ramipril and Erectile-Dysfunction

Although erectile dysfunction (ED) is associated with cardiovascular risk factors and atherosclerosis, it is not known whether the presence of ED is predictive of future events in individuals with cardiovascular disease. We evaluated whether ED is predictive of mortality and cardiovascular outcomes, and because inhibition of the renin-angiotensin system in high-risk patients reduces cardiovascular events, we also tested the effects on ED of randomized treatments with telmisartan, ramipril, and the combination of the 2 drugs (ONTARGET), as well as with telmisartan or placebo in patients who were intolerant of angiotensin-converting enzyme inhibitors (TRANSCEND).. In a prespecified substudy, 1549 patients underwent double-blind randomization, with 400 participants assigned to receive ramipril, 395 telmisartan, and 381 the combination thereof (ONTARGET), as well as 171 participants assigned to receive telmisartan and 202 placebo (TRANSCEND). ED was evaluated at baseline, at 2-year follow-up, and at the penultimate visit before closeout. ED was predictive of all-cause death (hazard ratio [HR] 1.84, 95% confidence interval [CI] 1.21 to 2.81, P=0.005) and the composite primary outcome (HR 1.42, 95% CI 1.04 to 1.94, P=0.029), which consisted of cardiovascular death (HR 1.93, 95% CI 1.13 to 3.29, P=0.016), myocardial infarction (HR 2.02, 95% CI 1.13 to 3.58, P=0.017), hospitalization for heart failure (HR 1.2, 95% CI 0.64 to 2.26, P=0.563), and stroke (HR 1.1, 95% CI 0.64 to 1.9, P=0.742). The study medications did not influence the course or development of ED.. ED is a potent predictor of all-cause death and the composite of cardiovascular death, myocardial infarction, stroke, and heart failure in men with cardiovascular disease. Trial treatment did not significantly improve or worsen ED.. URL: http://www.clinicaltrials.gov. Unique identifier: NCT 00153101.

Topics: Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Benzimidazoles; Benzoates; Cardiovascular Diseases; Double-Blind Method; Drug Therapy, Combination; Erectile Dysfunction; Humans; Male; Mortality; Predictive Value of Tests; Ramipril; Telmisartan; Treatment Outcome

Erectile dysfunction (ED) is a common disorder in middle-aged men and is significantly influenced by cardiovascular risk factors (CVRFs) and cardiovascular disease. The substudy of the ONTARGET/TRANSCEND trials evaluates the relationship of erectile function to baseline characteristics and current treatment in cardiovascular high-risk patients who have been enrolled in these trials. The effects of treatment with telmisartan and ramipril, alone or in combination, including a telmisartan versus placebo arm will be determined prospectively during a follow-up of 4 years.. One thousand three hundred fifty-seven patients were evaluated in 13 countries at baseline, 2 years, and 4 years, with ED determined using the ED score of the Cologne Male Survey (Kölner [Cologne] Evaluation of Erectile Dysfunction) and the 5-item International Index of Erectile Function. Erectile dysfunction scores were related to CVRF and the use of cardiovascular drugs.. Prevalence of ED was 50.7% (Kölner [Cologne] Evaluation of Erectile Dysfunction) and 54.3% (5-item International Index of Erectile Function), respectively, with a decline of sexual activity after the diagnosis of cardiovascular disease. In multivariate analysis, diabetes mellitus (P < .00001), stroke (P = .00026), pelvic surgery (P = .025), and age of >65 years (P < .00001) correlated with the degree of ED. No significant associations were observed for cholesterol levels, hypertension, and smoking status as well as current treatment with angiotensin-converting enzyme inhibitors, angiotensin I antagonists, diuretics, beta-blockers, or calcium-channel blockers.. The ONTARGET/TRANSCEND-ED substudy shows a significant influence of cardiovascular disease on erectile function. In contrast to prior smaller studies, drug therapy and CVRF seem to play a minor role in cardiovascular high-risk patients. Follow-up data will provide information whether angiotensin-converting enzyme inhibitors, angiotensin I antagonists, or a combination thereof are able to improve erectile function.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Benzimidazoles; Benzoates; Cardiovascular Diseases; Drug Therapy, Combination; Erectile Dysfunction; Global Health; Humans; Male; Middle Aged; Multivariate Analysis; Patient Satisfaction; Prospective Studies; Ramipril; Risk Factors; Telmisartan

Erectile dysfunction correlates with cardiovascular disease and its common risk factors due to the development of endothelial dysfunction. Positive effects on endothelial and erectile function have been described for substances inhibiting the renin-angiotensin-system. Here, we investigated in an atherosclerosis model, whether telmisartan (angiotensin receptor blocker) and ramipril (angiotensin converting enzyme inhibitor) are equivalent or the combination of both is superior in improving endothelial function in the aorta and the corpus cavernosum and in reducing atherosclerosis.. Wild-type (WT, C57/B6) and apolipoprotein-E-deficient (ApoE(-/-) ) mice were treated with a cholesterol-rich diet for 8 weeks. ApoE(-/-) mice were supplemented with either telmisartan (20 mg·kg(-1) ·day(-1) ), ramipril (2.5 mg·kg(-1) ·day(-1) ) or the combination thereof.. Systolic blood pressure significantly decreased in treatment groups (P < 0.001), with significantly smaller reduction under ramipril monotherapy (P < 0.05). Endothelial function (assessed by pharmacological stimulation of aortic rings and corpus cavernosum in organ bath chambers) was impaired in ApoE(-/-) mice compared to WT animals, which was improved by all three treatments to a comparable extent (P < 0.05). Atherosclerotic lesion size in the ascending aorta and aortic sinus (P < 0.001), the amount of lipid peroxides in cavernosal and aortic tissue (P < 0.05) and free radical load (dihydroethidium-stain) (P < 0.05) were enhanced in untreated ApoE(-/-) mice in comparison to WT animals and were significantly reduced by either treatment. In penile tissue, expression of eNOS could be restored by renin-angiotensin-aldosterone system blockade.. Telmisartan and ramipril significantly improved endothelial function of aortic and cavernosal tissues in ApoE(-/-) via reduction of oxidative stress. Combination of both agents does not enhance beneficial effects significantly.

Topics: Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Animals; Aorta; Atherosclerosis; Benzimidazoles; Benzoates; Blood Pressure; Cholesterol; Drug Therapy, Combination; Endothelium, Vascular; Erectile Dysfunction; Free Radicals; Lipid Peroxides; Male; Mice; Mice, Inbred C57BL; Nitric Oxide Synthase Type III; Ramipril; Renin-Angiotensin System; Telmisartan