Safety and Efficacy of Vardenafil, a Selective Phosphodiesterase 5 Inhibitor, in Patients with Erectile Dysfunction and Arterial Hypertension Treated with Multiple Antihypertensives

Recent analyses suggest that about 67-68% of men with hypertension have some degree of erectile dysfunction (ED). With about 25 million men in the US with hypertension, substantial numbers of hypertension-related ED exist that tend to be of a more severe nature than the general population. Men with ED are also more likely to have hypertension. Thiazide diuretic and beta-blocker therapy may contribute to ED. Phosphodiesterase-5 (PDE5) inhibitors are effective therapy in men with ED owing to hypertension who are taking antihypertensive medicines including those on multiple antihypertensive medicines. The addition of PDE5 inhibitors to usual common antihypertensive medicines (diuretics, beta blockers, calcium blockers, angiotensin converting enzyme inhibitors and angiotensin receptor blockers) results in either no or small additive reductions in blood pressure (BP) and no increase in serious clinical adverse events. There are however precautions regarding the use of PDE5 inhibitors in patients taking alpha blockers for either hypertension or benign prostatic hypertrophy, as some patients may develop orthostatic hypotension. Organic nitrates remain an absolute contraindication for PDE5 inhibitors because synergistic and symptomatic reductions in BP may occur in some patients with this drug combination.

Section: Does the Addition Of Pde5 Inhibitors To Antihypertensive Agementioning

confidence: 99%

Section: The Association Of Hypertension With Edmentioning

confidence: 99%

Erectile dysfunction and hypertension

Kloner

2006

“…A value of 19.47 for Cochran's Q 3 was reported with an associated value of 33.23% (assuming 13 degrees of freedom) for Higgins' I. 2,4 Although the test failed to reject the null hypothesis of homogeneity, it has been noted that this test lacks adequate power. 5 As a result, investigators often use a ¼ 0.10 as a threshold for statistical significance when performing the Q-test.…”

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confidence: 99%

“…For example, a recent study in PDE5-inhibitor-naïve men with ED and hypertension showed average EF domain score improvements with vardenafil of 10.7 points from baseline. 2 The authors acknowledge that 'in cases of insufficient data, standard deviations (SD) were substituted. The estimation was based either on figures presenting confidence intervals (CIs), standard errors, or SDs or on other studies with the same agent, which reported SD for treatment and placebo group.'…”

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confidence: 99%

Efficacy of PDE-5-inhibitors for erectile dysfunction. A comparative meta-analysis of fixed-dose regimen randomized controlled trials administering the International Index of Erectile Function in broad-spectrum populations

Rosen

Shaw

2006

We read with interest the meta-analysis of fixeddose studies on the efficacy of PDE5 inhibitors by Berner and colleagues (Int J Impot Res 2006; 18: 229-235). The authors suggested superiority of sildenafil compared to vardenafil based on relative improvements in IIEF-EF domain scores. 1 However, their analysis fails to consider the following issues.The studies had different durations of treatment. Although the modal duration was 12 weeks, three of the studies were for 3, 4 and 8 weeks and one at 26 weeks. These differences in study duration could have influenced outcomes in several ways, including increased discontinuation rates or disease progression in the longer duration studies.The sildenafil studies were conducted, on average, about 3 years earlier than the tadalafil and vardenafil studies. As a result, the patients were PDE5-inhibitor-naïve, which may have made them more responsive to treatment. For example, a recent study in PDE5-inhibitor-naïve men with ED and hypertension showed average EF domain score improvements with vardenafil of 10.7 points from baseline. 2 The authors acknowledge that 'in cases of insufficient data, standard deviations (SD) were substituted. The estimation was based either on figures presenting confidence intervals (CIs), standard errors, or SDs or on other studies with the same agent, which reported SD for treatment and placebo group.' Imputing data broadly in this manner could result in a significant degree of bias in the comparison.Several tests of heterogeneity were performed. A value of 19.47 for Cochran's Q 3 was reported with an associated value of 33.23% (assuming 13 degrees of freedom) for Higgins' I. 2,4 Although the test failed to reject the null hypothesis of homogeneity, it has been noted that this test lacks adequate power. 5 As a result, investigators often use a ¼ 0.10 as a threshold for statistical significance when performing the Q-test. At this level, the authors' test result raises questions about the appropriateness of pooling the studies. The funnel plot also suggests the presence of a moderate degree of heterogeneity across studies.A related statistical concern is their selection of a fixed effects model (FEM) for the meta-analysis. The FEM assumes that variability in the study results is exclusively the result of random variation. 6 In contrast, a random effects model (REM) 7 assumes different underlying sources of variance for each study and considers this as a potential source of variation in the model. When there is substantial between-study variation, REM will tend to yield larger CIs than FEM. If an REM model had been used, it is conceivable that observed differences among the agents would not have been statistically significant. The authors should ideally have tested both models and, in the event that different results were obtained, reported both sets of findings. This is commonly performed in meta-analyses published in top-tier journals. 8,9 The IIEF-EF domain score can be assessed in one of three ways: (1) absolute values at baseline and end point...

“…39 In subjects with ED and hypertension, vardenafil did not alter the blood pressure of subjects taking antihypertensives. 40 In healthy subjects, tadalafil caused very small changes in blood pressure that were not considered to be clinically relevant. 38 Tadalafil reduced mean standing blood pressure by À4.6 mm Hg in patients with hypertension, but this unlikely to be of major concern.…”

Section: Vardenafil and Tadalafil Have Advantages Over Sildenafil S Dmentioning

confidence: 99%

Do vardenafil and tadalafil have advantages over sildenafil in the treatment of erectile dysfunction?

Doggrell

2006

Erectile dysfunction (ED) affects up to 50% of men between the ages of 40 and 70 years of age. Sildenafil, vardenafil and tadalafil have all been shown to be similarly effective in the treatment of men with ED of vary etiologies, to have similar adverse effects profiles, and to improve quality-oflife by similar amounts. As these phosphodiesterase 5 (PDE5) inhibitors all increase the hypotensive effects of nitrates, they are not suitable for use in patients taking nitrates for the treatment of ischaemic heart disease. All three inhibitors must be used with caution in patients taking a 1 -adrenoceptors antagonists for benign prostatic hyperplasia. Although nonarteritic anterior ischaemic neuropathy has been reported in some users of the PDE5 inhibitors, there is no conclusive evidence that PDE5 inhibitors cause this rare effect. Tadalafil has a longer half-life than sildenafil or vardenafil, and a longer duration of action than sildenafil and vardenafil. Most preference studies have shown tadalafil to be preferred, but there are serious limitations to some of these studies. One approach to treatment is to give each patient a short-and long-acting agent, and for individuals to decide their preference.