Phosphodiesterase Type 5 Inhibitors Improve Endothelial Function and May Benefit Cardiovascular Conditions
Heart Institute, Good Samaritan Hospital, Los Angeles, Calif. The American journal of medicine
(Impact Factor: 5).
03/2013; 126(3):192-9. DOI: 10.1016/j.amjmed.2012.08.015
The effects of phosphodiesterase type 5 inhibitors on vasodilation mediated via nitric oxide-cyclic guanosine monophosphate are well described. Less is known about other mechanisms through which phosphodiesterase type 5 inhibitors benefit endothelial function, including normalization of serum biomarkers, increased levels of endothelial progenitor cells, ischemia-reperfusion protection mechanisms, and other actions specific to patients with diabetes. These various mechanisms are reviewed. Their impact on several cardiovascular diseases, including erectile dysfunction, pulmonary hypertension, heart failure, high-altitude pulmonary edema, Raynaud's phenomenon, coronary artery disease, diabetes, and atherosclerosis, is presented.
Available from: PubMed Central
- "Although the etiology of DM-induced ED is multifactorial and still unknown, endothelial dysfunction is thought to be one of the key factors. Patients with DM and ED often have severe endothelial dysfunction and respond poorly to oral phosphodiesterase (PDE)5 inhibitors . Tadalafil is a PDE5 inhibitor that is safe and efficacious for treating ED across a variety of clinical populations, including patients with many risk factors . "
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ABSTRACT: We studied the relative importance of high-sensitivity C-reactive protein (hs-CRP) concentrations in patients with erectile dysfunction (ED) and diabetes and determined whether the hs-CRP level predicts the response to treatment with 5 mg tadalafil once daily.
We enrolled 102 men (aged 40-60 years) with diabetes and ED. All patients completed the International Index of Erectile Function (IIEF) questionnaire and were given 5 mg tadalafil daily. The IIEF and serum hs-CRP levels in patients and healthy controls and in patient responders and nonresponders to 5 mg tadalafil once daily were compared.
Median age was 53.2 years (range, 45 to 62 years) in patients and 55.6 years (range, 47 to 64 years) in healthy controls (p=0.158). The median duration of diabetes was 54.3 months (range, 34 to 70 months). The median IIEF and hs-CRP level were 12.1 (range, 5 to 20) and 0.21 mg/dL (range, 0.05 to 0.6 mg/dL) in patients and 28.2 (range, 13 to 31) and 0.09 mg/dL (range, 0.04 to 0.2 mg/dL) in the controls, respectively (pIIEF=0.000, pCRP=0.031). After tadalafil treatment, 71 patients (69.6%) achieved an erection sufficient for sexual intercourse, whereas 31 (30.4%) did not. The median age of the tadalafil nonresponders was 56.2 years (range, 45 to 64 years) and that of the responders was 51.3 years (range, 42 to 62 years; p=0.065). Median hs-CRP levels were 0.31 mg/dL (range, 0.18 to 0.62 mg/dL) in nonresponders and 0.14 mg/dL (range, 0.09 to 0.4 mg/dL) in responders, respectively (p=0.028).
Serum hs-CRP was significantly higher in patients with ED and diabetes mellitus than in patients without ED. A significant correlation was observed between serum hs-CRP levels, the degree of ED, and responsiveness to tadalafil.
Korean journal of urology 12/2013; 54(12):858-64. DOI:10.4111/kju.2013.54.12.858
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Management of chronic angina has evolved dramatically in the last few decades with several options for pharmacotherapy outlined in various evidence-based guidelines.
There is a growing list of drugs that are currently being investigated for treatment of chronic angina. These also include several herbal medications, which are now being scientifically evaluated as potential alternative or even adjunctive therapy for angina. Gene- and cell-based therapies have opened yet another avenue for management of chronic refractory angina in 'no-option' patients who are not candidates for either percutaneous or surgical revascularization and are on optimal medical therapy. An extensive review of literature using PUBMED, Cochrane database, clinical trial databases of the USA and European Union was done and summarized in this review. This review will attempt to discuss the traditional as well as novel therapeutic agents for angina.
Several pharmacological and non-pharmacological therapeutic options are now available for treatment and management of chronic refractory angina. Renewed interest in traditional therapies and cell- and gene-based modalities with targeted drug delivery systems will open the doors for personalized therapy for patients with chronic refractory angina.
Expert Opinion on Pharmacotherapy 09/2013; 14(17). DOI:10.1517/14656566.2013.834329 · 3.53 Impact Factor
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ABSTRACT: Clinical trials have evaluated the use of phosphodiesterase (PDE) 5 inhibitors sildenafil as a potential adjunct in the treatment of heart failure (HF) with mixed results. Thus, we undertook a meta-analysis to evaluate the clinical viability of sildenafil in HF.
Relevant studies were searched and identified in the MEDLINE and EMBASE databases. Randomized clinical trials (RCT) comparing sildenafil to placebo, in heart failure patients, reporting at least one outcome of interest were included. Data were extracted regarding the characteristics and clinical outcomes.
We identified 9 RCTs enrolling 612 HF patients. There were no significant differences in adverse events between sildenafil group and placebo group (RR=1.10, 95% CI=0.74 to 1.65, P=0.41), whereas sildenafil therapy was associated with a marked improvement in hemodynamic parameter peak VO2 (MD=3.25, 95% CI=2.07 to 4.42, P<0.00001) in HF with reduced ejection fraction (HFrEF) patients but not in HF with preserved ejection fraction (HFpEF) patients. Also, sildenafil therapy improved VO2 at anaerobic threshold (AT) (MD=3.47, 95% CI=1.68 to 5.27, P=0.0002), VE/VCO2 slope (MD=-7.06, 95% CI=-8.93 to -5.19, P<0.00001) and LV ejection fraction (MD=5.43, 95% CI=3.66 to 7.20, P<0.00001) compared to placebo in HF patients, which had no impact on blood pressure and heart rate. For quality of life (emotional function, fatigue and breathlessness), there was no significant difference between the two groups.
Sildenafil improved hemodynamic parameters particularly in HFrEF patients when compared to placebo, with no increase in adverse events. Sildenafil treatment was well tolerated and had no impact on quality of life.
International journal of cardiology 01/2014; 172(3). DOI:10.1016/j.ijcard.2014.01.102 · 4.04 Impact Factor
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