PDE5 Inhibitors In Patients Research Articles

Safety of Phosphodiesterase-5 Inhibitors in Valvular Heart Disease.

Erectile dysfunction is a common entity in clinical practice. Primary erectile dysfunction, not related to vasculopathy or psychiatric disorder, can be readily treated with phosphodiesterase inhibitors. These drugs have many physiologic effects that can alter a patient's hemodynamic profile considerably, especially in the presence of concomitant structural heart disease, specifically valvular heart disease. Although some contraindications to the use of PDE5 inhibitors in patients with cardiovascular disease are defined, the effect of these drugs in the presence of valvular heart disease is not well documented. The purpose of this review is to analyze the data regarding the safety of PDE5 inhibitors in patients with valvular heart disease.

PS-05-004 Discontinuation of dapoxetine treatment in patients with premature ejaculation: A 2-year prospective observational study

Although dapoxetine is the only oral pharmacological agent approved for the treatment of premature ejaculation (PE) and is very effective, its discontinuation rate is high compared to PDE5 inhibitors in patients with erectile dysfunction (ED). This study assessed the discontinuation rate of dapoxetine treatment in patients with PE and the reasons for discontinuation a clinical setting. The study enrolled 182 consecutive patients (mean age 38.2 (range 19–63) years). The PE type (life-long or acquired), self-estimated intravaginal ejaculation latency time (IELT), International Index of Erectile Function-Erectile Function Domain (IIEF-EF) questionnaire, and medical history were checked in all patients. The patients were evaluated 1, 3, 6, 12, and 24 months after initiating therapy regarding the treatment status and the reasons for treatment discontinuation in the case of discontinuation. We compared the discontinuation rates with various parameters and the time interval. Of the patients, 9.9% were continuing treatment after 2 years. The discontinuation rate at 1, 3, 6, 12, and 24 months was 26.4, 35.2, 17.6, 8.2, and 2.7%, respectively. Cumulatively, 79.1% of the patients discontinued the treatment within 6 months. After 12 months, however, the discontinuation rate dropped sharply. The reasons for discontinuation were cost (29.9%), disappointment that PE is not a curable disease and dapoxetine was needed whenever he had sex (25%), side effects (11.6%), low efficacy (9.8%), to seek other treatment options (5.5%), and unknown (18.3%). Patients with acquired PE (vs. life-long), IELT >2 min before treatment, older than 50 years, taking PDE-5 inhibitors, and IIEF-EF <26 tended to discontinue early and had high drop-out rates.

Erectile dysfunction and its management in patients with diabetes mellitus.

Diabetes can be described as a syndrome of multiple closely related conditions induced by a chronic state of hyperglycaemia resulting from defective insulin secretion, insulin action or both. Chronic complications associated with diabetes (including neuropathy, vascular disease, nephropathy and retinopathy) are common, and of these, erectile dysfunction (ED) deserves special attention. ED and its correlation with cardiovascular disease require careful evaluation and appropriate treatment. PDE5 inhibitors (PDE5is) are an important tool for the treatment of ED, with new drugs coming onto the market since the late 90s. This review offers an overview of PDE5is and their use in treating ED in diabetes. We underline the differences between different types of PDE5i, focusing on available doses, duration of action, T ½, side effects and selectivity profiles in relation to patients with diabetes. We also discuss the link between diabetes and ED in presence of various associated cofactors (obesity, hypertension and its pharmacological treatments, atherosclerosis, hyperhomocysteinaemia, neuropathy, nephropathy, hypogonadism and depression). Finally a number of past and ongoing clinical trials on the use of PDE5is in patients with diabetes are presented to offer an overview of the appropriate treatment of ED in this condition.

AB142. Discontinuation of dapoxetine treatment in patients with premature ejaculation: a 2-year prospective observational study

ObjectiveAlthough dapoxetine is the only oral pharmacological agent approved for the treatment of premature ejaculation (PE) and is very effective, its discontinuation rate is high compared to PDE5 inhibitors in patients with erectile dysfunction (ED). This study assessed the discontinuation rate of dapoxetine treatment in patients with PE and the reasons for discontinuation a clinical setting.MethodsThe study enrolled 182 consecutive patients [mean age, 38.2 (range, 19-63) years] between October 1, 2011 and September 30, 2013. The PE type (life-long or acquired), self-estimated intravaginal ejaculation latency time (IELT), International Index of Erectile Function-Erectile Function Domain (IIEF-EF) questionnaire, and medical history were checked in all patients. The patients were evaluated 1, 3, 6, 12, and 24 months after initiating therapy regarding the treatment status and the reasons for treatment discontinuation in the case of discontinuation. We compared the discontinuation rates with various parameters and the time interval.ResultsOf the patients, 9.9% were continuing treatment after 2 years. The discontinuation rate at 1, 3, 6, 12, and 24 months was 26.4%, 35.2%, 17.6%, 8.2%, and 2.7%, respectively. Cumulatively, 79.1% of the patients discontinued the treatment within 6 months. After 12 months, however, the discontinuation rate dropped sharply. The reasons for discontinuation were cost (29.9%), disappointment that PE is not a curable disease and dapoxetine was needed whenever he had sex (25%), side effects (11.6%), low efficacy (9.8%), to seek other treatment options (5.5%), and unknown (18.3%). Patients with acquired PE (vs. life-long), IELT >2 min before treatment, older than 50 years, taking PDE-5 inhibitors, and IIEF-EF <26 tended to discontinue early and had high drop-out rates.ConclusionsOf the patients, 9.9% were continuing treatment after 2 years. The discontinuation rate at 1, 3, 6, 12, and 24 months was 26.4%, 35.2%, 17.6%, 8.2%, and 2.7%, respectively. Cumulatively, 79.1% of the patients discontinued the treatment within 6 months. After 12 months, however, the discontinuation rate dropped sharply. The reasons for discontinuation were cost (29.9%), disappointment that PE is not a curable disease and dapoxetine was needed whenever he had sex (25%), side effects (11.6%), low efficacy (9.8%), to seek other treatment options (5.5%), and unknown (18.3%). Patients with acquired PE (vs. life-long), IELT >2 min before treatment, older than 50 years, taking PDE-5 inhibitors, and IIEF-EF <26 tended to discontinue early and had high drop-out rates.

FRI0380 An indirect comparisons analysis of prostacyclins, endothelin receptor antagonists and phosphodiesterase inhibitors to evaluate for differences between the treatment for primary and secondary pulmonary hypertension

BackgroundDifferences in the pathogenesis between primary pulmonary hypertension (PpHTN) and secondary pulmonary hypertension (SpHTN) suggest autoimmunity plays a pivotal role in the latter. Connective tissue diseases (CTD) are the most...

Synergetic effect of testosterone and phophodiesterase-5 inhibitors

Testosterone deficiency seems to impair the clinical response tophophodiesterase-5 (PDE-5) inhibitors in patients with erectile dysfunction (ED). In hypogonadal men, testosterone repletion was associated with enhanced sexual function in patients who failed initial treatment with sildenafil or tadalafil. We conducted a systematic review of studies that evaluated combination therapy of testosterone and PDE-5 inhibitors in patients with ED and low, low-normal testosterone levels who failed monotherapy. The studies we examine are heterogeneous with several methodological drawbacks and that, overall, the addition of testosterone to PDE-5 inhibitors might benefit patients with ED associated with testosterone &lt;300 ng/dL (10.4 nmol/L) who failed monotherapy. Further studies, with a randomized placebo-controlled and double blind design, are needed to describe the appropriate target patient group, testosterone cut-off and to define the optimal dose and duration of combination therapy.

Phosphodiesterase Inhibitors, Congestive Heart Failure, and Sudden Death: Time for Re‐Evaluation

A 42-year-old diabetic man was admitted with systolic heart failure and pulmonary hypertension being treated with sildenafil for the previous year. With an increase in creatinine, he experienced 3 episodes of ventricular tachycardia and ventricular fibrillation. Withdrawal of the phosphodiesterase (PDE) inhibitor resulted in no further episodes of dysrhythmias. The basic pharmacology of PDE inhibitors is presented and the use of PDE-3 inhibitors for the treatment of heart failure causing an increase in sudden death is also reviewed. There have been several cases of sudden death associated with sildenafil use and with its increasing use in patients with severe pulmonary hypertension and decompensated heart failure. The authors also reviewed the electrophysiologic effects of PDE-5 inhibitors associated with their use. The crossover between PDE-3 and PDE-5 inhibitors is also discussed and caution is urged when contemplating the use of PDE-5 inhibitors in patients with systolic heart failure and pulmonary hypertension.

Arterial methemoglobin level predicts therapeutic effectiveness of the PDE5 inhibitors in patients with in idiopathic pulmonary arterial hypertension

Background The PDE5 inhibitors are emerging as novel therapeutic tools in patients with idiopathic pulmonary arterial hypertension (PAH). However, the response to the PDE5 inhibitors varies among patients. The PDE inhibitor augments and prolongs the vasodilator effect of NO. Thus, therapeutic effectiveness of the PDE inhibitors relies on the ability of pulmonary vascular endothelial cells to produce NO. Hemoglobin binds to NO with great affinity and forms methemglobin by oxidation in the erythrocyte. We hypothesized that methemoglobin level is correlated positively with the capacity of NO production in pulmonary vascular endothelial cells and can be used as a biomarker for prediction of therapeutic response to the PDE5 inhibitors.

C32 The difference in treatment efficacy between long-acting and short-acting PDE5 inhibitors in patients with erectile dysfunction

C32 The difference in treatment efficacy between long-acting and short-acting PDE5 inhibitors in patients with erectile dysfunction

Acute Hemodynamic Effects of Intravenous Sildenafil Citrate in Congestive Heart Failure: Comparison of Phosphodiesterase Type-3 and -5 Inhibition

The reversibility of elevated pulmonary vascular resistance in heart failure bears an important relation to outcome after cardiac transplantation. The phosphodiesterase 3 (PDE3) and PDE5 inhibitors both increase levels of cyclic nucleotides in the vascular smooth muscle, causing vasodilatation. PDE3 inhibitors also have direct inotropic effects. We contrasted the acute hemodynamic responses to intravenous PDE3 and PDE5 inhibitors in patients with congestive cardiac failure to assess their relative suitability for reversibility testing in this setting. Thirty patients undergoing assessment for cardiac transplantation underwent right heart catheterization. Patients were randomized to receive an intravenous bolus of milrinone (0.05 mg/kg) or sildenafil citrate at a high (0.43 mg/kg) or low dose (0.05 mg/kg). Differences between low- and high-dose sildenafil were not significant. Both agents caused similar reductions in systemic and pulmonary vascular resistance. Milrinone caused significantly greater reductions in pulmonary artery wedge and mean pulmonary artery pressure, and increases in heart rate. In all study groups, greater increases in cardiac index (>25%) were seen in patients with a higher pulmonary artery wedge pressure at baseline (29 +/- 1 vs 20 +/- 2 mm Hg; p < 0.001). In end-stage congestive cardiac failure, intravenous milrinone and sildenafil both cause similar reductions in systemic and pulmonary vascular resistance; however, milrinone has more cardiac selective effects on left ventricular filling and heart rate. Both agents appear to have a suitable hemodynamic profile for testing of reversibility of secondary pulmonary hypertension in congestive cardiac failure. Larger studies are needed to confirm these results.