539Vardenafil improves erection quality assessed by the novel erection quality scale in the broad population of men with erectile dysfunction

537

538

HAEMO-

INFLUENCE OF SPINAL CORD INJURY SEVERITY ON EJACULATORY FUNCTION, ERECTILE FUNCTION AND TOLERABILITY OF VARDENAFIL IN MEN WITH ERECTILE DYSFUNCTION CONSEQUENT TO TRAUMATIC SPINAL CORD INJURY

lH6pital Kremlin-Bic~tre, Urology, Le Kremlin-Bic~tre, France, 2Columbia Presbyterian Medical Center, Urology, New York, United States, 3SanofiSynthelabo Recherche, Urology, Montpellier, France, 4Biotrial, Urology, Rennes, France

Giuliano F.1, Rubio-Aurioles E.2, Kennelly M.3, Montorsi E 4, Kim E.D.~, Finkbeiner A.6, Colopy M.7, Wilkins H.J.8, Wachs B2, Vardenafil Study Group

TADALAFIL SHOWS NO CLINICALLY SIGNIFICANT DYNAMIC INTERACTION WITH ALFUZOSIN Giuliano F. t , Kaplan S. z, Fourni6 p.3, Cabanis M.J. 3, Astruc B. 4

INTRODUCTION & OBJECTIVES: The link between lower urinary tract symptoms (LUTS) and sexual dysfunction including erectile dysfunction (ED) and ejaculatory disorders has been recently evidenced in various epidemiological studies. The co-prescription of drugs treating LUTS and ED is increasing. Both .phosphodiesterase 5 inhibitors and alpha-blockers are safe but they may have an impact on blood pressure which differs from one drug to another in a same class. We evaluated the hemodynamic interactions of tadalafil with the clinically uroselective al-blocker, alfuzosin. MATERIAL & METHODS: In a double-blind, randomized crossover study, we examined the effect of tadalafil 20mg or placebo in combination with alfuzosin 10mg once daily (OD). Healthy volunteers received alfuzosin 10 mg (n=18) daily for 7 days. Tadalafil 20rag or placebo was given 4 hours after the last dose of alfuzosin 10mg. Blood pressure (BP) was recorded pro-dose and for 24 hours postdose. RESULTS: In subjects on alfuzosin 10 mg, tadalafil 20 mg produced mean maximal decreases in standing systolic and diastolic BP that were only 4.3 mmHg and 3.5 mmHg greater than placebo, respectively (95% confidence intervals (-8.9; 0.4) and (-5.4; -1.6) respectively). The mean maximal decrease in supine systolic and diastolic BP were only -2.1 mmHg and -0.9 mmHg respectively (95% confidence intervals (-5.25; 0.9) and (-3.1; 1.3)) respectively. Analysis of outliers on alfuzosin 10 mg showed that the number of potentially clinically important BP effects was low and was similar between tadalafil 20 mg and placebo. Moreover, no subjects taking alfuzosin 10 mg plus tadalafil 20 mg or placebo dropped their standing systolic BP >30mmHg or diastolic BP >20mmHg from baseline. CONCLUSIONS: Tadalafi120 mg shows no clinically significant haemodynamic interaction with alfuzosin 10rag OD. Because alfuzosin 10 mg is not responsible for any deleterious effect on sexual function including erection and ejaculation, and is well tolerated in association with tadalafil 20 mg, it might be considered as the treatment of choice for BPH patients complaining about ED and receiving tadalafil.

tCHU de Bicetre, Urology, Le Kremlin Bicatre Codex, France, ?Private Practice, Private Practice, Deleg, Tlalpan, Mexico, 3CarolinasMedical Center, Urology, Charlotte, United States, 4Universita' Vita Salute San Raflhele, Urology, Milan, Italy, 5Ut Medical Center at Knoxville, Volunteer Research Group, Inc., Knoxville, United States, 6Universityof Arkansas, Medical Science, Little Rock, United States, 7GlaxoSmithKline,Biostatistics,Research Triangle park, United States, 8GlaxoSmithKline,Migu - Medicine Development Denier, King Of Prussia, United States, 9Atlanta Urology Medical Group, Urology,Long Beach, United States INTRODUCTION & OBJECTIVES: To determine the influence of the severity of spinal cord injury (SCI) on erectile

function, ejaeulatory function and tolerability of vardenafil in men with ED due to a traumatic SCh

MATERIAL & METHODS: In this multicenter, double-blind, parallel group 12-week study, 418 patients >18 years of age with ED >6 months consequent to SCI were randomized to vardenafil 10rag (n-207) or placebo (n-211) for 4 weeks, with option to remain on vardenafil 10mg or titrate to 5mg/20rag at weeks 4 and 8. Efficacy variables included the IIEF-EF domain score, mean per patient positive responses to diary questions regarding vaginal penetration (SEP2), maintenance of erection to completion of intercourse (SEP-3), and the Global Assessment Question (GAQ) regarding erection improvement over the past four weeks. Ability to ejaculate, based on diary responses, was also assessed. Efficacy parameters were stratified by severity of SCI as defined by ASIA (Category A - no sensory/motor function preserved in sacral segments; Category B-D - partial sensory/motor funation preserved). RESULTS: Mean baseline EF domain scores were 11.6 /12.l (moderate ED) in the vardenafil /placebo groups,

respectively. Overall, approximately half of all subjects in each treatment group had Category A SCI while the remainder had Category B-D SCh Vardenafil clinically and statistically improved alI key efficacy parameters vs. Jlacebo irrespective of SCI ASIA class.

IIEF-EF domain (LS mean score, BL/LOCF) IIEF-EF >26 (% of patients, BL/LOCF)

ASIA Category A Placebo Vardenafil (n-96-100) (n=94-96) 12.2/12.7 11.5/21.3'

ASIA Category B-D Placebo Vardenafil (n=96-98) (n-101) 12.6/14.5 12.7/22.1'

2%/1 I%

0%/7%

2%/55%*

3 8 . 3 % / 3 7 . 1 % 36.4%/73.2%*

47.l%/44.0%

41.0%/74.4%*

1 3 . 1 % / 1 8 . 6 % ll.9%/55.2%*

7.9%/25.1%

I0.1%/60.6%*

26% 5.1%/4.0%

27% 22.1%/14.9%

77%* 19.0%/28.7%*

SEP-2(LSmeanperpatient

success rate, BL/overall) SEP-3 (LS mean per patient successrate, BL/overall) GAQ (% of patients -yes, LOCF) Ejaculation (LSmean per patient success rate, BL/overall)

1%/47%*

83%* 3.7%/8.0%

Analyses were ad hoc, *-nominal p<0.05. The most fi'equentlyreported adverse events (AEs) included headache (16%/5%), UTI (1 I%/10%), flushing (6%/0%), nasal congestion (5%/0%), diarrhea (3%/4%), and dyspepsia (4%/0%) in patients receiving vardenaffi/placebo, respectively. Serious AEs occurred in 2%/3% of patients receiving vardenafil/plaeebo, respectively; none were considered to be treatmezlt-related. CONCLUSIONS: In men with ED due to traumatic SCI, flexible dose vardenafll clinically and statistically improved all key efficacy parmneters vs. placebo irrespective of SCI ASIA class. These fndings have important implications for

QoL and fertility in patients with SCI.

539

540

VARDENAFIL IMPROVES ERECTION QUALITY ASSESSED BY THE NOVEL ERECTION QUALITY SCALE IN THE BROAD POPULATION OF MEN WITH ERECTILE DYSFUNCTION

CARDIOVASCULAR SAFETY OF VIAGRA®: RESULTS OF THE INTERNATIONAL MEN'S HEALTH STUDY Giuliano I;, I, Porst H. 2, Hedelin H. 3, Martin-Morales A. 4, Sobel R. 5, Reynolds R. 5, Glasser D. s

Rosen R?, Fisher W.2, Brock G), Karlin G.4, Pommerville p.5, Huaag X.Y.6, Bangerter K. 7, Bandel T.8, Derogatis L. 9, Vardenafil Study Group IUMDNJ-Robert Wood Johnson Medical School, Psychiatry, Piscataway, United States, 2University of Western Ontario, Psychology and Obstetrics and Gynaecology, London, Ontario, Canada, 3St Joseph's Medical Center, Lawson Research Institute, London, Ontario, Canada, 4Lawrenceville Urology, Practice, Lawrenceville, United States, SVictoria General Hospital, Urology, Victoria, Canada, 6Bayer Healthcare Pharmaceuticals, Global Health Economics & Outcomes Research, West Haven, United States, 7Bayer Healthcare Pharmaceuticals, Biometry, West Haven, United States, 8Bayer Healthcare AG, Medical Affairs, Elberfeld, Germany, 9University of Maryland, School of Nursing, Baltimore, United States INTRODUC]FION & OBJECTIVES: Although numerous instruments are available to measure erectile

function, not until recently has there been an instrument that measures the qualitative aspects of penile erections, attributes important to both patients and their partners. The Erection Quality Scale (EQS) has recently been developed and validated. Here the influence of vardenafil (VAR) on erection quality was assessed. MATERIAL & METHODS: In a double-blind, multicenter, 12-week randomized trial, 229 men with ED received placebo (PLA) or VAR 10 nag for 4 weeks, with option to stay on 10 nag, or titrate to 5 mg or 20 mg aider each of two consecutive, 4-week intervals. Female partners (N=229) of these ED males, age >18 years without sexual dysfunction were also enrolled. The prinaary efficacy variables were the mean/patient saccess rate of maintenance erection maintenance (SEP-3), and improvement of partner's sexual quality of life (measured as quality of life domain of parmers' modified Sexual Life Quality Questionnaire (roSLQQ-QoL). Additional secondary efficacy variables included responses to the EQS. Differences between groups in the ITT population were determined by ANCOVA. RESULTS: Mean baseline EF domain of the ITT population (112 PLA and 113 VAR patients) was 13.2-13.5

(moderate ED). VAR significantly improved overall LS mean/patient SEP-3 success rates (67.7% [BL, 19.8%]) versus PEA (27.8% [baseline, 21.2%], p<0.0001), and the partner mSLQQ-QoL (65.8 [BL 27,7] vs. 32.1 [BL 25.9] p<0.0001, LOCF). Vardenafil significantly improved all EQS variables in statistically (p<0.0001) and clinically significant manner relative to PLA at LOCI;, including EQS total score (36.I vs. 14.6); and individual questions - ease in ability to get erection (2.4 vs. 0.9); how often to get an erection quickly and easily (2.6 vs. 1.1); confidence in ability to get an erection (2.3 vs. 1.0); how satisfied in ability to get an erection (2.4 vs. 0.7); how often did erections last long enough for penetration (2.8 vs. 1.4); how often did erections last long enough for ejaculation (2.7 vs. 1.3); confidence in ability to keep an erection once you got one (2.3 vs. 0.7); how satisfied you were in amount of time erections lasted (2.2 vs. 0.4); hardness of erection (2.4 vs. 1.1); how often were erections hard enough for penetration (2.8 vs. 1.3); how satisfied you have been with erection hardness (2.2 vs. 0.5); amount of pleasurable feeling in erect penis (2.5 vs, 1.4); satisfaction with pleasurable feeling in penis during sex (2.6 vs. 1.6); frequency worrying about erections when attempting sex (1.9 vs. 0.8); how satisfied were you with overall quality of erection (2.2 vs. 0.4), VAR was generally well-tolerated. The roost frequently reported adverse events (<1!%) included flushing, nasal congestion, headache, and dyspepsia. CONCLUSIONS: In this study, VAR significantly improved perceived erection quality on all measures of the

EQS commensurate with improvements in completion of sexual intercourse and improved partner sexual QoL.

IHopital de Bicetre, Depam~lent of Urology CHU de Bicetre, Le Cremilin Bicetre, France, ZPrivate Urological Practice, Private Urological Practice, Hamburg, Germany, 3Department of Urology Skaraborgs Sjukhus, Urology, Sk6vde, Sweden, 4Hospital Egiunal Universitario Carlos Haya, Urology, Malaga, Spain, sPfizer Inc., Pfizer Inc., New York, United States I N T R O D U C T I O N & O B J E C T I V E S : To estimate the rates o f acute cardiovascular disease (CVD)

events in men with erectile dysfunction (ED) who seek and receive treatment with Viagra. M A T E R I A L & M E T H O D S t Patients were recruited from the community by general practitioners

and urologists in France, Germany, Spain, and Sweden. Included men had scores <21 on the Erectile Function domain (range, 0-30) of the International Index o f Erectile Function and had been prescribed Viagra. Patients completed a baseline questionnaire with items related to medical history, health status, medications, and risk factors for CVD. A follow-up questionnaire was mailed to patients quarterly, and they were asked to update baseline information, as well as provide data related to frequency o f sexual activity and use of Viagra or other ED treatments. Post-event questionnaires (PEQ) were completed by patients after possible nonfatal myocardial infarction (MI) or cerebrovascular accident. This questionnaire assessed frequency and timing of exposure to Viagra or other ED treatments, as well as sexual activity shortly before event onset. Hospitalizations for CVD events, per 100 person-years (PY), were stratified by age, CVD risk factors, and exposure to Viagra. RESULTS: Enrolment by country is summarized in the Table. The mean age (±SD) of the intent-totreat population (n=3813) was 57±11 years. The most prevalent risk factors for CVD were frequent alcohol use (45%), hypertension (36%), high cholesterol (26%), and smoking (25%). Patients with 0, I, 2, and >2 risk factors for CVD comprised 5%, 25%, 30%, and 40% of patients, respectively. Incidence of all-cause mortality was 0.4 per 100 PY. MI and stroke incidences were 0.7 and 0. I per 100 PY, respectively. MI occurred with approximately twice the frequency in patients aged >55 y as in those <55 y. Incidence o f MI increased 3-fold in patients with >2 CVD risk factors compared with those with only 1. Of the 30 patients who had a CVD event, 21 completed a PEQ. Of these, only 29% had received ED treatment in the month belbre hospitalization. For those reporting Viagra use, the mean time elapsed between Viagra use and onset of CVD event symptoms was 6 days, well beyond 6 half-lives (24 h). C O N C L U S I O N S : Incidence o f CVD events for men prescribed Viagra in this community-based

study was low and comparable to previously published figures from clinical trial and epidemiologic data. Age, ED severity, and CVD risk factors were positively associated with incidence o f CVD events. There is no evidence to suggest that Viagra use is associated with an increased risk of CVD. Table 1 : Enrolment Summary France

Germany

Spain

] Sweden

First Enrolment Date

Jan-02

Aug-01

Dec-02

' Aug-03

Total

Physicians Enrolling >I Patient

112

247

189

14

562

Baseline Questionnaires Received

614

3041

970

452

5077

Analyzable Population

487

2591

343

392

3813

European Urology Supplements 4 (2005) No. 3, pp. 137