Effects of tadalafil once daily or on demand versus placebo on time to recovery of erectile function in patients after bilateral nerve-sparing radical prostatectomy.

PURPOSE: We report time to erectile function (EF)-recovery data from a multicenter, randomized, double-blind, double-dummy, placebo-controlled trial evaluating tadalafil started after bilateral nerve-sparing radical prostatectomy (nsRP). METHODS: Patients ≤68 years were randomized post-nsRP 1:1:1 to 9-month double-blind treatment (DBT) with tadalafil 5 mg once daily (OaD), 20 mg tadalafil on demand ("pro-re-nata"; PRN), or placebo, followed by 6-week drug-free washout (DFW) and 3-month open-label OaD treatment. Secondary outcome measures included Kaplan-Meier estimates of time to EF-recovery (IIEF-EF ≥ 22) during DBT (Cox proportional hazard model adjusting for treatment, age, and country). RESULTS: A total of 423 patients were randomized to tadalafil OaD (N = 139), PRN (N = 143), and placebo (N = 141); 114/122/155 completed DBT. The proportion of patients achieving IIEF-EF ≥22 at some point during DBT with OaD, PRN, and placebo was 29.5, 23.9, and 18.4 %, respectively. DBT was too short to achieve EF-recovery (IIEF-EF ≥ 22) in >50 % of patients; median time to EF-recovery was non-estimable. Time for 25 % of patients to achieve EF-recovery (95 % CI) was 5.8 (4.9, 9.2) months for OaD versus 9.0 (5.5, 9.2) and 9.3 (9.0, 9.9) months for PRN and placebo, respectively. Showing a significant overall treatment effect (p = 0.038), the probability for EF-recovery was significantly higher for OaD versus placebo [hazard ratio (HR); 95 % CI 1.9; 1.2, 3.1; p = 0.011], but not for PRN versus placebo (p = 0.140). Of 57 OaD patients (41.0 %) with ED improved (by ≥1 IIEF-EF severity grade) at the end of DBT, 16 (28.1 % of 57) maintained this improvement through DFW and 27 (47.4 %) declined but maintained improvement from baseline after DFW. CONCLUSIONS: Data suggest that the use of tadalafil OaD can significantly shorten the time to EF-recovery post-nsRP compared with placebo.

Evaluating a continuous medical education program to improve general practitioners awareness and practice on erectile dysfunction as a cardiovascular risk factor.

INTRODUCTION: The clear link between erectile dysfunction (ED) and cardiovascular disease (CVD) together with the increased potential for effectively treating ED with oral pharmacological agents make the primary care setting the ideal place to detect and treat ED and its potential comorbidities. Given the observed shortcomings in knowledge related to ED among primary care physicians, continuous medical education (CME) on this topic stands out as a potentially effective way to improve patient care. AIM: To assess general practitioners' (GPs) knowledge, attitudes, and self-confidence about ED management and the relationship between ED and CVD and to test whether these can be improved by means of a brief training program. METHODS: Eighty GPs completed two similar questionnaires on ED issues, one prior to a CME intervention and one following it. The CME program consisted of reading an annotated set of four review articles and six research articles followed by a live half-day seminar conducted by a GP, a urologist, and a cardiologist. MAIN OUTCOME MEASURES: Changes in the answers to the two questionnaires were evaluated by tests for matched pairs using both statistical significance and effect size estimates, and assessment of different predictors were evaluated by multivariate analysis. RESULTS: A marked improvement was observed in physician knowledge, attitudes, and self-confidence with regard to diagnosing and treating ED following the CME training intervention. CONCLUSIONS: The present study shows that a relatively simple educational procedure can substantially improve the awareness of primary care physicians about the cardiovascular implications of ED and their self confidence in the management of these patients.

Raloxifene is not associated with biologically relevant changes in hot flushes in postmenopausal women for whom therapy is appropriate.

OBJECTIVES: Raloxifene is approved for the treatment and prevention of postmenopausal osteoporosis. Previous studies have described a raloxifene-associated increase in hot flushes, reported as adverse events. This study was undertaken to provide a detailed evaluation of the potential of raloxifene to induce or exacerbate hot flushes in postmenopausal women. STUDY DESIGN: In this double-blind, placebo-controlled, parallel group multicenter study, 487 postmenopausal women were randomized to receive 8 months of treatment with either raloxifene (RLX) at the recommended dose of 60 mg/day, or by slow-dose escalation for the first 2 months, followed by the standard dose for the rest of the study (SDE), or placebo (PL). The frequency, duration, intensity, severity, and impact of hot flushes were measured. RESULTS: With 3-5 hot flushes per week, the mean number at baseline was low. During treatment, it increased by <1 hot flush/week in both active treatment groups and decreased by <1 hot flush/week with PL. The high proportion ( approximately 60%) of asymptomatic patients at baseline had increased further by the end of treatment in all groups. The proportion of women whose pre-existing hot flushes abated during treatment was significantly greater with SDE (P=.005) and PL (P=.050), but not with RLX, when compared with the proportion with treatment-emergent flushes. There were no statistically significant between-group differences in the distribution of the number of hot flushes after 2 months of treatment. At end point, there were no significant differences between SDE and either RLX or PL, but the difference between RLX and PL was statistically significant (P=.035). There were no significant between-group differences in the hot flush impact scores, in treatment satisfaction, and in the proportion of patients requesting symptomatic treatment to alleviate hot flushes. CONCLUSION: In a postmenopausal population meeting the criteria for the prescription of RLX, the overall effect of the drug on hot flushes is low. Previous studies using adverse event reports have overestimated the importance of hot flushes in postmenopausal women during treatment with RLX. Slow-dose escalation seems to decrease the number of symptomatic patients further and may be a useful strategy in women reporting flushes when starting RLX.

Compliance and satisfaction with raloxifene versus alendronate for the treatment of postmenopausal osteoporosis in clinical practice: An open-label, prospective, nonrandomized, observational study.

BACKGROUND: The treatment of osteoporosis among postmenopausal women represents a major public health challenge because long-term therapy is needed to prevent fractures and chronic disability. Low patient compliance with prescribed osteoporosis treatments can severely distort the validity of controlled clinical trials. Raloxifene and alendronate have been shown to reduce the incidence of osteoporotic fracture in postmenopausal women in well-conducted randomized trials, but few data are available on the rate of adherence to these treatments in routine clinical practice. OBJECTIVE: The primary aim of this study was to assess the compliance of postmenopausal women at risk for osteoporotic fractures who were treated with raloxifene hydrochloride (RLX) versus alendronate sodium (ALN) during a 12-month observational period in a routine clinical setting. Secondary objectives were the assessment of factors that might contribute to noncompliance and patient satisfaction. METHODS: This open-label, prospective, multicenter, nonrandomized, observational, comparative study was conducted at 154 centers across Spain. Assignment to either RLX or ALN treatment was determined by the physician and was based on each patient's clinical profile. Compliance with RLX (60-mg tablet once daily) versus ALN (10-mg tablet once daily) was assessed using 3 different compliance assessment tools: the Morisky-Green test, the Autocompliance test, and the Compliance Questionnaire. A logistic regression model was used to assess different factors affecting compliance. Patient satisfaction was also assessed using a questionnaire. Adverse events (AEs) were collected as reasons for discontinuation in the Compliance Questionnaire and at the discontinuation visit. RESULTS: A total of 902 women (RLX group, n = 476; ALN group, n = 426) were included in the study (mean age, 64.4 [6.9] years). Overall, patients in the RLX group reported significantly better compliance than patients in the ALN group, as collected either by the Morisky-Green test (68.7% vs 54.0%; P < 0.001) or the Autocompliance test (94.7% vs 90.6%; P = 0.033). More patients discontinued treatment prematurely in the ALN group compared with the RLX group (25.8% vs 16.4%; P < 0.001). The age-adjusted relative risk for discontinuation was 1.4-fold higher for women treated with ALN than for those treated with RLX (95% CI, 1.21-1.61). The main reason for premature discontinuation was due to AEs (RLX 4.8% vs ALN 11.0%; P < 0.001). The proportion of patients with gastrointestinal AEs was 9.9% in the ALN group and 3.4% in the RLX group (P < 0.001). Only treatment and type of physician were independent covariates of treatment compliance. After 12 months of observation, significantly more patient in the RLX group were satisfied or very satisfied with their treatment than patients in the ALN group (P < 0.001). CONCLUSION: In this study of postmenopausal women at risk for osteoporotic fractures, compliance with 12-month treatment with daily RLX was higher than with daily ALN in clinical setting. RLX showed significant benefits compared with ALN in terms of compliance assessed by means of the Morisky-Green and Autocompliance tests and the patients' self-reported satisfaction.