Final slide deck for dr iglesiaPresentation Transcript
Faculty DisclosureDr. Iglesia has no relevant conflictsto disclose.
Objectives• Develop effective treatment plans for women with overactive bladder.• Describe how to communicate realistic goals of overactive bladder treatment with patients.• Review how to minimize medication side effects in treatment plans for women with overactive bladder.• Describe the efficacy and safety of new and emerging therapies for women with overactive bladder.
Urinary Incontinence (UI): Prevalence • 13 million Americans • Gender – Female: 10%-55% – Male: 2%-5% • Prevalence and severity increase with age • Seen in over 50% of nursing home patients
Changing the Face of UIStereotype RealityFor illustrative purposes only. Not indicative of population distribution.
Prevalence of Any UI By Age and SeverityMinassian VA, et al. Obstet Gynecol. 2008;111(2 Pt 1):324-331.
Prevalence of Urge UI By Age and SeverityMinassian VA, et al. Obstet Gynecol. 2008;111(2 Pt 1):324-331.
Patient Case: Background (1)• Mrs. D is a 48-year-old, perimenopausal, White female.• Approximately one month ago, she began experiencing urgency, frequency, and occasional urge urinary incontinence (UI).• In the past 6 months she has gained nearly 25 lbs, which she attributes to perimenopause. She now has a BMI of 28.5.
Patient Case: Background (2)• She has noticed a significant decline in sexual desire and satisfaction since the onset of her bladder problems.• She feels anxious and is nervous that she will embarrass herself in public.• She takes HCTZ and propranolol for hypertension, and SSRI for mild depression.
Defining Overactive Bladder The International Continence Society defines OAB as: • Urinary urgency, with or without urge incontinence, usually with urinary frequency and nocturia, in the absence of pathologic or metabolic factors that would explain these symptoms Therefore, ask about URGENCYNational Association for Continence (2008) www.nafc.org
Major Types of Urinary IncontinenceStressUrgeOverflow Transient Functional
OAB in the United States Incontinent Versus Continent: NOBLE 12.2 million (6.1% of the population) 37% 33.3 Incontinent million OAB (>16% of pop.) 63% Continent 21.2 million (10.5% of the adult population)Stewart WF, et al. World J Urol. 2003;20(6):327-336.
Impact on Quality of Life: The Silent Sufferers Physical Psychological • Limitations or • Guilt/depression cessation of physical • Loss of self-esteem Sexual activities • Fear of: • Avoidance of sexual – Being a burden contact and – Lack of bladder intimacy control Quality – Urine odor Occupational • Absence from work of Life Social • Reduction in social • Decreased interaction productivity • Limit and plan travel Domestic around toilet accessibility • Require specialized underwear, bedding • Special precautions with clothingTubaro A. Urology. 2004;64(6 suppl 1):2-6.
Lower Urinary Tract Function• Bladder and urethral functions – Storage – Micturition• These functions are controlled by the central nervous system (CNS) through reflexes that coordinate the activity of: – Bladder (smooth muscle) – Urethra (smooth and striated muscles) – Pelvic floor muscles
Initial Assessment• Medical history• Screening questions• Urinalysis• Physical examination
Evaluation and Management• Urinalysis• Simple pelvic examination
Patient Case: Continued• Based on her assessment, you learned she suffers from constipation and has tried to increase her water intake to address that issue.• With further questioning, she also reports that she has been getting up to urinate at least 4 times a night. – Is it nocturia or nocturnal polyuria?
Screening: Intake/Output Diary
Nocturia vs Nocturnal Polyuria • Assessed with simple 24-hour urine collection • Common causes: Sleep apnea, CHF, diabetes mellitus • Sleep apnea – Most under-recognized cause of nocturnal polyuria – Treatment with CPAP significantly reduces nocturic frequencyFitzgerald MP, et al. Am J Obstet Gynecol. 2006;194(5):1399-1403.
Behavioral Interventions • Behavioral Training Techniques – Pelvic floor muscle (PFM) training • Physical therapy (PT) • Kegel exercises – Bladder training: • Biofeedback • Timed voiding • Behavioral Modification – Lifestyle modifications: Eliminating bladder irritants from diet, managing fluid intake, weight control, monitoring bowel regularity, smoking cessation, and patient educationWyman J, et al. Int J Clin Pract. 2009;63(8):1177-1191.
Pelvic Muscle Rehabilitation
Pelvic PT and Exercise Adherence Study • Less than ¼ of women continued exercises. • No difference in rate of subsequent SUI surgery in women who had intensive pelvic PT vs those who did not. • Marked benefit of initial therapy not maintained 15 years later.Bo K, et al. Obstet Gynecol. 2005;105(5 Pt 1):999-1005.
Pelvic Floor Muscle (PFM) Training (Kegel Exercises)• Rationale: strong and fast PFM contraction increases urethral pressure and prevents leakage during sudden increase in abdominal pressure• Recommendation: – 3 sets of 8-12 slow-velocity maximum voluntary contractions, sustained for 6-8 seconds, performed 3-4 times a week for at least 15-20 weeks• Effectiveness: depends upon type of exercise, frequency, intensity, and duration of training
Weighted Vaginal Cones
Pessary for Incontinence:Useful for Stress, Not Urge Pessary in position
Behavioral Modification • Elimination of bladder irritants from diet – Eliminate stimulants, such as caffeine and over-the- counter prescription medication with caffeine. – Evidence suggests aspartame and other artificial sweeteners may contribute to OAB symptoms. • Smoking cessation – Smoking may cause chronic coughing, which in turn may increase the intra-abdominal pressure and cause UI. – Smoking cessation education should be offered, stressing the relationship between smoking and UI.Wyman J, et al. Int J Clin Pract. 2009;63(8):1177-1191.
Behavioral Modification (cont) • Management of fluid intake – When is too much, too much? – When is too little, not enough? • Management of bowel regularity – Avoid constipation – Increase dietary fiber – Engage in regular exercise – Establish regular defecation plan • Weight control – First-line option for treatment of UI for obese clients – Goal should be set to decrease BMI to <30 kg/m2Wyman J, et al. Int J Clin Pract. 2009;63(8):1177-1191.
Patient Case• Mrs. D eliminates caffeine from her diet; reduces her HTN medication; and tries do Kegel exercises regularly.• She is still experiencing some leaking and continued, though less frequent, night urgencies.• You suggest trying a pharmacologic agent.
STAR Trial: N=1200 • 12-week, European, prospective, randomized, double- blind, double-dummy, 2-arm, parallel-group trial • Dose titration regimen of solifenacin (5 mg or 10 mg qd) or a single dose of tolterodine LA 4 mg qd • Primary objective: Non-inferiority study • Primary endpoint: Micturition frequency • Secondary endpoints: Incontinence episodes, urge incontinence episodes, urgency, volume voided, and tolerabilityChapple CR, et al. Eur Urol. 2005;48(3):464-470.
STAR Trial Reported Endpoints Solifenacin Tolterodine Endpoint (pooled P value (4 mg qd) 5 mg/10 mg) PRIMARY (non-inferiority) [PPS]* (n=525) (n=524) Micturition frequency/24 h –2.45 –2.24 .004 SECONDARY (FAS)† (n=578) (n=599) Urgency episodes/24 h –2.85 –2.42 .035 Incontinence episodes/24 h –1.60 –1.11 .006 Nocturia episodes –0.71 –0.63 .730 Urge incontinence episodes/24 h –1.42 –0.83 <.01 Mean volume voided (mL/void) 38.00 31.00 .01 Patients dry (%) 59.00 49.00 .006 Pads/24 h –1.72 –1.19 .0023 Perception of bladder condition –1.51 –1.33 .0061Chapple CR, et al. Eur Urol, 2005:48(3):464-470. *Per protocol set. †Full analysis set.
Darifenacin • Bladder selectivity (marginal) in animal studies: Not more than tolterodine or oxybutynin in guinea pigs • Multicenter, placebo-controlled RCT (n=561) • Reduction in incontinent episodes: – 67.7% Darifenacin 7.5 mg (P = .010) – 72.8% Darifenacin 15 mg (P = .017) – 55.9% Placebo – No reductions in nocturiaHaab F, et al. Eur Urol. 2004;45(4):420-429.
Darifenacin and Warning Time? Difference in Medians at Week 2 = 4.3 minutes (P = .003) 8 7 6 5 4 Baseline Week 2 3 2 1 0 Darifenacin 30 mg n 0 g Placebo o n=32 n=35Cardozo L, et al. J Urol. 2005;173:1214-1218.
Non-Selective Muscarinic Antagonists: Trospium • Quaternary amine • Used in Europe for 20 years: Many studies • Efficacy not different from standard agents • Poor bioavailability • RCT in US (phase 3, N=523):* – 20 mg bid – Urge UI: 59% drug vs 44% placebo – Nocturnal frequency decreased by week 4 – Side effects: Dry mouth 21.8%*Zinner N, et al. J Urol. 2004;171(6 Pt 1):2311-2315.
Tailor Therapy to Each Patient to Improve Adherence• Does it fit into their schedule? Do they need reminders to take?• Cost: Have you reviewed formularies, copayments, availability of generics?• Do they understand how long it might take to work? Is it working for them?• Can you reduce potentiality of side effects?
Side Effects• Dry mouth (higher than M2 agents)• Constipation (higher than M2 agents)• Blurred vision• Exacerbation of gastroesophageal reflux• Cardiac changes• Urinary retention
CNS Considerations in the Treatment of Overactive Bladder: Passive Diffusion Across the BBB Vasculature BBB CNS ↑ Lipophilicity ↑ Diffusion ↑ Charge/polarity, + + - - hydrogen bonding + + - + - -+ - - ↓ Diffusion + ↓ Molecular “bulkiness” ↑ DiffusionPardridge WM. J Neurochem. 1998;70:1781-1792.Habgood MD, et al. Cell Mol Neurobiol. 2000;20:231-253. BBB: blood-brain barrier
Effect of Darifenacin and Oxybutynin ER on Memory in Older Subjects • 3-week, randomized, double-blind, double-dummy, parallel-group, placebo-controlled, multicenter study • 150 healthy volunteers ‑ age range 60–83 (12.7% ≥75 years) ‑ 62% female • 2-week screening to assess eligibility • Active treatments administered according to US prescribing information • Computerized battery of cognitive function tests assessed effect of each drug at end of weeks 1, 2, & 3Kay GG, et al. Eur Urol. 2006;50:317-326.
Primary Endpoint: Delayed Memory Recall in The Name-Face Association Test Score for accuracy (least square mean) Mean Score for delayed recall Name-Face Association Test *† *† Darifenacin (n=46) Oxybutynin ER (n=49) Placebo (n=50) Week *P < .05 vs placebo; †P < .05 vs darifenacinReprinted with permission from Elsevier (ANCOVA, adjusted for baseline score, age, and sex)Kay GG, et al. Eur Urol. 2006;50:317-326. Patient (n) numbers reflect baseline values
Self-Rated Memory Assessment (MAC-S) MAC-S score (least square mean) Darifenacin (n=46) Oxybutynin ER (n=49) Placebo (n=50) Patient (n) numbers reflect baseline valuesKay GG, et al. Eur Urol. 2006;50:317-326.Novartis Pharmaceuticals. Data on File
Alternative Therapies/Treatments• Botulinum• InterStim Therapy• Tension-Free Vaginal Tape- only for mixed UI
Tension-Free Vaginal Tape
Treatment for OAB: Never Surgery• Mixed UI may be managed with mid- urethral slings, but efficacy is lower than pure SUI
Conclusions• UI is common.• Most women go untreated.• Highly efficacious therapies exist.• Encourage women to be proactive about treating quality-of-life conditions.