Transcript Slide 1
Learning Objectives
• • • • •
Accurately recognize overactive bladder (OAB), with urgency as the core symptom, in the context of other urinary symptoms that are commonly encountered in men and women Confidently assess important measures like symptom severity and health-related quality of life (HRQOL) and use this information for patient management Apply behavioral and lifestyle modifications to treatment strategies using an individualized and patient-centered approach to OAB Understand the current first-line treatments for OAB in both men and women Employ a patient-centered treatment strategy that explores the benefits of dosing antimuscarinics to obtain a balance between efficacy and tolerability
Premeeting Survey
•
True or False: The core symptom of OAB is urgency.
1. True 2. False
?
Premeeting Survey
•
Which of the following are NOT considered comorbidities in patients with OAB?
1.
2.
3.
4.
Falls and fractures Urinary tract infections (UTIs) Skin infections Kidney stones
?
Premeeting Survey
•
True or False: Using a flexible-dosing regimen of antimuscarinics results in improved efficacy and patient satisfaction.
1. True 2. False
?
Overactive Bladder: Impact
Matt T. Rosenberg, MD MidMichigan Health Centers Jackson, MI
ICS Definition of Overactive Bladder
• • •
A symptom syndrome suggestive of lower urinary tract dysfunction 1,2 Urgency, with or without urge incontinence, usually with frequency and nocturia 1,2 In absence of metabolic or pathologic conditions 1,2 ICS: International Continence Society 1 Abrams P, et al. Neurourol Urodyn. 2002;21:167-178.
2 Wein AJ, et al. Urology. 2002;60(5 suppl 1):7-12.
Overactive Bladder Definitions
Urgency Frequency Nocturia 1,2 1,2 1,2 Sudden compelling desire to pass urine that is difficult to defer Patient considers that he/she voids too often by day Normal is < 8 times per 24 hours Waking to urinate during sleep hours Considered a clinical problem if frequency is greater than twice a night Urge urinary incontinence (UUI) 1 OAB “wet” 1,2 OAB “dry” 2 Warning time 3 Involuntary leakage accompanied by or immediately preceded by urgency OAB with UUI OAB without UUI Time from first sensation of urgency to voiding 1 Abrams P, et al. Neurourol Urodyn. 2002;21:167-178.
2 Wein AJ, et al. J Urol. 2006;175(3 pt 2):S5-S10.
3 Zinner N, et al. Int J Clin Pract. 2006;60:119-126.
Healthy Bladder Versus Overactive Bladder
• • • •
Holds 300-500 cc Empties < 8 times per day Holds at night After gradual filling, urge is felt
• • •
Empties > 8 times per day Empties > 2 times per night Has urgency (sudden compelling desire to void that is difficult to defer) Pfisterer MH-D, et al. Neurourol Urodyn. 2007;26:356-361.
Wein AJ. Am J Manag Care. 2000;6(11 suppl):S559-S564.
Wein AJ, et al. J Urol. 2006;175(3 pt 2):S5-S10.
OAB Symptoms Are as Prevalent in Men as in Women and Increase With Age
40 35 30 25 Population-based prevalence studies
:
Comparison of data from the SIFO study (1997)* 1 and the EPIC study (2005) †2
Men (SIFO 1997) Women (SIFO 1997) Men (EPIC 2005) Women ( EPIC 2005) 16.6
11.8
20 15 10 5 0 18-29 30-34 35-39 40-44 45-49 50-54 55-59 60-64 65-69 Age (years) SIFO: Sifo/Gallup telephone survey * N = 16,776 interviews (6 European countries) † N = 19,165 interviews (4 European countries and Canada) > 70 1 Milsom I, et al. BJU Int. 2001;87:760-766.
2 Irwin DE, et al. Eur Urol. 2006;50:1306-1314.
Urgency Leading to Urgency Incontinence: More Prevalent in Women
Women with OAB (n = 463) With UUI 55% Men with OAB (n = 401) With UUI 16% Without UUI 45% National Overactive Bladder Evaluation Study Without UUI 84% Stewart WF, et al. World J Urol. 2003;20:327-336.
Overcoming Barriers in OAB: Forming an Accurate Diagnosis
Patients Suffer Needlessly From OAB
•
OAB negatively impacts QOL:
– – – – – – – –
Emotional well-being Social relationships Productivity Physical functioning Anxiety Hostility Depression Avoid activities like travel
• •
Patients Would Rather Cope With OAB Than Seek Help Due to:
•
Fear of embarrassment Fear resulting from misconceptions Differences in perception:
–
Symptom severity
– –
Degree of bother Willingness to seek treatment
Khullar V, et al. Urology. 2006;68(2 suppl):38-48.
Dmochowski RR, et al. Curr Med Res Opin. 2007;23:65-76.
OAB Symptoms Negatively Affect Patients
100 80 60 59.3
A lot Moderately A little Omitted or not applicable 49.2
40 20 32.5
47.3
33.5
16.7
7.2
1.0
0 Frequency Nocturia HRQOL assessed with King’s Health Questionnaire N = 2878 2.4
30.3
14.8
5.6
Urgency 38.1
31.3
20.5
10.1
UUI Sand P, et al. BJU Int. 2007;99:836-844.
Women Prefer Clinicians to Initiate Discussion About Urinary Symptoms
•
50 40 30 20 10 37 35 33 43 0 Total (n = 1046) SUI (n = 386) UUI (n = 271) MUI (n = 389) Participant question: “I would be more comfortable discussing urinary symptoms if my health care provider brought up the topic.” SUI: stress urinary incontinence MUI: mixed urinary incontinence MacDiarmid S, et al. Curr Med Res Opin. 2005;21;1413-1421.
Look for Comorbidities of OAB
30 25 28.0
25.3
OAB Control 20 15 10 5 0 4.7
1.8
P < 0.0001 3.9
2.3
10.5
4.9
8.4
16.1
Vulvovaginitis Skin infections Depression UTIs Falls and fractures
•
These conditions were 2.8 times more likely to occur in patients with OAB compared to controls (95% CI, 2.6-2.9):
– Adjusted for neurologic conditions, diuretic use, potentially inappropriate drug use, and UTI risk factors
11,556 adult patients with OAB and 11,556 controls matched on propensity score Adapted from Darkow T, et al. Pharmacotherapy. 2005;25:511-519.
How Do You Approach a Conversation About Urinary Problems Like OAB?
?
1.
I ask 1 or more questions like, “Do you have urinary problems?” 2. I let the patient bring it up 3. I use a questionnaire 4. I do not routinely ask about urinary problems
How to Optimally Obtain a Patient History:
First Line of Questioning
• • •
Do you have urinary problems?
1,2 How much do the symptoms bother you?
Do you want medication for your problems?
1 Lavelle JP, et al. Am J Med. 2006;119(3 suppl 1):37-40.
2 Rosenberg MT, et al. Cleve Clin J Med. 2005;72:149-156.
How to Optimally Obtain a Patient History:
Second Line of Questioning
How are you handling your urinary symptoms?
Urgency Frequency Nocturia UUI
What is your most distressing symptom?
How long have you experienced these symptoms?
What is your fluid intake?
What have you tried to solve your problems?
• •
Do you have to rush to go to the toilet? Do you have to urinate IMMEDIATELY?
•
Do you feel that you urinate too often during the day?
• •
Do you have to get up during the night to urinate? Is it the urge to urinate that wakes you?
•
When you feel the urge to urinate, do you have leaks or wetting accidents?
Rosenberg MT, et al. Cleve Clin J Med. 2005;72:149-156.
Irwin DE, et al. Eur Urol. 2006;50:1306-1314.
Marschall-Kehrel D, et al. Urology. 2006;68(2 suppl):29-37.
How to Optimally Obtain a Patient History:
Elements of the Examination
•
Now that the urinary problem is identified, inquire about:
– – – – –
Lower urinary tract symptoms (LUTS) Medical and surgical history Medications Focused physical examination Laboratory examinations and/or tests:
• Voiding diary, pad test
Lavelle JP, et al. Am J Med. 2006;119(3 suppl 1):37-40.
Rosenberg MT, et al. Cleve Clin J Med. 2005;72:149-156.
Clinical Practice Recommendation
• • • •
Practice recommendation:
–
Patient history in combination with pad tests and urinary diaries is effective in diagnosing OAB
Evidence-based source:
–
Health Technology Assessment
Web site of supporting evidence:
–
http://www.ncchta.org/fullmono/mon1006.pdf
Strength of evidence:
–
Of 6009 papers, 121 were relevant for inclusion in the review:
• Comparison of 2 or more assessment/diagnostic techniques –
Simple investigations (eg, pad test and diary) may offer useful information on severity
–
Combined with history, process may provide sufficient information to commence primary care interventions (which are low cost and low risk)
Case Study 1: Carol
Presentation
• • • •
Carol, aged 55 years, has been a long-term patient of yours and presents to your office to check on her hypertension and get a new prescription She seems hesitant to leave after the examination and you question her on other troubling symptoms She admits to experiencing OAB symptoms with great bother:
–
Frequency has increased in the past 6 months
–
Nocturia
Medical history:
–
Previously treated for depression and UTIs
– –
Hypertension treated with diuretic and calcium channel blocker Atrophic vaginitis testing was unremarkable
What Is Your Initial Approach to Treating Carol?
?
1. Behavioral modifications 2. Pharmacotherapy 3. Combination of behavioral modifications and pharmacotherapy 4. I ask the patient for her treatment goals and preference first 5. I do not treat OAB
Behavioral Modifications Are a Good Starting Point
• •
Bladder training: scheduled voiding/voiding deferment 1,2 Pelvic floor exercises 1-4 :
– – – –
Can be easily performed at home with no equipment needed Not associated with significant adverse events Significant impact in women with UUI and MUI Evidence for men lacking
•
Significantly higher cure rates and satisfaction associated with combined bladder training and pelvic floor exercises than either therapy alone 4 1 Christofi N, et al. Menopause Int. 2007;13:154-158.
2 Newman DK. Am J Nurs. 2002;102:36-45.
3 Burgio KL. J Am Acad Nurse Pract. 2004;16(10 suppl):4-7.
4 Milne JL. J Wound Ostomy Continence Nurs. 2008;35:93-101.
Clinical Practice Recommendation
• • • •
Practice recommendation:
–
Behavioral therapy improves symptoms of UUI and MUI
Evidence-based source:
–
National Guideline Clearinghouse
Web site of supporting evidence:
–
http://www.guideline.gov/summary/summary.aspx?doc_id=1093 1&nbr=005711&string=incontinence
Strength of evidence:
– –
Level A Can be recommended as a noninvasive treatment in many women
Lifestyle Modifications in OAB: Current Evidence Is Sparse and Inconsistent
• • •
Caffeine reduction dose dependent 1 :
–
Affects patients consuming ≥ 400 mg caffeine or 2.5 cups of coffee
Weight loss 1 :
–
Significant reduction in UUI reported:
• No data in men or in OAB dry or moderately overweight patients
Adjusting fluid intake 1,2 :
– –
Greater impact than caffeine restriction For significant improvement in urgency, frequency, and nocturia episodes, modify fluid input by 25% (goal: 1500-2400 mL/day)
•
Few data for smoking cessation and regulation of bowel function 2 1 Milne JL. J Wound Ostomy Continence Nurs. 2008;35:93-101.
2 Newman DK, et al. Am J Nurs. 2002;102:36-45.
Case Study 1: Carol
Treatment
• • •
Low-dose antimuscarinic with daily dosing Take diuretic before bedtime to improve nocturia Behavioral modifications
OAB in Female Patients
Differential Diagnosis of Symptoms in Women With OAB
Women UTI Bladder cancer Diabetes Multiple sclerosis SUI Recent pelvic surgery Neurogenic bladder Prolapse Urethral obstruction Atrophic vaginitis Postsurgical incontinence Rosenberg MT, et al. Cleve Clin J Med. 2007;74(suppl 3):S21-S29.
ICI Management of Incontinence in Women
Incontinence on physical activity Incontinence with mixed symptoms Incontinence with urgency/frequency SUI Evaluation MUI UUI Pelvic floor muscle training Bladder retraining Treat most bothersome symptoms for MUI ICI: International Consultation on Incontinence Antimuscarinics Adapted from Kirby M, et al. Int J Clin Pract. 2006;60:1263-1271.
Treatment Strategies and Pharmacotherapy for OAB
David R. Staskin, MD
New York Presbyterian Hospital New York, NY
Treatment Goals for OAB
Eliminate or improve UUI Reduce urgency - frequency - incontinence - nocturia Improvement in warning time Ensure treatment compliance for multiple long-term benefits:
-
Consider appropriate dose, comorbidities, cost, and improved QOL
Consensus with the patient’s treatment expectations Hegde SS. Br J Pharmacol. 2006;147(suppl 2):S80-S87.
Staskin DR, et al. Am J Med. 2006;119(3 suppl 1):9-15. Cardozo L, et al. J Urol. 2005;173:1214-1218.
Patient and Physician Expectations
Overall Expectations of Treatment 1 Complete Cure Improved QOL
• • • • •
Tailor to 2 :
Environment Expectations Lifestyle Age Health
Physicians 3.2% 85.9% Patients 17% 43%
• • • • • •
Not tailoring treatment may lead to 2 :
Disillusionment Avoidable adverse events Unneeded use of time and resources Harmful and unnecessary surgery Morbidity/mortality Worsening symptoms
1 Robinson D, et al. Int Urogynecol J Pelvic Floor Dysfunct. 2007;18:273-279.
2 Cardozo L. BJU Int. 2007;99(suppl 3):1-7.
Clinical Practice Recommendation
• • • •
Practice recommendation:
–
Antimuscarinics significantly reduce OAB symptoms
Evidence-based source:
–
Cochrane Database of Systematic Reviews
Web site of supporting evidence:
–
http://www.cochrane.org/reviews/en/ab003781.html
Strength of evidence:
– –
61 trials included in the review The use of anticholinergic drugs for OAB results in statistically significant improvements in symptoms
Symptom-Based OAB Management
100
Patient perception of improvement in overall bladder condition at week 12* 1
Major improvement Minor improvement 80 60 40 20 28.3
58.0
29.7
48.3
29.9
48.6
24.9
49.7
28.4
50.4
Questionnaires used:
OAB symptom questionnaire (OAB-q) American Urological Association Symptom Index Patient Perception of Bladder Condition (PPBC)
0 Urgency Frequency (day) Nocturia UUI Total
• •
863 patients from 82 primary care and 16 obstetric/gynecology offices 1,2
OAB symptoms ≥ 3 months; at least moderately bothered by most bothersome symptom 69% of patients had ≥ 1 comorbid condition; none of the patients had retention requiring catheterization
* IMPACT: tolterodine extended release (ER) 12-week, open label study 1 Roberts R, et al. Int J Clin Pract. 2006;60:752-758.
2 Elinoff V, et al. Int J Clin Pract. 2006;60:745-751.
Pros and Cons: Antimuscarinics
PROS Only approved treatments with grade A recommendation Extensive literature has demonstrated efficacy and improved QOL Data available from large-scale, randomized controlled trials Alternative surgical treatments limited by morbidity and cost Good tolerability CONS Physiology/uropharmacology still does not provide ideal agent Adherence to therapy is low High placebo rates Response to behavioral therapies Anticholinergic side effects Adapted from Chapple C, et al. Eur Urol. 2008;54:226-230.
Potential Adverse Events, Contraindications, and Drug Interactions of Antimuscarinics
Most common side effects Rare/potential adverse events Dry mouth 1,2 Constipation 1,2 Blurred vision 1,2 Sedation, cognitive effects 2,3 Drowsiness, headache 4 Cardiac adverse effects (QT prolongation) 4 Heat prostration (decreased sweating) 4 Contraindications Urinary or gastric retention 4 Uncontrolled narrow-angle glaucoma 4 Drug interactions Antidepressants* 2,3 Polypharmacy in the elderly 2 CYP3A4 inhibitors †3,5 Diuretic effect of alcohol 2 * eg, paroxetine (SSRI) shares CYP2D6 1 Steers WD. Urol Clin North Am. 2006;33:475-482.
† liver metabolism with darifenacin eg, ketoconazole, fluoxetine (SSRI) 4 Physicians’ Desk Reference. 62nd ed. Montvale, NJ: Thomson PDR; 2008.
SSRI: selective serotonin reuptake inhibitor 5 2 Erdem N, et al. Am J Med. 2006;119(3 suppl 1):29-36.
3 Staskin DR. Drugs Aging. 2005;22:1013-1028.
Swart PJ, et al. Basic Clin Pharmacol Toxicol. 2006;99:33-36.
Adverse Events Decline Over Time*
50 40 Consistent finding across long-term studies for OAB: adverse events are most common within 3 months of therapy and decline thereafter 30 20 Dry mouth Constipation 10 0 0 to 3 > 3 to 6 > 6 to 9 > 9 to 12 > 12 to 15 > 15 to 18 Treatment duration (months) > 18 to 21 N = 716 * 24-month, noncomparative, darifenacin, open-label extension study > 21 to 24 > 24 Haab F, et al. BJU Int. 2006;98:1025-1032.
Enhanced Therapeutic Effects With Combined Pharmacologic and Behavioral Therapy
Behavioral therapy 0 –10 –20 –30 –40 –50 –60 –70 –80 –90 –57.5
–100 P = 0.034
N = 197 * Behavioral therapy and pharmacotherapy Combined therapy* –88.5
Pharmacologic therapy Combined therapy* –72.7
P = 0.001
–84.3
Burgio KL, et al. J Am Geriatr Soc. 2000;48:370-374.
Outcome Measures 1. Objective versus subjective measures 2. Metrics for urgency:
–
Urgency severity
–
Warning time
Correlation of Subjective and Objective Measures
Patient-Reported Outcomes (PROs)
•
Meaningful improvements for the patient
•
Changes captured by PROs may differ and include more information than those captured by bladder diaries Tools
•
Bladder diaries
•
OAB-q:
–
8-item Symptom Bother scale
–
25-item HRQOL scale (concern, sleep, social interaction, and coping)
•
PPBC:
–
Single item of 6 statements
Coyne KS, et al. Int J Clin Pract. 2008;62:925-931.
Metrics for Urgency: Reduction in Urgency Severity
1 Weeks 4 12 0 –0.1
–0.2
P = 0.0002
–0.3
P = 0.0008
–0.4
Trospium 60 mg daily (n = 292) Placebo (n = 300) P = 0.0004
–0.5
Trospium significantly reduced urgency severity episodes in patients with OAB IUSS: Indevus Urgency Severity Scale Staskin D, et al. J Urol. 2007;178(3 pt 1):978-983.
Antimuscarinics and Warning Time in OAB: Impact of Urgency
50 First study to demonstrate significant increase in warning time in a large clinical setting (VENUS)
(n = 739; solifenacin vs placebo) 1
40 31.5
*
30 20 12.0
10 (n = 372) (n = 367) 0 Solifenacin
(5-10 mg daily)
Placebo * P = 0.032
Primary end point: mean reduction in urgency episodes per 24 hours: 3.91 for solifenacin vs 2.73 for placebo (P < 0.001) 1 Toglia M, et al. Neurourol Urodyn. 2006;25:655. Abstract 123. 2 Zinner N, et al. Int J Clin Pract. 2006;60:119-126.
• • •
Warning time:
–
Time from first sensation of urgency to voiding 1-3
Increase in warning time significant to patients 1-3 :
–
More time to reach a toilet
–
Avoid urge incontinence episodes
Other warning time placebo controlled studies:
–
Darifenacin 15 mg daily (P = not significant; N = 432) 2
–
Darifenacin 30 mg daily (P = 0.003; N = 67) 3
–
Oxybutynin 2.5 mg TID (P < 0.001; N = 44) 4
3 Cardozo L, et al. J Urol. 2005;173:1214-1218. 4 Wang AC, et al. Urology. 2006;68:999-1004.
Optimizing Treatment Success: Using Flexible-Dosing Options
OAB Patients Frequently Request Dose Adjustments
Percent of patients requesting a dose increase at 4 weeks* 1 48% Solifenacin 5 mg (n = 578) Solifenacin 10 mg Higher dose (10 mg) available 51% Tolterodine ER 4 mg + placebo Tolterodine ER 4 mg (n = 599) Higher dose not available Start 4 weeks 12 weeks
•
Similar results (59% vs 68%) were obtained after 2 weeks by a 12-week efficacy, safety, and tolerability study of darifenacin vs placebo 2 * Prospective 12-week, parallel-group, double-dummy, 2-arm, double-blind, efficacy and safety study 1 Chapple CR, et al. Eur Urol. 2005;48:464-470.
2 Steers W, et al. BJU Int. 2005;95:580-586.
Antimuscarinic Flexible Dosing (1)
STAR Study: Incontinent Patients Reporting No Incontinence Episodes at End Point on a 3-Day Diary*
100 80 60 40 20 0 59 † 49 Solifenacin Tolterodine ER Baseline (per 24 hours): 2.77 episodes 2.55 episodes * Patients who reported experiencing incontinence episodes per 24 hours at baseline and who did not report any episodes of incontinence for 3 consecutive days prior to the study visit † P = 0.006 vs tolterodine ER Chapple CR, et al. Eur Urol. 2005;48:464-470.
Antimuscarinic Flexible Dosing (2)
Flexible-Dosing Study
Reduction in incontinence episodes per week with darifenacin
0 No Dose Escalation 7.5 mg 7.5 mg (n = 104) -20 -40 -60 -49.2
-61.3
-80 Dose Escalation 7.5 mg (n = 157) -35.7
■ ■ 2 weeks 12 weeks 15 mg -64.8
Placebo 0 mg -28.6
0 mg (n = 127) -48.1
Steers W, et al. BJU Int. 2005;95:580-586.
Antimuscarinic Flexible Dosing (3)
Cumulative Response Rate With Increasing Dose
5 mg 10 mg 15 mg 20 mg 25 mg 30 mg 100 80 60 40 20 0 ≥ 70% decrease in urge episodes Complete dryness N = 368 MacDiarmid SA, et al. J Urol. 2005;174(4 pt 1):1301-1305.
Dosing Options Comparison
Antimuscarinic Darifenacin
7.5 and 15 mg
Oxybutynin IR
5 mg
ER
5, 10, 15 mg
TDS
3.9 mg/day system
Daily Dosing BID, TID, QID Daily (up to 30 mg/day) New patch twice a week (every 3-4 days) Dose Adjustment?
YES NO YES NO Solifenacin
5 and 10 mg
Tolterodine ER
4 mg
Daily Daily YES NO Trospium chloride*
20 mg 60 mg
BID Daily NO NO * 1 hour before meal or on an empty stomach IR: immediate release TDS: transdermal delivery system Physicians’ Desk Reference. 62nd ed. Montvale, NJ: Thomson PDR; 2008.
Low Patient Persistence
Medicaid and Prescription Drug Databases
100 80 60
Only 44% out of 1637 Medicaid patients remained persistent after 30 days
Tolterodine ER Oxybutynin ER
•
Low adherence and persistence reported by various clinical studies 2-4 :
–
Adherence rates reported for OAB similar to other chronic diseases 5
–
Low level of education and cultural and social support factors may contribute to poor compliance 6
40 20
•
Antimuscarinic therapy for OAB 3,5-6 :
–
Short- and long-term efficacy for significant proportion of users
–
Therapeutic/patient perceived benefits require at least 4-8 weeks of continuous therapy
0 0 30 60 90 12 0 15 0 18 0 Days 21 0 24 0 27 0 30 0 33 0 36 0 Persistence: time to discontinuation 1 Adapted from Shaya FT, et al. Am J Manag Care. 2005;11(4 suppl):S121-S129. 2 Chui MA, et al. Value Health. 2004;7:366. Abstract PUK11. 3 Yu YF, et al. Value Health. 2005;8:495-505. 4 Balkrishnan R, et al. J Urol. 2006;175(3 pt 1):1067-1071. 5 Basra RK, et al. BJU Int. 2008. Epub ahead of print.
6 Thomas L, et al. J Manag Care Pharm. 2008;14:381-386.
Factors Affecting Adherence
• • • • • •
Presentation and efficacy of medication Cost (financial or personal) Dosing frequency Expectations of treatment Route of administration of medication Adequate follow-up after initiation of therapy Follow-up is important to ensure patient adherence to treatment Basra RK, et al. BJU Int. 2008. Epub ahead of print.
D’Souza AO, et al. J Manag Care Pharm. 2008;14:291-301.
OAB in Male Patients
Case Study 2: Tom
Presentation
• • • •
Tom, aged 60 years, presents to your office for his annual physical examination At the end of the examination, he asks about the definition of normal voiding:
– – –
Works at night Frequent bathroom visits interrupt his work Slow urine stream and feeling that bladder has not emptied completely
Unremarkable medical history and physical examination:
–
Checked blood sugar levels
Normal laboratory values
Differential Diagnosis of Symptoms in Men With OAB
Men Benign prostatic hyperplasia (BPH) Prostate cancer Diabetes Postsurgical incontinence Bladder outlet obstruction (BOO) Urethral stricture Neurogenic bladder Bladder stones Rosenberg MT, et al. Cleve Clin J Med. 2007;74(suppl 3):S21-S29.
Men With OAB: LUTS
Storage and Voiding Symptoms
Storage 1,2
(afferent, irritative)
Urgency Frequency Nocturia UUI
SUI
MUI
Overflow incontinence
Voiding 1,2
(efferent/obstructive)
Hesitancy Poor flow/weak stream Intermittency Straining to pass urine Terminal dribble Prolonged micturition Urinary retention
Postmicturition 1,2
Postvoid dribble
Sense of incomplete emptying
1 Abrams P, et al. Neurourol Urodyn. 2002;21:167-178.
2 Chapple CR, et al. Eur Urol. 2006;49:651-658.
LUTS Watchful waiting
Clinical Algorithm for the Management of LUTS in Men
No Focused history and physical examination Urinalysis/PSA Blood sugar Unlikely BPH or OAB Referral and/or treat Desires treatment Check PVR Provisional OAB Ineffective Trial Provisional BPH α-blocker Effective Continue medication < 50 cc PSA: prostate-specific antigen PVR: postvoid residual 50-200 cc > 200 cc Referral Rosenberg MT, et al. Int J Clin Pract. 2007;61:1535-1546.
Clinical Algorithm for the Management of LUTS in Men
(Cont.)
Check PVR Possible OAB High < 50 cc Uroflow Diagnosis unclear Low Mixed OAB/BPH 50-200 cc
• • • •
Optional Titrate
α
-blocker Switch medication Try ARI, combination therapy Refer Ineffective > 200 cc Effective Referral Continue therapy Antimuscarinics High Uroflow Low Referral Effective Ineffective Referral Continue medication ARI: α-reductase inhibitor Rosenberg MT, et al. Int J Clin Pract. 2007;61:1535-1546.
Low Risk of Retention in Men on Antimuscarinics for OAB/LUTS
Evidence From Trials
Study/Goal Result Reference(s) Antimuscarinic monotherapy in men with BOO/DO versus placebo No clinically meaningful change in PVR or urinary retention Combined therapy: α-blocker plus antimuscarinics in men Increased benefit with combination therapy Low incidence of retention Varying results for PVR increase Antimuscarinic therapy in men with OAB with or without BPH medication Low incidence of retention, no catheterization Abrams P, et al. J Urol. 2006;175(3 pt 1):999-1004.
(Tolterodine ER)
Kaplan SA, et al. JAMA. 2006;296:2319-2328.
(Tolterodine ER plus tamsulosin)
Lee K-S, et al. J Urol. 2005;174(4 pt 1):1334-1338.
(Propiverine hydrochloride* plus doxazosin ER)
Staskin DR, et al. Int J Clin Pract. 2008;62:27-38.
(Oxybutynin TDS)
* Not available in the United States DO: detrusor overactivity
OAB Symptom Improvement in Men: Patient-Reported Outcomes
■ PPBC = 1, 2, or 3 ■ PPBC = 4, 5, or 6 100 80 60 40 20 0 Baseline 1 2 3 4 5 Month ■ Always ■ ■ Most of the time Sometimes, infrequently, or never 100 80 60 40 20 0 Baseline 1 2 3 N = 369 men with PPBC ≥ 4 (condition caused moderate, Month severe, or many severe problems) 4 5 6 6
•
Antimuscarinic treatment effective and well tolerated in men with OAB:
–
Regardless of history of “prostate condition”
Global assessment of OAB severity “Within the past month, do you feel that you had enough time to get to the bathroom?” MATRIX: open-label study with oxybutynin TDS Staskin DR, et al. Int J Clin Pract. 2008;62:27-38.
Case Study 2: Tom
Treatment and Follow-Up
• • •
You use a questionnaire to assess Tom’s symptoms Behavioral modifications You start him on an α-blocker:
–
At follow-up, obstruction has improved
•
He still complains of nocturia and you add antimuscarinic treatment:
–
After 4 weeks of antimuscarinic treatment, his nocturia episodes have been reduced to 2 times a night
Summary
• • •
OAB is a prevalent disease that increases with age OAB impacts comorbidities and QOL OAB symptoms can be treated:
– –
Move toward symptom/syndrome-based treatment Individualized to match patient’s preference and expectations (tolerability and efficacy)
– – –
Recognize comorbidities and treatment fluid imbalances Institute behavioral changes and pelvic floor exercises Flexible-dosing regimens
Postmeeting Survey
•
True or false: The core symptom of OAB is urgency.
1. True 2. False
?
Postmeeting Survey
•
Which of the following are NOT considered comorbidities in patients with OAB?
1.
2.
3.
4.
Falls and fractures UTIs Skin infections Kidney stones
?
Postmeeting Survey
•
True or False: Using a flexible-dosing regimen of antimuscarinics results in improved efficacy and patient satisfaction.
1. True 2. False
?
Generic Darifenacin Doxazosin Fluoxetine Ketoconazole Oxybutynin Paroxetine Propiverine Solifenacin Tolterodine Trospium
Generic/Brand Name Table
Trade Enablex ® Cardura ® Prozac ® , Sarafem ® Extina ® , Nizoral ® , Xolegel ® Ditropan ® , Oxytrol ® Paxil ® , Pexeva ® Not available in the United States VESIcare ® Detrol ® Sanctura XR™