse seems to increase the risk of death. The incidence of cardiovascular events after sildenafil administration has been investigated in placebo-controlled studies in patients with IHD. The incidence of nonfatal myocardial infarction, stroke and death did not significantly differ between sildenafil-treated and placebo-treated patients; therefore, sildenafil does not appear contraindicated in subjects with IHD. However, the drug should be administered with caution in patients with recent myocardial infarction or stroke, in those with active coronary ischemia and in patients with episodes of heart failure. The drug is absolutely contraindicated in patients using nitrates.

Topics: Cardiovascular Diseases; Erectile Dysfunction; Female; Heart Rate; Humans; Male; Phosphodiesterase Inhibitors; Piperazines; Purines; Risk Factors; Sexual Behavior; Sildenafil Citrate; Sulfones; Vasodilator Agents

The discovery in 1989 of sildenafil, a highly selective inhibitor of phosphodiesterase-5 (PDE-5), was the result of extensive research on chemical agents targeting PDE-5 that might potentially be useful in the treatment of coronary heart disease. Initial clinical studies on sildenafil in the early 1990s were not promising with respect to its antianginal potential. However, the incidental discovery of its antiimpotence effect led to its approval of for the treatment of erectile dysfunction. Thereafter, several reports of adverse cardiac events in patients on sildenafil raised concerns about its safety in cardiovascular disorders. Novel therapeutic indications are emerging for sildenafil with the recent discovery that PDE-5 is expressed in various other tissues such as the arterial vasculature, including pulmonary and coronary arteries, venous vasculature, skeletal muscles, platelets, and visceral and tracheobronchial muscles. In this review we briefly summarize the pharmacology of sildenafil and the current available evidence on its potential therapeutic applications in cardiovascular disorders.

Topics: 3',5'-Cyclic-GMP Phosphodiesterases; Aged; Blood Platelets; Cardiovascular Diseases; Child; Coronary Circulation; Cyclic Nucleotide Phosphodiesterases, Type 5; Endothelium, Vascular; Female; Hemodynamics; Humans; Hypertension, Pulmonary; Male; Middle Aged; Myocardial Contraction; Phosphodiesterase Inhibitors; Phosphoric Diester Hydrolases; Piperazines; Pulmonary Circulation; Purines; Sildenafil Citrate; Stress, Physiological; Sulfones; Sympathetic Nervous System; Vasodilator Agents

Erectile dysfunction (ED) and cardiovascular disease share many of the same risk factors and have some common elements of pathophysiology. Clinically, they often coexist. Another link between the two conditions is that sildenafil, the first oral therapeutic agent effective in treating ED, has been shown to potentiate the hypotensive effects of nitrates, a potentially serious side effect. Nitrates are commonly used in the treatment of coronary artery disease. As such, sildenafil (and, likely, other new phosphodiesterase type 5 [PDE5] inhibitors) is contraindicated in men who use nitrate medications. This article will examine the risk of an acute coronary event during sexual activity, and review an algorithm for evaluating the cardiac risk of a patient with ED. The interaction between PDE5 inhibitors and cardiac medications will be discussed, along with guidelines for using sildenafil in men with cardiac disease.

Topics: Administration, Oral; Aged; Cardiovascular Diseases; Comorbidity; Dose-Response Relationship, Drug; Erectile Dysfunction; Follow-Up Studies; Humans; Male; Middle Aged; Myocardial Infarction; Phosphodiesterase Inhibitors; Piperazines; Purines; Randomized Controlled Trials as Topic; Risk Assessment; Risk Factors; Sildenafil Citrate; Sulfones; Survival Rate

Initial reports of myocardial infarction and sudden death in men with erectile dysfunction who had taken sildenafil (sometimes in conjunction with nitrates) raised concerns that sildenafil may increase the risk of cardiovascular events in men with erectile dysfunction and vascular disease. A significant body of evidence now indicates that sildenafil generally has a good safety profile in men with erectile dysfunction and cardiovascular disease. Sildenafil therapy does not appear to be associated with ischaemic events either at the time of introduction of therapy or during longer-term use. Rates of discontinuation from sildenafil therapy due to adverse events are similar to placebo in men with cardiovascular disease. Sildenafil does not interact in a potentially hazardous way with antihypertensive or antianginal therapy, with the exception of nitrates. Nitrates should not be administered within 24 hours of sildenafil therapy, and care should be taken to determine whether sildenafil may have been used before nitrates are administered to patients. Sildenafil appears to be generally well tolerated in most patients with chronic, stable cardiovascular disease.

Topics: Antihypertensive Agents; Cardiovascular Diseases; Clinical Trials as Topic; Drug Interactions; Erectile Dysfunction; Hemodynamics; Humans; Male; Nitric Oxide Donors; Piperazines; Purines; Safety; Sildenafil Citrate; Sulfones; Vasodilator Agents

Topics: 3',5'-Cyclic-GMP Phosphodiesterases; Animals; Blood Pressure; Cardiovascular Diseases; Coronary Circulation; Cyclic Nucleotide Phosphodiesterases, Type 5; Humans; Isoenzymes; Organ Specificity; Phosphodiesterase Inhibitors; Phosphoric Diester Hydrolases; Piperazines; Pulmonary Circulation; Purines; Sildenafil Citrate; Sulfones; Vasospasm, Intracranial

We pooled data regarding myocardial infarction (MI) and cardiovascular death from more than 120 clinical trials of sildenafil citrate (Viagra) conducted from 1993 to 2001. During placebo-controlled trials, the rate of MI or cardiovascular death was 0.91 (95% CI: 0.52-1.48) per 100 person-years (PY) of follow-up among sildenafil-treated patients compared with 0.84 (95% CI: 0.39-1.60) per 100 PY of follow-up among placebo-treated patients. The relative risk of MI or cardiovascular death was 1.08 (95% CI: 0.45-2.77) for sildenafil compared with placebo (p = 0.88). During open-label studies, the rate of MI or cardiovascular death was 0.56 (95% CI: 0.44-0.72) per 100 PY of follow-up. This analysis showed that the rates of MI and cardiovascular death were low and comparable between men treated with sildenafil and those treated with placebo. The use of sildenafil was not associated with an increase in the risk of MI or cardiovascular death.

Topics: Adult; Aged; Aged, 80 and over; Cardiovascular Diseases; Clinical Trials as Topic; Humans; Impotence, Vasculogenic; Male; Middle Aged; Myocardial Infarction; Piperazines; Purines; Risk Factors; Sildenafil Citrate; Sulfones; Vasodilator Agents

Cardiologists are seeing increasing numbers of patients with erectile dysfunction (ED), which frequently coexists with cardiovascular disease. The pharmacologic profile of the new class of phosphodiesterase (PDE) inhibitors-specifically PDE5 inhibitors-and their potential effects on hemodynamic variables have therefore become significant factors in therapeutic decision making. Most of the published data linking PDE5 inhibitor effects and cardiovascular disease relate to sildenafil, although >or=2 new agents are in various stages of development and clinical trials. Sildenafil and other PDE5 inhibitors act on vascular smooth muscle, predominantly in the corpus cavernosum. PDE5 is not found in cardiomyocytes, and no effect of PDE5 inhibition on cardiac contractility has been demonstrated. On the basis of a safety database comprising thousands of men with ED, sildenafil has demonstrated minimal adverse effects in men with stable ischemia, hypertension, and/or severe coronary artery disease. Sildenafil has modest effects on hemodynamic variables and has been shown to increase coronary artery flow reserve. Alone or combined with >or=1 antihypertensive medication, sildenafil did not increase the incidence of adverse events or hypotensive episodes. Sildenafil-associated decreases in systolic and diastolic blood pressure, the result of its vasodilator activity, have been modest. Sildenafil has decreased both elevated pulmonary vascular resistance and elevated pulmonary artery pressures in patients with pulmonary vascular disease. Beneficial changes in hemodynamics have been observed with the use of sildenafil in patients with congestive heart failure with underlying ischemic and other dilated cardiomyopathies. No association between sildenafil and increased cardiovascular morbidity or mortality has emerged in analyses of clinical trial data.

Topics: 3',5'-Cyclic-GMP Phosphodiesterases; Blood Pressure; Cardiovascular Diseases; Drug Interactions; Erectile Dysfunction; Hemodynamics; Humans; Male; Muscle, Smooth, Vascular; Phosphodiesterase Inhibitors; Piperazines; Purines; Sildenafil Citrate; Sulfones

Topics: Antihypertensive Agents; Blood Pressure; Cardiovascular Diseases; Drug Interactions; Erectile Dysfunction; Humans; Male; Nitroglycerin; Piperazines; Purines; Risk Factors; Sildenafil Citrate; Sulfones; Vasodilator Agents

Sildenafil citrate is the first oral phosphodiesterase type 5 inhibitor approved for the treatment of erectile dysfunction. The wide use of sildenafil by patients with erectile dysfunction and cardiovascular disease has resulted in a considerable number of independent studies investigating the cardiovascular safety and functional role of the phosphodiesterase type 5-cyclic guanosine monophosphate-nitric oxide pathway in the cardiovascular system. Endothelial dysfunction, defined as a reduction in the bioavailability of nitric oxide, is associated with many of the common risk factors for cardiovascular disease and erectile dysfunction. Sildenafil has been demonstrated to improve the vasomotor aspect of endothelial dysfunction in patients with heart failure and diabetes. Hemodynamic studies suggest that sildenafil is a modest vasodilator with the potential to increase coronary blood flow and coronary flow reserve. In patients with ischemic heart disease, sildenafil is associated with reductions in mean arterial and pulmonary pressure with little effect on heart rate, cardiac output, and systemic or pulmonary vascular resistance. The absence of an effect on cardiac output supports the lack of an inotropic effect of sildenafil. This is consistent with the finding that sildenafil has no effect on cyclic adenosine monophosphate levels in the vasculature. Finally, exciting reports have emerged from clinical experience with the use of phosphodiesterase type 5 inhibitors in patients with pulmonary hypertension.

Topics: Cardiovascular Diseases; Heart; Hemodynamics; Humans; Piperazines; Purines; Sildenafil Citrate; Sulfones; Vasodilator Agents

A fatal case of sildenafil citrate (Viagra) overdosage is presented. The deceased was a 56-year old male found dead at home, with a past history of diabetes mellitus, hypertension, chronic alcoholism, anxio-depressive disorders, and erectile dysfunction. The main autopsy findings were cardiomegaly (650 g) with dilated cardiomyopathy, diffuse coronary atherosclerosis with no sign of acute ischaemic disease, and extensive fibrosis of the myocardium, especially affecting the cardiac conducting tissue. As measured by HPLC/MS, sildenafil concentration in postrmortem blood (6.27 microg/mL) exceeded at least four times the highest therapeutic levels previously reported. The results are discussed in the light of the literature about the cardiovascular side effects of sildenafil, with special emphasis on the recently evidenced arrhythmogenic potential of the drug. This is the first report of a fatality caused by sildenafil overdosage.

Topics: Alcoholism; Autopsy; Cardiovascular Diseases; Chromatography, High Pressure Liquid; Diabetes Complications; Drug Overdose; Fatal Outcome; Humans; Male; Mass Spectrometry; Middle Aged; Piperazines; Purines; Risk Factors; Sildenafil Citrate; Sulfones; Vasodilator Agents

Topics: Age Factors; Aging; Cardiovascular Diseases; Databases, Factual; Diabetes Complications; Endocrine System Diseases; Erectile Dysfunction; Humans; Internet; Male; Morbidity; Nervous System Diseases; Piperazines; Purines; Risk Factors; Sildenafil Citrate; Sulfones

Erectile dysfunction is a frequent condition in cardiovascular patients. Since the arrival of oral erection-supporting medication, patients want to know how safe sexual activity is in cardiovascular disease in general and during use of erection-supporting medication in particular. Sexual intercourse with a steady partner causes no more cardiovascular risk than normal daily activities such as ironing, 2 kilometers of walking without climbing, paperhanging, playing golf or gardening. The relative risk of myocardial infarction during sexual activity is not significantly higher than for healthy persons. The incidence of cardiovascular morbidity and mortality is not higher among users of sildenafil. Sildenafil is contraindicated in patients using long-acting nitrates or who may need to use short-acting nitrates, because the combination may cause a sharp fall of the blood pressure. No interactions have been observed with beta-receptor blockers, calcium antagonists, thiazide and loop diuretics and ACE inhibitors. Before prescribing a symptomatic (pharmaceutical) treatment for patients with an erection disorder, attention should be given tot the sexological, psychological and medical backgrounds of the disorder. Secondary prevention of atherosclerotic risk factors is also important: regulation of blood pressure and blood sugar level, hyperlipidaemia and obesity, as well as a change of lifestyle (giving up smoking, adapting of diet and more physical exertion). Patients with a very low cardiac capacity should be advised to refrain from treatment of the erection disorder.

Topics: Cardiovascular Diseases; Contraindications; Drug Interactions; Erectile Dysfunction; Humans; Isosorbide Dinitrate; Male; Netherlands; Nitric Oxide Donors; Nitroglycerin; Phosphodiesterase Inhibitors; Piperazines; Practice Guidelines as Topic; Purines; Sildenafil Citrate; Sulfones

Sildenafil has been registered for the treatment of erectile dysfunction since 1998. World wide a large number of patients were reported, dying of acute heart disease after using sildenafil. Therefore the patient instruction text was adapted. Simultaneous use of sildenafil and nitrates is contraindicated because of serious decrease of the blood pressure. The use of sildenafil can lead to physical stress in patients with a history of heart disease and a treadmill test assessment is advisable. In two years 38 adverse reactions were seen in 25 Dutch patients. The Dutch reports (three cardiovascular deaths since the introduction) also show the dilemmas in the assessment of the safety of sildenafil: is it the underlying disease or is it the drug that causes death? Further research into the adverse reactions has to be done, therefore reporting suspected side effects of sildenafil is important.

Topics: Adverse Drug Reaction Reporting Systems; Arrhythmias, Cardiac; Cardiovascular Diseases; Erectile Dysfunction; Humans; Male; Myocardial Infarction; Netherlands; Phosphodiesterase Inhibitors; Physical Exertion; Piperazines; Purines; Retinal Hemorrhage; Sildenafil Citrate; Sulfones

Erectile dysfunction (ED) affects as many as 30 million men in the United States. Its risk factors are similar to those for atherosclerotic heart disease. Physicians should ask male patients--particularly those with cardiovascular disease--about ED and men with confirmed ED about cardiovascular risk factors. Oral sildenafil is an effective therapy for both organic and psychogenic ED; it is contraindicated in patients taking organic nitrates.

Topics: Cardiovascular Diseases; Erectile Dysfunction; Humans; Male; Phosphodiesterase Inhibitors; Piperazines; Purines; Risk Factors; Sildenafil Citrate; Sulfones

Topics: Cardiovascular Diseases; Depressive Disorder; Diabetes Complications; Erectile Dysfunction; Humans; Hypertension; Male; Phosphodiesterase Inhibitors; Piperazines; Prostatic Diseases; Purines; Sildenafil Citrate; Smoking; Sulfones

There is now significant evidence that erectile dysfunction (ED) can be a symptom of cardiovascular disease, and can act as a marker for disease progression. National Health Service (NHS) prescribing restrictions on treatments for ED have recently been reviewed by the Department of Health, and current arrangements will not change. Unrestricted availability of licensed treatments for ED on the NHS, irrespective of the cause of the ED, may encourage men to present for investigation, enabling early detection of cardiovascular disease. Sildenafil citrate (Viagra), an effective treatment for ED, can also have a direct beneficial effect on cardiovascular disease. Unrestricted NHS availability of ED treatments such as sildenafil could facilitate greater achievement of National Service Framework targets for coronary heart disease.

Topics: Adult; Aged; Algorithms; Cardiovascular Diseases; Erectile Dysfunction; Humans; Male; Middle Aged; Patient Selection; Piperazines; Purines; Sildenafil Citrate; Sulfones; Vasodilator Agents

Cardiovascular risk factors are commonly associated with erectile dysfunction and should be identified and treated. Patients with cardiovascular diseases should be assessed and counselled regarding their fitness for sexual activity. The danger of concurrent use of sildenafil and nitrates under any circumstances, regardless of age and sex, must be highlighted at all levels of the community. Sildenafil is absolutely contraindicated in patients receiving treatment with long-acting nitrates for ischaemic heart disease. Patients who need sublingual short-acting nitrates infrequently should not be precluded from taking sildenafil, provided they are aware that sildenafil is not to be taken within 24 h of taking the nitrate.

Topics: 3',5'-Cyclic-GMP Phosphodiesterases; Algorithms; Cardiovascular Diseases; Coitus; Erectile Dysfunction; Humans; Male; Phosphodiesterase Inhibitors; Piperazines; Purines; Sildenafil Citrate; Sulfones

Diabetes can induce sexual disorders by different mechanisms. These troubles are more frequent in diabetics subjects. Thus, management of sexual impotence is an important aspect of diabetes care. However, most diabetologists are not trained to treat sexual disorders. The recent availability of oral drugs, i. e. Sildenafil (Viagra), has partly simplified the treatment of sexual impotence, particularly in diabetic patients. However, Viagra is efficient in only 60% cases in diabetic subjects. In the remaining cases, intracavernosal injections or vacuum can be used. Since Viagra has been available, more diabetic patients complained with sexual disorders, and ask for treatment of impotence. Cardio-vascular diseases must retain more attention in diabetic patients who are exposed to silencious myocardial ischemia. In such subjects, Viagra is not contra-indicated, but must be used after myocardial explorations, especially if the patients have cardio-vascular risk factors. However, patients and their doctors have been threatened by death cases reported with Viagra in United States. The lack of detailed informations has restrained Viagra's prescription. The following explains how to manage sexual disorders as part of diabetes care, and suggests rules for Viagra's prescription in diabetic patients.

Topics: Cardiovascular Diseases; Contraindications; Diabetes Complications; Diabetes Mellitus; Diabetic Angiopathies; Erectile Dysfunction; Humans; Male; Myocardial Ischemia; Phosphodiesterase Inhibitors; Piperazines; Purines; Sildenafil Citrate; Sulfones

Several drugs have been developed to treat patients with erectile dysfunction (ED). In general, patients prefer orally administered drugs. The use of these drugs (e.g. sildenafil and apomorphine) is reviewed. Because ED is a common problem in men with vascular disease it is important to assess the effect of these drugs on the cardiovascular system. The safe use of these drugs in patients with vascular disease needs to be clearly established in appropriately designed trials.

Topics: Arginine; Cardiovascular Diseases; Erectile Dysfunction; Humans; Male; Neurotransmitter Agents; Phosphodiesterase Inhibitors; Piperazines; Purines; Sildenafil Citrate; Sulfones

Erectile dysfunction (ED) is a common problem with a multifactorial aetiology. The treatment of ED has been revolutionised by the introduction of intracavernosal injections some two decades ago. However, the recent development of the orally-administered drug sildenafil (Viagra) has had a major impact on the treatment of ED. We discuss the trials with sildenafil with special reference to cardiovascular risk factors associated with ED.

Topics: Adult; Aged; Cardiovascular Diseases; Diabetes Complications; Erectile Dysfunction; Humans; Male; Middle Aged; Phosphodiesterase Inhibitors; Piperazines; Purines; Sildenafil Citrate; Smoking; Sulfones

Topics: Cardiovascular Diseases; Contraindications; Drug Interactions; Enzyme Inhibitors; Erectile Dysfunction; Humans; Male; Metabolic Clearance Rate; Piperazines; Purines; Risk; Sildenafil Citrate; Sulfones

Topics: Cardiovascular Diseases; Clinical Trials as Topic; Drug Interactions; Erectile Dysfunction; Humans; Male; Phosphodiesterase Inhibitors; Piperazines; Purines; Risk Assessment; Sildenafil Citrate; Sulfones; United Kingdom

Topics: Cardiovascular Diseases; Erectile Dysfunction; Humans; Male; Phosphodiesterase Inhibitors; Piperazines; Purines; Sildenafil Citrate; Sulfones

Topics: Cardiovascular Diseases; Erectile Dysfunction; Family Practice; Health Promotion; Humans; Male; Men; Phosphodiesterase Inhibitors; Piperazines; Prostatic Neoplasms; Purines; Sildenafil Citrate; Suicide; Sulfones; United States

The scavenger receptor CD36 influences the endothelial nitric oxide-cGMP pathway in vitro. Genetic variants that alter CD36 level are common in African Americans (AAs), a population at high risk of endothelial dysfunction.. To examine if the minor allele (G) of coding CD36 variant rs3211938 (G/T) which reduces CD36 level by approximately 50% influences endothelial function, insulin sensitivity (IS), and the response to treatment with the nitric oxide-cGMP potentiator sildenafil.. IS (frequently sampled iv glucose tolerance) and endothelial function (flow mediated dilation [FMD]) were determined in age- and body mass index-matched obese AA women with or without the G allele of rs3211938 (protocol 1). Effect of chronic sildenafil treatment on IS and FMD was tested in AA women with metabolic syndrome and with/without the CD36 variant, using a randomized, placebo-controlled trial (protocol 2).. Two-center study.. Obese AA women.. A total of 20-mg sildenafil citrate or placebo thrice daily for 4 weeks.. IS, FMD.. G allele carriers have lower FMD (P = .03) and cGMP levels (P = .01) than noncarriers. Sildenafil did not improve IS, mean difference 0.12 (95% confidence interval [CI], -0.33 to 0.58; P = .550). However, there was a significant interaction between FMD response to sildenafil and rs3211938 (P = .018). FMD tended to improve in G carriers, 2.9 (95% CI, -0.9 to 6.8; P = .126), whereas it deteriorated in noncarriers, -2.6 (95% CI, -5.1 to -0.1; P = .04).. The data document influence of a common genetic variant on susceptibility to endothelial dysfunction and its response to sildenafil treatment.

Topics: Adult; Cardiovascular Diseases; Case-Control Studies; CD36 Antigens; Drug Resistance; Endothelium, Vascular; Female; Genetic Predisposition to Disease; Humans; Insulin Resistance; Metabolic Syndrome; Middle Aged; Obesity; Phosphodiesterase 5 Inhibitors; Polymorphism, Single Nucleotide; Sildenafil Citrate; Treatment Outcome; Vasodilation

• To compare the underlying risk for diseases associated with erectile dysfunction (ED; i.e. cardiovascular disease and diabetes) in a population of men with mild ED relative to a general ED clinical trial population.. • Men enrolled in a randomized, double-blind placebo-controlled (DBPC) trial of sildenafil for the treatment of mild ED were compared with a database of men enrolled in 67 of the manufacturer's other DBPC sildenafil trials. • The main outcome measures were baseline demographics, comorbidities and concomitant medications.. • In both populations, most men were white, approximately one quarter were smokers, and most had an organic component to their ED etiology. • In the mild ED population (N = 176) versus the database population (N = 14,537), mean ± sd (range) age was 50 ± 12 (19-84) versus 55 ± 11 (18-89) years, body mass index was 29 ± 5 (20-48) versus 28 ± 5 (11-64) kg/m² and ED duration was 3.5 ± 3.2 (< 1-18) versus 4.6 ± 4.7 (< 1-45) years. • The prevalence of comorbidities associated with ED was similar (hypertension 26.1% (n = 46) vs 32.8%; diabetes mellitus 13.6% (n = 24) vs 22.1%; dyslipidemias 12.5% (n = 22) vs 11.7%; hypercholesterolemia 12.5% (n = 22) vs 9.5%; gastro-esophageal reflux disease 10.8% (n = 19) vs 6.0%; benign prostatic hyperplasia 9.7% (n = 17) vs 9.9%; depression 6.3% (n = 11) vs 5.6%; and anxiety 4.0% (n = 7) vs 1.6%), as was the rate of use of medications for those comorbidities.. • Men with mild ED have similar risk factors to a general ED clinical trial population. Thus, mild ED is an important indicator of risk for underlying disease associated with ED. • Inquiry into ED should be part of routine clinical evaluation to facilitate rapid identification and early intervention. • Men complaining of mild ED should be evaluated adequately for underlying cardiovascular risk.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Cardiovascular Diseases; Comorbidity; Diabetes Mellitus; Epidemiologic Methods; Erectile Dysfunction; Humans; Male; Middle Aged; Phosphodiesterase 5 Inhibitors; Piperazines; Purines; Sildenafil Citrate; Sulfones; Young Adult

Men with erectile dysfunction often have concurrent medical conditions. Conversely, men with these conditions may also have underlying erectile dysfunction. The prevalence of unrecognized erectile dysfunction in men with comorbidities commonly associated with erectile dysfunction was determined in men invited to participate in a double-blind, randomized, placebo-controlled trial of sildenafil citrate.. Men ≥30 years old presenting with ≥1 erectile dysfunction risk factor (controlled hypertension, hypercholesterolemia, smoking, metabolic syndrome, stable coronary artery disease, diabetes, depression, lower urinary tract symptoms, obesity [body mass index ≥30 kg/m2] or waist circumference ≥40 inches), and not previously diagnosed with erectile dysfunction were evaluated. The screening question, "Do you have erectile dysfunction?," with responses of "no," "yes," and "unsure," and the Erectile Function domain of the International Index of Erectile Function (IIEF-EF) were administered.. Of 1084 men screened, 1053 answered the screening question and also had IIEF-EF scores. IIEF-EF scores indicating erectile dysfunction occurred in 71% (744/1053), of whom 54% (399/744) had moderate or severe erectile dysfunction. Of 139 answering "yes," 526 answering "unsure," and 388 answering "no," 96%, 90%, and 36%, respectively, had some degree of erectile dysfunction. The mean±SD (range) number of risk factors was 2.9 ± 1.7 (3-8) in the "yes" group, 3.2 ± 1.7 (3-9) in the "unsure" group, and 2.6 ± 1.5 (2-8) in the "no" group.. Although awareness of having erectile dysfunction was low, most men with risk factors had IIEF-EF scores indicating erectile dysfunction. Erectile dysfunction should be suspected and assessed in men with risk factors, regardless of their apparent level of awareness of erectile dysfunction.. ClinicalTrials.gov Identifier NCT00343200.

Topics: Adult; Aged; Aged, 80 and over; Cardiovascular Diseases; Comorbidity; Diabetes Mellitus; Double-Blind Method; Erectile Dysfunction; Health Knowledge, Attitudes, Practice; Humans; Male; Middle Aged; Obesity; Phosphodiesterase 5 Inhibitors; Piperazines; Placebos; Purines; Risk Factors; Set, Psychology; Severity of Illness Index; Sildenafil Citrate; Sulfones; Surveys and Questionnaires; Treatment Outcome; Urologic Diseases

Assess the effectiveness of sildenafil in Asian males with erectile dysfunction (ED) and one or more of the co-morbidities, mild-to-moderate hypertension, dyslipidemia, and diabetes.. A six-week, double-blind, randomized, placebo-controlled, multicenter study was carried out in Thailand, Malaysia and Singapore. One hundred and fifty five male subjects were randomized (2:1) to sildenafil (n = 104) or placebo (n = 51). Sildenafil was started at 50 mg and increased (100 mg) or decreased (25 mg) at week 2 if necessary.. On the primary efficacy endpoint, sildenafil-treated subjects had significantly better scores on the International Index of Erectile Function (IIEF) questions 3 and 4 than placebo (p < 0.001, both questions). When accumulated into IIEF domains, all five domains were significant in favor of sildenafil. In addition, sildenafil-treated subjects were more satisfied with treatment and had a higher intercourse success rate. The majority of adverse events were mild in severity; the most commonly reported treatment-related events were dizziness (7.7%) and tinnitus (2.9%).. Sildenafil (25, 50, and 100 mg) was found to be an effective, safe, and well-tolerated treatment for ED in the present study population of Thai, Malaysian, and Singaporean males who also had increased cardiovascular risk

Topics: Asian People; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Dyslipidemias; Erectile Dysfunction; Humans; Hypertension; Malaysia; Male; Middle Aged; Phosphodiesterase Inhibitors; Piperazines; Purines; Risk Assessment; Risk Factors; Sildenafil Citrate; Singapore; Sulfones; Thailand; Treatment Outcome

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

Topics: Adult; Blood Pressure; Bronchi; Cardiovascular Diseases; Endothelium; Heart Ventricles; Humans; Male; Pilot Projects; Piperazines; Pulmonary Artery; Pulmonary Disease, Chronic Obstructive; Purines; Sildenafil Citrate; Sulfones; Treatment Outcome; Ultrasonography; Vasodilator Agents

Patients with cardiovascular diseases frequently complain of erectile dysfunction especially when treated with beta-blockers. In order to assess whether the effect of beta-blockers on erectile dysfunction is in part related to patient knowledge of the drug side effects, 96 patients (all males, age 52+/-7 years) with newly diagnosed cardiovascular disease and not suffering from erectile dysfunction entered a two phase, single cross over study.. During the first phase of the study patients received atenolol 50mg o.d. (A), 32 patients were blinded on the drug given (group A), 32 were informed on the drug given but not on its side effects (group B) and 32 took A after being informed on its side effects on erectile function (group C). After 3 months the incidence of erectile dysfunction was 3.1% in the group A, 15.6% in group B and 31.2% in group C (P<0.01). All patients reporting ED entered the second phase of the study and were randomised to receive Sildenafil 50mg and placebo in a cross over study. Sildenafil citrate and placebo were equally effective in reversing erectile dysfunction in all but one patient reporting ED with Atenolol.. Our results show that the knowledge and prejudice about side effects of beta-blockers can produce anxiety, that may cause erectile function.

Topics: Adrenergic beta-Antagonists; Angina Pectoris; Anxiety; Attitude to Health; Awareness; Cardiovascular Diseases; Cross-Over Studies; Humans; Hypertension; Impotence, Vasculogenic; Male; Middle Aged; Phosphodiesterase Inhibitors; Piperazines; Placebos; Purines; Sildenafil Citrate; Sulfones

Men with cardiovascular disease (CVD) are more likely to have erectile dysfunction (ED) than the general population, as both conditions share risk factors and some drugs used to treat CVD may induce ED as a side-effect. This study was undertaken to assess the efficacy and safety of sildenafil citrate for the treatment of ED in men with CVD who were receiving treatment with beta-blockers and/or angiotensin-converting enzyme inhibitors and/or calcium-channel blockers, but not nitrates. Treatment with sildenafil was associated with significant increases in the mean end-of-treatment scores for the questions from the International Index of Erectile Function that assess the ability to achieve and maintain erections (p = 0.0001). Furthermore, 71% of patients taking sildenafil reported improved erections compared with 24% taking placebo (p = 0.0001). This study also showed that sildenafil was well tolerated in patients with CVD and ED. Besides flushing, no treatment-related cardiovascular adverse events were noted for sildenafil.

Topics: Adrenergic beta-Antagonists; Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Calcium Channel Blockers; Cardiovascular Diseases; Double-Blind Method; Humans; Impotence, Vasculogenic; Male; Middle Aged; Phosphodiesterase Inhibitors; Piperazines; Prospective Studies; Purines; Sildenafil Citrate; Sulfones; Treatment Outcome

Sildenafil is a selective and by oral administration potent type-5 phosphodiesterase (PDE 5) inhibitor, which increases the erection by corpus cavernosum smooth muscle relaxation. In a non-placebo controlled study, 134 patients with erectile dysfunction were treated with oral sildenafil. The aim of the study was to estimate the efficacy and adverse effects of this treatment. 51 patients (38%) had psychogenic, and 83 (62%) organic origin of the erectile dysfunction. 73 of them have already had some treatment for this problem before. The effective dose was 50 mg for 84 patients (63%), 100 mg for 32 (24%) and 25 mg for 4 patients. The treatment was effective for 120 patients (90%). The most common adverse effect was flushing in 18 (13%) and headache in 9 (7%) cases, two patients had headache and flushing together. Nasal congestion and visual disturbances were complained by two patients. Two patients reported prolonged (max. 2h) erections. Cardiological investigation was performed for cardiovascular patients and for patients with risk factors. Exact criteria of the cardiological opinion of sildenafil treatment are reviewed. Cardial or other serious adverse effects were not observed. It was not necessary to stop the treatment because of the adverse effects. The authors found, that sildenafil is an effective and safe treatment for the erectile dysfunction.

Topics: Adult; Aged; Cardiovascular Diseases; Erectile Dysfunction; Humans; Male; Middle Aged; Phosphodiesterase Inhibitors; Piperazines; Purines; Risk Factors; Sildenafil Citrate; Sulfones; Treatment Outcome

Sildenafil citrate has been shown to be effective in a wide range of patients with erectile dysfunction and has been approved in the United States for this indication. The overall clinical safety of oral sildenafil, a potent inhibitor of phosphodiesterase type 5, in the treatment of erectile dysfunction was evaluated in more than 3700 patients (with a total of 1631 years of exposure worldwide). Safety and tolerability data were analysed from a series of double-blind, placebo-controlled studies and from 10 open-label extension studies of sildenafil in the treatment of erectile dysfunction. A total of 4274 patients (2722 sildenafil, 1552 placebo; age range 19-87 y) received double-blind treatment over a period of up to six months' duration, and 2199 received long-term, open-label sildenafil for up to 1 y. The most commonly reported adverse events (all causes) were headache (16% sildenafil, 4% placebo), flushing (10% sildenafil, 1% placebo), and dyspepsia (7% sildenafil, 2% placebo) and they were predominantly transient and mild or moderate in nature. These adverse events reflect the pharmacology of sildenafil as a phosphodiesterase type 5 inhibitor. No cases of priapism were reported. The rate of discontinuation due to adverse events (all causes) was comparable for patients treated with sildenafil (2.5%) and placebo (2.3%). In open-label extension studies, 90% of patients completed long-term sildenafil treatment, with only 2% withdrawing due to adverse events. Sildenafil is a well-tolerated oral treatment for erectile dysfunction.

Topics: 3',5'-Cyclic-GMP Phosphodiesterases; Adolescent; Adult; Aged; Aged, 80 and over; Cardiovascular Diseases; Double-Blind Method; Dyspepsia; Enzyme Inhibitors; Erectile Dysfunction; Flushing; Headache; Humans; Middle Aged; Piperazines; Placebos; Purines; Sildenafil Citrate; Sulfones

Topics: Animals; Aphrodisiacs; Cardiovascular Diseases; Honey; Humans; Panthera; Sildenafil Citrate

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

Much evidence indicates that metabolic syndrome is strongly correlated with a decrease in nitric oxide and an increase in oxidative stress leading to cardiovascular alterations. In recent years, gut microbiota has emerged as a new contributor to the metabolic syndrome establishment and associated cardiovascular diseases, but the underlying mechanisms remain unclear. We hypothesized that a positive modulation of cyclic guanosine monophosphate (cGMP) pathway, through phosphodiesterase type 5 (PDE5) inhibition could prevent cardiovascular alterations and gut dysbiosis that may be associated to metabolic syndrome. Spontaneously hypertensive rats (SHR) were randomly divided into 4 groups: control, cafeteria diet (CD) and sildenafil citrate treated groups (5mg/kg per os) were given either a CD or a standard chow diet for 10 weeks. Body weight, arterial blood pressure and glucose tolerance test were monitored. At the 10th week, cardiac inotropy and coronary perfusion pressure were evaluated on isolated heart according to Langendorff method. Cumulative concentration response curves to phenylephrine and acetylcholine were determined on thoracic aorta rings for vascular reactivity evaluation. Faecal samples were collected for the gut microbiota analysis. Compared to the control group, CD-fed rats showed a significant increase in body weight gain, arterial blood pressure and were glucose intolerant. This group showed also a decrease in β-adrenoceptor-induced cardiac inotropy and coronary vasodilation. Gut microbiota analysis revealed a significant reduction in the abundance of Lactobocillus spp in cafeteria diet-fed rats when compared to the control ones. Sildenafil citrate long-term treatment decreased weight gain and arterial blood pressure, improved coronary vasodilation and reduced α1-adrenoceptor-induced vasoconstriction in CD group. However, it did not reverse gut dysbiosis induced by chronic CD feeding. These results suggest that cGMP pathway targeting may be a potential therapeutic strategy for the management of the metabolic syndrome and associated cardiovascular disorders.

Topics: Acetylcholine; Animals; Aorta, Thoracic; Blood Pressure; Cardiovascular Diseases; Cyclic GMP; Diet; Disease Models, Animal; Gastrointestinal Microbiome; Glucose Tolerance Test; Male; Metabolic Syndrome; Phenylephrine; Phosphodiesterase 5 Inhibitors; Rats; Rats, Inbred SHR; Sildenafil Citrate; Vasodilation; Vasodilator Agents

To evaluate treatment response in men with erectile dysfunction (ED) and concomitant comorbidities.. Data were pooled from 42 placebo-controlled, flexible-dose sildenafil trials. In most trials, the sildenafil dose was 50 mg, taken ~1 hour before sexual activity but not more than once daily, with adjustment to 100 or 25 mg as needed. The overall population (N=9413) was stratified by age (<45, 46-64, ≥65 years). Treatment response was defined as a minimal clinically important difference (MCID) from baseline in the International Index of Erectile Function-Erectile Function (IIEF-EF) domain score of >2, >5 and >7 for men with mild, moderate and severe ED at baseline, respectively, or an IIEF-EF domain score ≥26 (no ED) at end-point.. In the overall population, treatment response using the IIEF-EF MCID definition was significantly greater (P<.0001) with sildenafil vs placebo in men with no comorbidity (77% vs 33%), cardiovascular disease/hypertension only (71% vs 27%), diabetes only (63% vs 24%) or depression only (78% vs 29%). Using an IIEF-EF score ≥26, treatment response was significantly greater (P<.0001) with sildenafil vs placebo in men with no comorbidity (49% vs 17%), cardiovascular disease/hypertension only (48% vs 12%), diabetes only (40% vs 12%) or depression only (60% vs 17%). With each definition, the treatment response for each age and comorbidity was significantly greater (P≤.0065) with sildenafil vs placebo.. The treatment response was significantly greater with sildenafil vs placebo in men with ED and each comorbidity regardless of age.

Topics: Aged; Cardiovascular Diseases; Depression; Diabetes Mellitus, Type 2; Erectile Dysfunction; Health Status; Humans; Hypertension; Male; Middle Aged; Remission Induction; Risk Factors; Severity of Illness Index; Sildenafil Citrate; Vasodilator Agents

Diabetes and cardiovascular disease are risk factors for erectile dysfunction (ED). Selective inhibitors of the type 5 phosphodiesterase are the first option for treating ED. However, it is unknown why there are patients with low response to this treatment. Polymorphisms in the PDE5A gene may influence the response to PDE5 inhibitors treatment.. The aim of this study is to analyze the relationship between PDE5A polymorphisms, diabetes, and the efficacy of sildenafil treatment.. A Spanish prospective cohort of 170 Caucasian male patients diagnosed with ED and ischemic heart disease treated with angioplasty was studied.. ED was evaluated according to the 5-item version of the International Index for Erectile Function before and after treatment with sildenafil 50 mg. The gene sequence of the PDE5A gene was analyzed for the presence of rs12646525 and rs3806808 polymorphisms. Glucose and glycosylated hemoglobin levels were measured in blood serum samples. The relationship between treatment response, genotype, and glycemic status was analyzed.. Patients with G-allele of rs3806808 polymorphism showed a worse response to the treatment compared to TT-homozygote patients. Nondiabetic G-allele carriers showed a worse treatment response than TT-homozygotes patients. These differences were not seen in diabetic patients. There were no significant differences in treatment response according to the rs12646525 polymorphism in total population or according to the glycemic status. Logistic regression analysis showed that nondiabetic carriers of the major allele of both the rs12646525 and rs3806808 polymorphism had a significantly higher likelihood to respond to the treatment than diabetic patients carriers of the minor allele (P < .05).. The response to sildenafil treatment depends on polymorphisms in the PDE5A gene and the glycemic status of the patients.

Topics: Aged; Cardiovascular Diseases; Cyclic Nucleotide Phosphodiesterases, Type 5; Erectile Dysfunction; Humans; Male; Middle Aged; Penile Erection; Phosphodiesterase 5 Inhibitors; Piperazines; Polymorphism, Genetic; Prospective Studies; Risk Factors; Sildenafil Citrate; Treatment Outcome

Proteasome functional insufficiency is implicated in a large subset of cardiovascular diseases and may play an important role in their pathogenesis. The regulation of proteasome function is poorly understood, hindering the development of effective strategies to improve proteasome function.. Protein kinase G (PKG) was manipulated genetically and pharmacologically in cultured cardiomyocytes. Activation of PKG increased proteasome peptidase activities, facilitated proteasome-mediated degradation of surrogate (enhanced green fluorescence protein modified by carboxyl fusion of degron CL1) and bona fide (CryAB(R120G)) misfolded proteins, and attenuated CryAB(R120G) overexpression-induced accumulation of ubiquitinated proteins and cellular injury. PKG inhibition elicited the opposite responses. Differences in the abundance of the key 26S proteasome subunits Rpt6 and β5 between the PKG-manipulated and control groups were not statistically significant, but the isoelectric points were shifted by PKG activation. In transgenic mice expressing a surrogate substrate (GFPdgn), PKG activation by sildenafil increased myocardial proteasome activities and significantly decreased myocardial GFPdgn protein levels. Sildenafil treatment significantly increased myocardial PKG activity and significantly reduced myocardial accumulation of CryAB(R120G), ubiquitin conjugates, and aberrant protein aggregates in mice with CryAB(R120G)-based desmin-related cardiomyopathy. No discernible effect on bona fide native substrates of the ubiquitin-proteasome system was observed from PKG manipulation in vitro or in vivo.. PKG positively regulates proteasome activities and proteasome-mediated degradation of misfolded proteins, likely through posttranslational modifications to proteasome subunits. This may be a new mechanism underlying the benefit of PKG stimulation in treating cardiac diseases. Stimulation of PKG by measures such as sildenafil administration is potentially a new therapeutic strategy to treat cardiac proteinopathies.

Topics: Adenoviridae; Animals; Cardiovascular Diseases; Cells, Cultured; Cyclic GMP-Dependent Protein Kinase Type I; Cyclic GMP-Dependent Protein Kinases; Desmin; Enzyme Activation; Green Fluorescent Proteins; Humans; Male; Mice; Mice, Transgenic; Myocytes, Cardiac; Phosphodiesterase 5 Inhibitors; Piperazines; Proteasome Endopeptidase Complex; Protein Processing, Post-Translational; Proteostasis Deficiencies; Purines; Rats; RNA, Small Interfering; Sildenafil Citrate; Sulfones

The low pharmacological response to phosphodiesterase type 5 inhibitors represents an expression of higher endothelial damage in certain categories of patients with erectile dysfunction and high cardiovascular risk. The present study evaluated this objective in type 2 diabetic patients with erectile dysfunction, classified as "non responders" to Sildenafil.. Eighteen "responder" and twelve "non responder" type 2 diabetic patients were evaluated, relatively to different levels of endothelial damage, through the diagnostic use of a new immunophenotype of circulating endothelial progenitor cells (CD45neg/CD34pos/CD144pos) and endothelial microparticles (CD45neg/CD144pos/Annexin Vpos), recently developed and published by our group.. "Non responder" patients showed a significant higher severity [8.0±3.0 (International Index of Erectile Function-abbreviated version with 5 questions) vs 14.0±3.0] and duration (10.0±2.0 vs 7.0±2.0 years) of erectile dysfunction, higher level of penile arterial insufficiency (peak systolic velocity=13.0±16.0 vs 28.0±26.0cm/s; acceleration time=153±148 vs 125±128 mm/s) and finally a significant higher level of endothelial apoptosis [0.15±0.13 vs 0.05±.0.03% (serum concentrations of endothelial microparticles)] associated with higher serum concentrations of circulating late immunophenotype of endothelial progenitor cells (0.40±0.35 vs 0.12±.0.10%).. The results of this study corroborate the clinical value of the low clinical response to phosphodiesterase type 5 inhibitors in the treatment of erectile dysfunction in the patients with high cardiovascular risk profile, such as diabetics. In addition, the markers used in this study confirm their potential application in clinical practice as useful indicators of endothelial alteration. However, in the future we will have to assess a larger number of patients and for a longer period of observation in order to better understand the causal and temporal relations.

Topics: Aged; Apoptosis; Arteries; Cardiovascular Diseases; Cell-Derived Microparticles; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Drug Resistance; Endothelium, Vascular; Flow Cytometry; Humans; Impotence, Vasculogenic; Italy; Male; Middle Aged; Penis; Phosphodiesterase 5 Inhibitors; Piperazines; Purines; Risk Factors; Severity of Illness Index; Sildenafil Citrate; Sulfones; Treatment Outcome

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

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

To evaluate whether the response to sildenafil administration in patients with arterial erectile dysfunction (ED) was related to their peak systolic velocity (PSV), peripheral atherosclerosis, cardiovascular risk factors (RF) and/or comorbidities at low cardiovascular risk.. We enrolled 97 patients with 1-2 RF and comorbidities, combined with arterial ED alone (group A, n = 27), ED plus atherosclerotic carotid artery (group B, n = 23), ED plus lower limb artery abnormalities (group C, n = 25), and ED plus carotid and lower limb artery abnormalities (group D, n = 22). Sildenafil efficacy (100 mg twice a week for 12 weeks) was also examined in patients with =or>3 RF, peripheral atherosclerosis and no cardiovascular comorbidities (group E, n = 20).. Median PSV was 24.1, 21.0, 19.3, 14.5 and 17.5 cm/s in groups A, B, C, D and E, respectively. Sildenafil response was higher in group A patients (77.8%), intermediate in groups B and C (65.2% and 56%) and lowest in groups D (45.4%) and E (50%), and the response in latter two groups was significantly lower than in the other three groups. In addition, sildenafil response was negatively influenced by: =or>3 RF, peripheral atherosclerosis and no systemic comorbidity, or presence of 1-2 RF associated with extended atherosclerosis and comorbidities. The number of comorbidities was positively related to atherosclerosis localization or extension (25, 35, 38 and 47 in groups A, B, C and D, respectively).. Low sildenafil efficacy in patients with arterial ED was associated with extended atherosclerosis. These patients should undergo extensive ultrasonography and a full cardiovascular examination.

Topics: Aged; Arterial Occlusive Diseases; Atherosclerosis; Cardiovascular Diseases; Erectile Dysfunction; Humans; Lower Extremity; Male; Middle Aged; Physical Examination; Piperazines; Purines; Regional Blood Flow; Retrospective Studies; Risk Factors; Sildenafil Citrate; Sulfones; Treatment Outcome; Vasodilator Agents

To assess the incidence of serious cardiovascular disease (CVD) events [i.e. myocardial infarction (MI) and stroke] and all-cause mortality in men with erectile dysfunction (ED) who received prescriptions for sildenafil.. The International Men's Health Study (IMHS) was a prospective, observational cohort study of patients with ED and a new or existing prescription for sildenafil. Baseline and follow-up questionnaires provided information on demographics, CVD risk factors and ED. Postevent questionnaires were mailed to patients following possible nonfatal CVD events to collect information related to exposure to sildenafil/ED treatments before the event.. Thirty-five CVD events were reported in 30 patients in the analysis set (n = 3813). The incidence of all-cause mortality, MI and stroke was 0.4, 0.6 and 0.1 per 100 patient-years of observation respectively. Among the six men who reported using sildenafil in the month before a nonfatal CVD event, two reported use in the 24 h before the event.. The results of the IMHS support previous reports that ED and CVD are often comorbid and share risk factors.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Cardiovascular Diseases; Cohort Studies; Erectile Dysfunction; Humans; Male; Men's Health; Middle Aged; Phosphodiesterase Inhibitors; Piperazines; Prospective Studies; Purines; Risk Factors; Sildenafil Citrate; Sulfones

Erectile dysfunction is related to penile arterial endothelial nitric oxide production. Asymmetric dimethylarginine (ADMA) and E-selectin are often considered plasma markers of endothelial function.. This study investigated the relationship between these plasma markers and cardiovascular risk factors in patients with erectile dysfunction.. Cardiovascular risk factors, ADMA and E-selectin were assessed in 45 patients with erectile dysfunction. Plasma markers showed associations with baseline risk factors. E-selectin levels showed an inverse relationship with age (p = 0.005) and statin therapy (p = 0.03) and a weak association with concomitant beta-blocker therapy (p = 0.05). Compared to these relatively weak associations with cardiovascular risk factors, ADMA levels showed strong associations with pulse pressure (p < 0.001), lack of smoking (p = 0.002) and lipoprotein (a) (p = 0.004) concentrations and weak associations with LDL-cholesterol (p = 0.02), and C-reactive protein levels (p = 0.04). ADMA levels correlated with E-selectin (partial r = 0.76; p < 0.001) after adjustment for lipoprotein (a), pulse pressure and smoking. No change in E-selectin or ADMA levels was seen after 70 days therapy with sildenafil and no relationship was found between either plasma marker and the acute pulse wave response to a single challenge dose of sildenafil.. ADMA levels correlate at baseline with some cardiovascular risk factors including inflammatory markers and lipoprotein (a) in patients with erectile dysfunction.

Topics: 3',5'-Cyclic-GMP Phosphodiesterases; Arginine; Blood Pressure; C-Reactive Protein; Cardiovascular Diseases; Cholesterol, LDL; E-Selectin; Enzyme Inhibitors; Erectile Dysfunction; Humans; Male; Middle Aged; Nitric Oxide Synthase; Piperazines; Purines; Risk Factors; Sildenafil Citrate; Sulfones

The introduction of sildenafil put the risk of cardiovascular disease (CVD) among men with erectile dysfunction (ED) on the agenda of physicians. The question arose, Is EDsentinel to CVD? We sought to answer this question in the present study.. A historical cohort study was set up using medical records of general practices all over the Netherlands. Incident cases of ED were selected before and after the introduction of sildenafil using a catchment population of 60,000 men aged 35 to 74 years. Two to three men without ED (controls) were, subsequently, matched to each case. Incidence of CVD was determined for cases and controls, respectively.. Overall, incidence of ED doubled from 5.3 per 1000 men-years in the period before introduction of sildenafil to 10.1 after the introduction. The relative risk of incident CVD among men with ED compared to controls was 1.7 [95%-CI 0.9-3.3] before the introduction and 1.1 [95%-CI 0.6-1.8] afterwards.. While ED could be seen as a marker for CVD before the introduction of sildenafil, it was clearly not afterwards.

Topics: Adult; Age Factors; Aged; Cardiovascular Diseases; Case-Control Studies; Cohort Studies; Erectile Dysfunction; Humans; Incidence; Male; Middle Aged; Myocardial Infarction; Piperazines; Prevalence; Proportional Hazards Models; Purines; Retrospective Studies; Risk Factors; Sexual Behavior; Sildenafil Citrate; Sulfones; Vasodilator Agents

Erectile dysfunction is related to endothelial function. Cardiovascular risk factors determine endothelial function. Sildenafil is effective in treatment of erectile dysfunction but shows variable results. This study investigated the relationship of cardiovascular risk factors to acute and chronic responses to sildenafil.. Cardiovascular risk factors and acute and chronic pulse wave responses to a single 50-mg dose of sildenafil were assessed in 45 patients with erectile dysfunction confirmed by low international index of erectile function (IIEF) score before and after chronic therapy with sildenafil.. On recruitment all patients showed evidence of erectile dysfunction with an IIEF score of 5 points (1 to 20 points). Chronic sildenafil therapy resulted in an increase of IIEF score of 13 points (range -1 to +24 points) and 24 patients (53%) achieved an IIEF score>or=21 points. Improvement in erectile function in response to sildenafil (rn=0.79; P<.001) was dependent on initial erectile function (P=.002) and baseline apolipoprotein B (P=.01). Vascular responses to acute treatment with sildenafil were assessed using pulse wave analysis. Acute changes in stiffness index induced by sildenafil (rn=0.65; P<.001) were related to apolipoprotein A-1 (P=.006), B (P=.02), and lipoprotein(a) (P=.008) concentrations, whereas reflection index (rn=0.69; P<.001) was related to pulse pressure (P<.001), albumin-to-creatinine ratio (P=.007), and lipoprotein(a) (P=.02).. The extent of acute and chronic effects of sildenafil on erectile function and pulse wave profiles is determined by metabolic cardiovascular risk factors. Improved cardiovascular risk factor control is likely to increase the efficacy of phosphodiesterase-5 inhibitor therapy in the treatment of erectile dysfunction.

Topics: Aged; Apolipoprotein A-I; Apolipoproteins B; Biomarkers; Blood Pressure; Cardiovascular Diseases; Case-Control Studies; Endothelium, Vascular; Erectile Dysfunction; Heart Rate; Humans; Lipoprotein(a); Male; Middle Aged; Phosphodiesterase Inhibitors; Piperazines; Purines; Risk Assessment; Risk Factors; Severity of Illness Index; Sildenafil Citrate; Sulfones; Time Factors; Treatment Outcome; Vasodilator Agents

Erectile dysfunction (ED) affects approximately 30 million men in the United States. The objectives of this study were to (1) assess the cost and utilization of sildenafil citrate (Viagra), an oral therapeutic agent for ED, in a large managed care organization (MCO) with a quantity limit of 6 units per 30-day supply and (2) describe the incidence of comorbid conditions and the severity of cardiovascular disease in adult male users of sildenafil.. Pharmacy claims for sildenafil were identified from an administrative database of claims with dates of service in calendar year 2001 for male members aged 18 years or older. Medical claims for MCO members who had sildenafil claims were used to identify comorbid diseases and categorize patients by degree of cardiovascular risk. High risk was defined as having at least 1 medical claim with a diagnosis of diabetes mellitus, ischemic heart disease, abdominal aortic aneurysm, or peripheral arterial disease, and medium risk was defined as not having any diagnosis in the high-risk category but at least 1 cardiovascular risk factor that included smoking, hypertension, hypercholesterolemia, family history of premature coronary heart disease, or being aged 45 years or older.. There were 67,914 pharmacy claims for sildenafil during 2001 for 20,281 MCO members, an average of 3.3 pharmacy claims per patient. The prevalence of sildenafil use was 54.1 per 1,000 male MCO members aged 18 years or older. The total allowed charges for sildenafil pharmacy claims in 2001 were 3.56 million US dollars, of which patients paid 26.6% in average cost-share, and the net MCO cost per member per month (PMPM) was 0.18 US dollars. A total of 1,681 patients (8.3%) exceeded their quantity restrictions for sildenafil tablets in 2001, of which 1,362 (81.0%) paid cash and 319 (19.0%, or 1.6% of all sildenafil users) appealed and received approval from the MCO for additional sildenafil tablets beyond the restriction of 6 tablets per month. Medical claims were available for 15,644 sildenafil patients (77.1%), and 12,720 sildenafil users (81.3% of those with medical claims) were judged to be at high or medium cardiovascular risk.. A quantity limit of 6 tablets of sildenafil per 30-day period was associated with a drug cost to users and the MCO of 0.25 US dollars PMPM. Sildenafil users paid an average cost-share of 26.6%, resulting in a net drug cost of 0.18 US dollars PMPM to the MCO.

Topics: Administration, Oral; Adult; Aged; Cardiovascular Diseases; Cost Control; Drug Costs; Drug Prescriptions; Drug Utilization; Erectile Dysfunction; Humans; Insurance Claim Review; Insurance, Pharmaceutical Services; Male; Managed Care Programs; Middle Aged; Phosphodiesterase Inhibitors; Piperazines; Purines; Risk Factors; Sildenafil Citrate; Sulfones; Time Factors

Infants infected with Bordetella pertussis in the first few weeks of life are at risk of death from 'overwhelming cardiovascular compromise despite intensive care support'. The mechanisms of this severe disease are not completely understood. Three case histories, including that of one infant who survived, are presented. Two of the patients died despite intensive therapy with pressors and, in one child, milrinone. The third child survived following treatment with nitric oxide and sildenafil. Hence, sildenafil in combination with nitric oxide shows promise as a therapy for the haemodynamic consequences of pertussis toxaemia and this should prompt clinical trials for their efficacy for this condition.

Topics: Bordetella pertussis; Cardiovascular Diseases; Drug Therapy, Combination; Humans; Infant; Infant, Newborn; Male; Nitric Oxide; Piperazines; Purines; Sildenafil Citrate; Sulfones; Vasodilator Agents; Whooping Cough

The present study assesses the effectiveness of our progressive treatment program for erectile dysfunction in patients with cardiovascular diseases. The study sample included 453 patients aged 36 to 91 years. Therapy in all patients was begun with sildenafil citrate 25 to 100 mg. Those with contraindications, drug adverse effects, or a negative response (erection insufficient for vaginal penetration) were given intracavernous injections of a cocktail of vasoactive drugs (dimix, trimix, or quadmix), followed by the addition of sildenafil citrate to the trimix in case of failure, and then a penile prosthesis. Patients were followed for 2 years; in cases of treatment ineffectiveness during follow-up, drug dosages were increased or a penile prosthesis was suggested. Sildenafil citrate was offered to 417 patients of whom 205 (49.2%) responded positively. The remaining 248 patients received intracavernous injections: 135 (54.4%) had a positive response to the dimix, 85 (75.2%) to the trimix, and 16 (57.1%) to the quadmix. Four of the other 12 patients (0.9%) responded to sildanefil citrate + trimix, and 2 (0.4%) agreed to a penile prosthesis. At the 2-year follow-up of 447 patients, 131 (29.3%) were successfully treated with sildanefil citrate, 92 (20.6%) with dimix, 122 (27.3%) with trimix, 12 (2.7%) with quadmix, and 2 (0.4%) with sildanefil citrate + trimix; 5 patients (1.1%) had a penile implant. Forty-eight patients (10.7%) achieved spontaneous erection, of whom 46 were taking aspirin. Twenty-six patients (5.8%) stopped treatment because of health and family reasons and 9 (2%) had a negative response. Our progressive treatment program for erectile dysfunction has a high success rate in patients with cardiovascular disease: Overall, 98.7% achieved an erection sufficient for vaginal penetration immediately after the trial and 92.2% on follow-up; 10.7% achieved spontaneous erections.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Cardiovascular Diseases; Drug Administration Schedule; Erectile Dysfunction; Helium; Humans; Injections; Male; Middle Aged; Nitrogen; Oxygen; Penile Prosthesis; Piperazines; Purines; Severity of Illness Index; Sildenafil Citrate; Sulfones; Treatment Outcome; Vasodilator Agents

Erectile dysfunction (ED) is frequently observed in male cardiovascular disease (CVD) patients, creating concern about cardiac risk of their sexual activity, and their therapeutic use of sildenafil. Relatively little information exists about sildenafil effects on exercise testing, hemodynamic parameters or on occurrence of ventricular arrhythmias during normal activities in CVD patients.. Single, oral doses of sildenafil do not significantly affect exercise-induced changes in hemodynamic parameters or occurrence of arrhythmias in ED/CVD patients.. ED patients, with or without CVD, were enrolled in one of two studies. In the first, patients underwent standard (Bruce Protocol) treadmill tests; an initial control test was followed 1 hour later by administration of 100mg oral sildenafil. After another hour, they underwent a second treadmill test. Systolic and diastolic blood pressure (SBP and DBP), heart rate, and double product were determined for each evaluation at pretest, maximum stress, and recovery. In the second, Holter ambulatory ECGs were recorded 5 hours before and 6 hours after 100mg oral sildenafil administration.. Sildenafil had no clinically significant effects on exercise-induced changes in hemodynamic parameters in cardiac patients and only slight, clinically insignificant effects in noncardiac patients. ECG showed sildenafil did not affect incidence of ventricular arrhythmias.. Sildenafil does not alter hemodynamic response to exercise or change incidence of ventricular arrhythmias in men with CVD and ED. These results suggest that, when used in accordance with prescribing information and current treatment guidelines, sildenafil should be safe for most patients with both these conditions.

Topics: Adult; Aged; Arrhythmias, Cardiac; Blood Pressure; Cardiovascular Diseases; Echocardiography; Electrocardiography; Electrocardiography, Ambulatory; Erectile Dysfunction; Exercise Test; Heart; Heart Rate; Humans; Male; Middle Aged; Piperazines; Purines; Sildenafil Citrate; Sulfones; Vasodilator Agents

After the acute phase, a patient who is diagnosed with cardiac or vascular disease becomes "chronically ill". This patient will then still spend many years without symptoms or impairments. One day, a percentage of such patients will be confronted with the problem of erectile dysfunction. Various studies have demonstrated that this problem occurs with a higher frequency in patients with cardiovascular diseases, in particular when they have to be treated for hypertension, diabetes mellitus or dyslipidemia. Very rarely are stenoses or occlusions found in the arteries responsible for penile circulation. More recent data indicates that a diffuse anomaly of the vascular endothelium is present, for which erectile dysfunction is a marker. Nowadays, medical care has achieved a better degree of standardization, not only thanks to knowledge about the effects of cardiovascular medication, but also because the physician can now prescribe drugs that treat erectile dysfunction.

Topics: Cardiovascular Agents; Cardiovascular Diseases; Chronic Disease; Endothelium, Vascular; Erectile Dysfunction; Humans; Impotence, Vasculogenic; Male; Piperazines; Purines; Risk Factors; Sildenafil Citrate; Sulfones; Vasodilator Agents

Topics: Cardiovascular Diseases; Clinical Trials as Topic; Cohort Studies; Contraindications; Double-Blind Method; Humans; Hypertension; Male; Middle Aged; Piperazines; Placebos; Primary Health Care; Purines; Risk Factors; Sildenafil Citrate; Sulfones; United Kingdom; Vasodilator Agents

Topics: Cardiovascular Diseases; Cause of Death; Drug Overdose; Humans; Male; Middle Aged; Piperazines; Product Surveillance, Postmarketing; Purines; Randomized Controlled Trials as Topic; Sildenafil Citrate; Sulfones; Vasodilator Agents

Sildenafil citrate is a potent donor of nitric oxide that has been proved to be effective for the treatment of male erectile dysfunction, but it has been contraindicated in patients with cardiovascular diseases, because of sudden death occurred to some of them. Based on the known vasodilator effect of nitrix oxide, effect that should be beneficial for some cardiomyopathies, this work was carried out in order to prove the cardiovascular effects of sildenafil citrate on: 1) heart rate, rhythm and repolarization changes on the ecg; 2) systolic and diastolic arterial blood pressure; 3) left ventricular systolic function and 4) right and left ventricular diastolic function in 26 patients suffering from the following cardiomyopathies: chronic Chagas's and diabetic cardioneuromyopathies, hypertensive and/or hypertrophic cardiomyopathies with or without chronic congestive heart failure.. sildenafil citrate 50 mgr after a single oral dose: 1) improved the ecg findings in some patients, worsening the basal ecg in none of the studied patients; 2) significantly reduced systolic and diastolic arterial blood pressure being such reduction very strong in those with basal high level 3) significantly improved left ventricular systolic function in those patients with basal reduced function and 4) Right ventricular diastolic function evaluation: Sildenafil citrate 50 mgr significantly modified to normal pattern the E/A basal altered ratio in those patients with the inverted pattern as well as in those with restrictive pattern of tricupid diastolic influx to the right ventricle during the echo-duplex interrogation (p < 0.0001) 5) Left ventricular diastolic function evaluation: Sildenafil citrate 50 mgr significantly modified to normal pattern the E/A basal altered ratio in those patients with the inverted pattern as well as in those with restrictive pattern of mitral diastolic influx to the left ventricle, during the echo-duplex interrogation (p 0 <.0001).. Based on the above findings it is feasible to propose the use of sildenafil citrate to treat patients with cardiovascular diseases, with exclusion of severe obstructive coronary artery disease, hypertrophic subaortic stenosis and patients with funduscopic alterations that may be affected by a significant and acute increase of flow within the ophthalmic arteries. The right ventricular diastolic changes observed with Sildenafil Citrate may be useful in patients with abnormal right ventricular compliance such as pulmonary stenosis or hypertension.

Topics: Blood Pressure; Cardiovascular Diseases; Chagas Disease; Diabetic Angiopathies; Electrocardiography; Female; Heart Failure; Heart Rate; Humans; Male; Piperazines; Purines; Sildenafil Citrate; Sulfones; Time Factors; Vasodilator Agents; Ventricular Function

Topics: Adult; Aged; Aged, 80 and over; Cardiovascular Diseases; Coronary Angiography; Erectile Dysfunction; Humans; Male; Middle Aged; Piperazines; Purines; Sildenafil Citrate; Sulfones; Vasodilator Agents

The aim of this study was to evaluate the effectiveness of a progressive program for the treatment of erectile dysfunction in patients with cardiovascular disease in whom sildenafil citrate (Viagra) was not an option. The study population included 106 patients selected from 267 with cardiovascular disease. The intracavernous injection program consisted of three protocols of increasingly complex combinations of vasoactive drugs, papaverine, phentolamine, prostaglandin E1 and atropine sulfate. Patients who failed the first protocol were switched to the second, and those who failed the second were switched to the third. A positive response was defined as an erection sufficient for vaginal penetration. A positive response was achieved on protocol I in 61 of the 106 patients (57.5%); protocol II in 32 of the remaining 45 patients (71.1%); and protocol III in seven of the remaining 13 patients (53.8%); the total success rate was 94.3%. These 100 patients were included in the 1-year follow-up, and 90 reported successful coitus at the end of that period: 79 patients (87.8%) with intracavernous injection and 11 (12.2%) without injection. The remaining 10 patients (10%) dropped out of the program, seven (7.0%) for health or marital reasons and three (3.0%) because of treatment failure. We conclude that a progressive program of intracavernous injections of vasoactive drugs may be a good alternative for the treatment of erectile dysfunction in patients with cardiovascular disease.

Topics: Adrenergic alpha-Antagonists; Adult; Aged; Aged, 80 and over; Alprostadil; Atropine; Cardiovascular Diseases; Coitus; Contraindications; Drug Combinations; Erectile Dysfunction; Follow-Up Studies; Humans; Injections; Male; Middle Aged; Muscarinic Antagonists; Papaverine; Penis; Phentolamine; Piperazines; Purines; Retreatment; Sildenafil Citrate; Sulfones; Treatment Failure; Vasodilator Agents

Topics: Cardiovascular Diseases; Coitus; Exercise; Humans; Impotence, Vasculogenic; Male; Phosphodiesterase Inhibitors; Piperazines; Purines; Sildenafil Citrate; Sulfones

Sildenafil is a medication increasingly prescribed to improve sexual function in patients who have erectile dysfunction. Because a major contraindication to the use of sildenafil is a history of coronary disease and the concomitant use of nitrates, it becomes increasingly important for cardiologists to prescribe this medication. We evaluated the nature of discussions in all 70 patients for whom sildenafil was prescribed in a cardiology practice between April and July 1998. We used a standardized questionnaire to determine the patients' perspective on the sexual history and the extent to which they wanted their physicians to take a detailed history about sexuality. A separate chart review evaluated the nature of physicians' discussions about sexual functioning before sildenafil was prescribed. Fifty-five of the 70 patients (79%) responded to the survey. The majority of patients (98%) felt that physicians should talk with patients about sexual functioning. However, only 73% of patients believed their doctor was comfortable talking with them about this subject. Sixty percent of patients reported that their doctor had ever talked with them about erectile function and only 15% had ever had a discussion with their doctors about specific difficulties during intercourse. Based on the results of the chart review, only 24% of the patients ever specifically discussed the used of sildenafil with their physician prior to the time that it was prescribed. The results of the study suggest that patients with coronary disease erectile dysfunction are comfortable talking with their physicians about sexual functioning, but these conversations occur infrequently.

Topics: Aged; Aged, 80 and over; Cardiovascular Diseases; Contraindications; Coronary Disease; Erectile Dysfunction; Humans; Male; Middle Aged; Patient Compliance; Phosphodiesterase Inhibitors; Piperazines; Practice Patterns, Physicians'; Purines; Quality of Life; Sexuality; Sildenafil Citrate; Sulfones; Surveys and Questionnaires

Topics: Angiotensin II; Carbolines; Cardiovascular Diseases; Delayed-Action Preparations; Erectile Dysfunction; Humans; Male; Phosphodiesterase Inhibitors; Piperazines; Purines; Sildenafil Citrate; Sulfones; Tadalafil

Topics: Cardiovascular Diseases; Cost-Benefit Analysis; Humans; Phosphodiesterase Inhibitors; Piperazines; Purines; Risk Factors; Sildenafil Citrate; Sulfones

Topics: 3',5'-Cyclic-GMP Phosphodiesterases; Adolescent; Adult; Aged; Aged, 80 and over; Cardiovascular Diseases; Cause of Death; Drug Prescriptions; England; Erectile Dysfunction; Follow-Up Studies; Humans; Male; Middle Aged; Phosphodiesterase Inhibitors; Piperazines; Purines; Sildenafil Citrate; Sulfones; Survival Rate

Topics: Cardiovascular Diseases; England; Erectile Dysfunction; Health Services Accessibility; Humans; Male; Phosphodiesterase Inhibitors; Piperazines; Purines; Sildenafil Citrate; State Medicine; Sulfones

Topics: Cardiovascular Diseases; Contraindications; Drug Labeling; Humans; Male; Phosphodiesterase Inhibitors; Piperazines; Purines; Sildenafil Citrate; Sulfones

Topics: 3',5'-Cyclic-GMP Phosphodiesterases; Adult; Autonomic Nervous System; Blood Pressure; Cardiovascular Diseases; Central Nervous System; Cyclic Nucleotide Phosphodiesterases, Type 5; Heart Rate; Humans; Isoenzymes; Male; Muscle, Smooth; Organ Specificity; Piperazines; Purines; Sildenafil Citrate; Stress, Physiological; Sulfones; Sympathetic Nervous System

Topics: Cardiovascular Diseases; Humans; Male; Phosphodiesterase Inhibitors; Piperazines; Product Surveillance, Postmarketing; Purines; Sildenafil Citrate; Sulfones; United States; United States Food and Drug Administration

Topics: 3',5'-Cyclic-GMP Phosphodiesterases; Administration, Oral; Adult; Aged; Cardiovascular Diseases; Contraindications; Erectile Dysfunction; Female; Humans; Male; Menopause; Middle Aged; Orgasm; Phosphodiesterase Inhibitors; Piperazines; Purines; Risk Factors; Sexual Dysfunction, Physiological; Sexual Partners; Sildenafil Citrate; Sulfones

Topics: Cardiovascular Diseases; Contraindications; Erectile Dysfunction; Humans; Hypotension; Male; Nitrates; Phosphodiesterase Inhibitors; Piperazines; Purines; Risk Factors; Sildenafil Citrate; Sulfones

Topics: Cardiovascular Diseases; Drug Interactions; Erectile Dysfunction; Humans; Male; Phosphodiesterase Inhibitors; Piperazines; Purines; Sildenafil Citrate; Sulfones

The most common physical risk factors for erectile dysfunction (ED) are atherosclerosis, heart disease, hypertension and diabetes. Since accessibility to easy and efficacy drug for ED therapy, GPs are increasingly at the front line in the management of ED and are often best-placed to discuss this problem with cardiovascular male patients. This consensus aims to provide practical advice on the management of ED in patients with diagnosed cardiovascular disease and also addresses the assessment of the cardiovascular risk in restoring sexual activity in these patients. A risk assessment algorithm has been drawn up to aid clinicians in deciding the level of cardiovascular risk that would be associated with a return of sexual activity as well as criteria for referral to specialists for further cardiac evaluation. Treatment options are briefly reviewed and follow-up process identified.

Topics: Adult; Cardiovascular Diseases; Erectile Dysfunction; Family Practice; Humans; Male; Phosphodiesterase Inhibitors; Piperazines; Practice Guidelines as Topic; Purines; Referral and Consultation; Risk Assessment; Sildenafil Citrate; Sulfones

Topics: 3',5'-Cyclic-GMP Phosphodiesterases; Adult; Aged; Cardiovascular Diseases; Contraindications; Diabetes Complications; Enzyme Inhibitors; Erectile Dysfunction; Humans; Male; Middle Aged; Piperazines; Purines; Risk Assessment; Sildenafil Citrate; Sulfones

Topics: 3',5'-Cyclic-GMP Phosphodiesterases; Cardiovascular Diseases; Enzyme Inhibitors; Erectile Dysfunction; Female; Humans; Male; Middle Aged; Piperazines; Purines; Sildenafil Citrate; Sulfones

Topics: Cardiovascular Diseases; Contraindications; Death, Sudden, Cardiac; Erectile Dysfunction; Humans; Male; Phosphodiesterase Inhibitors; Piperazines; Purines; Sildenafil Citrate; Sulfones

Topics: Cardiovascular Diseases; Cardiovascular System; Humans; Piperazines; Purines; Sildenafil Citrate; Sulfones; Vasodilator Agents

Since the release of sildenafil citrate (Viagra), increasing numbers of patients are seeking treatment for erectile dysfunction (ED). Many of the risk factors for ED are the same as those for cardiac disease. Sildenafil citrate is a highly effective oral agent for ED. It is absolutely contraindicated in patients receiving organic nitrates. The issue of cardiac deaths associated with sildenafil citrate and ways of potentially minimizing these cases are discussed.

Topics: Cardiovascular Diseases; Contraindications; Diabetes Complications; Enzyme Inhibitors; Erectile Dysfunction; Humans; Male; Penile Erection; Piperazines; Purines; Risk Factors; Sildenafil Citrate; Sulfones

Topics: Canada; Cardiovascular Diseases; Enzyme Inhibitors; Erectile Dysfunction; Humans; Male; Piperazines; Purines; Sildenafil Citrate; Sulfones; United States

Topics: Canada; Cardiology; Cardiovascular Diseases; Erectile Dysfunction; Humans; Male; Phosphodiesterase Inhibitors; Piperazines; Purines; Sildenafil Citrate; Societies, Medical; Sulfones

Topics: Cardiovascular Diseases; Contraindications; Decision Trees; Erectile Dysfunction; Humans; Male; Nitrates; Phosphodiesterase Inhibitors; Piperazines; Purines; Sildenafil Citrate; Sulfones

Topics: Alprostadil; Cardiovascular Diseases; Erectile Dysfunction; Humans; Intraoperative Complications; Male; Phosphodiesterase Inhibitors; Piperazines; Prostate; Prostatectomy; Purines; Risk Factors; Sildenafil Citrate; Sulfones; Vasodilator Agents

Topics: Cardiovascular Diseases; Contraindications; Guidelines as Topic; Humans; Male; Phosphodiesterase Inhibitors; Piperazines; Purines; Sildenafil Citrate; Sulfones

The introduction of sildenafil (Viagra) for the treatment of erection disorders has received much international attention. In the USA the prevalence of severe erection disorder amounts to 10% for men aged 40-70 years, which is much higher than was expected, in the Netherlands as well. This is probably due to embarassment with the condition and the absence of simple treatment. With the advent of sildenafil the problem of erection disorder is now openly discussed. An interview investigation in Leiden, the Netherlands, showed that two-thirds of men with erection problems (n = 200) who volunteered to participate in a relevant study, had consulted to a physician before; one-third of the volunteers were interested in using an erection pill, one-third also in other treatments, and one-third wanted to be treated by any method. These figures indicate that most men already take their problem seriously. As age is the main contributing factor to erection disorder, the safety of sildenafil in the elderly is a point of concern. Nitrate use is an absolute contraindication, poor cardiovascular condition is a relative contraindication. Sildenafil will probably become the drug of choice for the treatment of erection disorder. It constitutes a major step forward.

Topics: Adult; Age Factors; Aged; Cardiovascular Diseases; Contraindications; Drug Interactions; Erectile Dysfunction; Humans; Male; Middle Aged; Nitrates; Piperazines; Purines; Sildenafil Citrate; Sulfones