The Problem Stress Urine loss with increased intraabdominal - - PowerPoint PPT Presentation

TREATMENT OPTIONS FOR OVERACTIVE BLADDER Leslee L. Subak, MD

Professor Obstetrics, Gynecology & RS Epidemiology, Urology University of California, San Francisco

No Conflicts of Interest

The Problem

Urinary Incontinence: High prevalence, High cost, Low intervention rate

Chronic Conditions

Kaiser Family Foundation, 2008

• Types of Urinary Incontinence

Stress Urine loss with increased intraabdominal pressure, like with coughing, sneezing, lifting, exercising Urgency Urine loss associated with a sudden, strong desire to

• urinate. Occurs with muscle contractions/instability.

Mixed Stress and urge incontinence together Functional Loss of bladder control due to factors not related to the urinary tract, like physical disability, external

• bstacles, or problems in thinking or communicating

Overflow Dribbling or continuous leaks due to urinary retention

Stress vs. Urgency Incontinence

Characteristic Stress UI OAB/Urge UI Etiology Support OAB/DI Precipitant activity urgency Timing immediate delayed Amount small-mod large Frequency rare common Nocturia rare common

Overactive Bladder (OAB) Overactive Bladder (OAB)

Prevalence: 8-31% of women

• Frequency: >8 voids per day
• Urgency: sudden compelling desire

to void; difficult to defer

• Nocturia: >2 voids per night
• Urgency urinary incontinence (UUI)

Abrams P et al. Neuourol Urodyn. 2002;21:167

UI: Who is at Risk?

Risk Factor Risk Age (per 5 years) 30% Live birth 30% Modifiable or Preventable Oral estrogen 90% Stroke 90% Diabetes 70% BMI (per 5 units) 60% Poor overall health 60% Hysterectomy 40% COPD 40%

Sampselle 2002; Jackson 2004; Hannestad 2003; Waetjen 2006; Melville 2005; Danforth 2006; Ebbesen 2006; Wetle 1995; Brown 1996

Modifiable Contributing Factors for UI

• Obesity
• Diabetes
• Oral estrogen
• UTI
• Constipation
• Mobility impairment
• Liquids, caffeine, EtOH
• Drugs: diuretics, ACE inhibitors,

sedatives, hypnotics

< 1/3

seek treatment

Incontinence is embarrassing!

< 1/3

seek treatment

Don’t tell: Patients

• Few women seek care: 20-30%
• Not discussed with other women
• Treatments: lack knowledge, fear of surgery
• Failed communication with provider

Shaw 2001; Roe 1999; Seim 1995; Mitteness 1995; Burgio 1994

Don’t ask: PCC

Practice Guidelines: History, diary, pelvic exam, stress cough test, post void residual (PVR), U/A, 24 hr pad test

• U.S. PCC reality check:

− 15 minute appointments − no pelvic exam tables − PVR not possible

Too cumbersome for US primary care

Diagnostic Aspects of Incontinence Study (DAISy)

• Multi-center study (N=301)
• 3 Incontinence Questions (3 IQ) vs.

Extended Evaluation

− US, UK, WHO: Clinical Practice Guidelines − Extensive History − Exam: Neuro S2-S4, Pelvic exam − Tests: PVR, Cough Stress Test, UA − 3-Day Diary

Brown JS et al. Annals Internal Med 2006;144:715

3 Incontinence Questions (3 IQ)

• 1. During the last 3 months, have you leaked urine, even a small amount?

Yes

• No Questionnaire Completed.
• 2. During the last 3 months, did you leak urine: (Check ALL that apply.)

When you were performing some physical activity such as coughing, sneezing, lifting or exercise? When you had the urge or the feeling that you needed to empty your bladder but you could not get to the toilet fast enough? Without physical activity and without a sense of urgency?

• 3. During the last 3 months, did you leak urine most often: (Check only ONE)

When you were performing some physical activity such as coughing, sneezing, lifting or exercise? [STRESS] When you had the urge or the feeling that you needed to empty your bladder but you could not get to the toilet fast enough? [URGENCY] Without physical activity and without a sense of urgency? [OTHER] About equally as often with physical activity as with a sense of urgency? [MIXED]

Accuracy of 3 IQ Compared to Extended Evaluation

> Similar to other diagnostic tests

Brown JS. Annals 2006

VALIDATION OF 3IQ

• 3IQ: simple, inexpensive, feasible

− Reproducible (kappa 70% for urge and stress) − Acceptable accuracy for classification of incontinence

type

• Include a urinalysis (UA) in the evaluation
• Take Home Message

− 3IQ is a good test for type of UI in women − With 3IQ + UA, the risk of missed Dx and Rx is low Brown JS et al. Ann Intern Med. 2006;144:715

3 IQ in Action

• Ms. I. Gotta Go is a 60 yo teacher G0P0:
• “I have a hard time waiting until the end a class

to go to the bathroom and usually have to run to get there. Almost every day I leak on the way to the bathroom. When I have a severe cough, I may leak also but that occurs rarely.”

3 Incontinence Questions (3 IQ)

• 1. During the last 3 months, have you leaked urine, even a small amount?

Yes

• No Questionnaire Completed.
• 2. During the last 3 months, did you leak urine: (Check ALL that apply.)

When you were performing some physical activity such as coughing, sneezing, lifting or exercise? When you had the urge or the feeling that you needed to empty your bladder but you could not get to the toilet fast enough? Without physical activity and without a sense of urgency?

• 3. During the last 3 months, did you leak urine most often: (Check only ONE)

When you were performing some physical activity such as coughing, sneezing, lifting or exercise? When you had the urge or the feeling that you needed to empty your bladder but you could not get to the toilet fast enough? Without physical activity and without a sense of urgency? About equally as often with physical activity as with a sense of urgency?

X X X X

And the diagnosis is?

S t r e s s U I U r g e n c y U I M i x e d U I O t h e r U I

2% 2% 80% 16%

1.

Stress UI

2.

Urgency UI

3.

Mixed UI

4.

Other UI

3 IQ in Action

• Ms. Stressed is a 54 yo Techie G2P2:
• “Ever since my first birth, when I am physically

active - I leak urine. Recently, almost every day I leak with a cough or when I lift something

• heavy. Playing tennis is really a problem – I leak

when I hit the ball – so I pretty much stopped playing”

3 Incontinence Questions (3 IQ)

• 1. During the last 3 months, have you leaked urine, even a small amount?

Yes

• No Questionnaire Completed.
• 2. During the last 3 months, did you leak urine: (Check ALL that apply.)

When you were performing some physical activity such as coughing, sneezing, lifting or exercise? When you had the urge or the feeling that you needed to empty your bladder but you could not get to the toilet fast enough? Without physical activity and without a sense of urgency?

• 3. During the last 3 months, did you leak urine most often: (Check only ONE)

When you were performing some physical activity such as coughing, sneezing, lifting or exercise? When you had the urge or the feeling that you needed to empty your bladder but you could not get to the toilet fast enough? Without physical activity and without a sense of urgency? About equally as often with physical activity as with a sense of urgency?

X X X

And the diagnosis is?

Stress UI Urgency UI Mixed UI Other UI

98% 0% 0% 2%

1.

Stress UI

2.

Urgency UI

3.

Mixed UI

4.

Other UI

Initial Visit & Therapy for UI

• 1. History, Simple Diagnosis - 3 IQ

2.

UA

• 3. Voiding diary
• 4. Patient information

−

Educate and Empower (self-help)

• 5. Treat modifiable factors
• 6. Reasonable expectations

−

Ask patient what she wants!

Urinary Diary

• Simple form for recording voids,

incontinent episodes, fluid intake

• Excellent education & intervention!

− UI episodes by 25-45%

• Very useful in planning therapy

− fluid adjustment − timing and type of medications

National Association For Continence: Patient Resources

• Web site: www.nafc.org

Phone: 1-800-BLADDER

• Diagnostic quiz
• Disease state and

treatment information

• FAQs
• Q&A forum

Behavioral Treatment for UI

Lifestyle changes

• 1. Fluids management
• 2. Avoid Caffeine, carbonated beverages,

alcohol, acidic foods/beverages

• 3. Bedside commode, night light
• 4. Weight loss, diabetes control

Behavioral Treatment for UI

• 5. Pelvic Floor Exercises (“Kegel” exercises)
• Squeeze your bottom like you are trying to hold back gas

(should feel around your vagina as well)

• Hold for 2 seconds and relax for 2 seconds (increase each

by 1 second each week until 10 seconds each)

• 6. Bladder Re-Training
• 7. Bladder control strategies
• Urge control —“Freeze and Squeeze”
• Stress control —“Squeeze before you Sneeze” (lift, etc.)

Verbal and written instructions

Burgio KL. JAMA. 2002;288:2293; Goode PS. JAMA. 2003;290:345; Hay Smith J. In: Abrams P et al. Incontinence. 4th ed. Plymouth, UK: Health Publications, Ltd; 2009

Meta-analysis: PFMT vs. no Rx

• 12 RCT’s with 672 women

− moderate to high risk of bias − variation in interventions used, study populations,

and outcome measures.

• report of cure or improvement with PFMT

− better continence specific quality of life − less leakage on office pad test. − longer training period greater benefit Dumoulin C, Hay-Smith J. Cochrane Database Syst Rev 2010

Patient Information vs. Behavioral Rx

• 222 women with Urge UI: RCT

Improvement

• Self-help booklet

59%

• Verbal/vaginal instruct

69%

• Biofeeback

63% Not statistically different

Bottom line: Educate & Empower!

Burgio KL. JAMA. 2002;288:2293

Bladder Training

• Re-establishing voluntary control
• Schedule voids q 30-60 minutes
• Diary, relaxation, urge suppression
• RCT demonstrated:

− 75% of participants have 50%

improvement Stress and Urge UI

Fantyl 1991

UI Treatment Algorithm

Behavioral Treatment Urgency UI/OAB Medication Stress UI Pessary Surgery

OAB Medications: Patient-Directed Balance

• Relax the bladder
• Symptom relief
• Balance:

OAB Medications

Anticholinergic & Antimuscarinic medications Adverse effects: dry mouth constipation cognitive impairment blurred vision drowsiness headache dizziness Contraindications: narrow angle glaucoma hepatic/renal disease Caution: elderly

Pharmacologic Therapies Indicated for OAB with or without UUI

Nygaard I. N Engl J Med 2010;363:1156-1162 Mirabegron (Myrbetriq, Astellas Pharmaceuticals) 25 or 50 mg by mouth once daily

Mirabegron (Myrbetriq)

• Mirabegron: selective 3-adrenoceptor agonist
• Systematic review and meta-analysis

− Randomized double-blind, placebo-controlled phase III trials − Four publications, N=5,761 patients − No increased risk: htn, arrythmia, retention, discontinuation 2o

AE

Cui Y. Int J Nephrol. 2013

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Cochrane Review OAB Drug Effectiveness

• 61 RCTs; 12,000 adults; 9 meds
• Medication vs. placebo

RR, 95% CI

− Cure or improvement

1.39 (1.28, 1.51)

− UI episodes/dy

0.54 (0.41, 0.67)

− Voids/dy

0.69 (0.54, 0.84)

− Improved QOL − Dry mouth

3.00 (2.70, 3.34)

− No increase in withdrawal

Nabi G et al. Cochrane Database Syst Rev 2006

Antimuscarinic Rx for OAB

• Systematic Review and Meta-Analysis (56 RCTs)
• Tolerability (withdrawals), safety (AEs), efficacy

Chapple et al. Eur Urol 2005 Chapple et al. Eur Urol 2005

• Fewer withdrawals with oxybutynin ER, tolterodine IR and tolterodine

ER vs. oxybutynin IR

• No difference drug vs. placebo except Darifenacin, oxybutynin IR, Propiverine IR
• Excess of any AE with oxybutynin ER (vs. tolterodine IR) and
• xybutynin IR (vs. tolterodine IR and trospium)

Chapple et al. Eur Urol 2005

Antimuscarinic Rx – AE

• Most common AE = dry mouth

−

incidence and severity vs. placebo

−

incidence and severity oxybutynin IR

• Placebo controlled trials

− Blurred vision: oxybutynin IR, solifenacin − Constipation: darifenacin, solifenacin, trospium − Dyspepsia: darifenacin, oxybutynin IR − Erythema and pruritus: oxybutynin TDS − Urinary retention: oxybutynin IR

• Active comparator trials

− Blurred vision: Solifenacin 10 mg/day > tolterodine IR 4 mg/day − Constipation: Oxybutynin IR, tolterodine IR, solifenacin > oxybutynin TDS − Dyspepsia: oxybutynin IR > tolterodine IR

Chapple et al. Eur Urol 2005

Antimuscarinic Rx – Efficacy

• Placebo controlled trials

− ~ all meds better than placebo for: UI episodes, continence,

urgency, voids, volume voided

• Active comparator trials

− UI episodes: oxybutynin ER 10 mg > tolterodine ER 4 mg − Continence: oxybutynin ER 10 mg > tolterodine ER 4 mg − Urgency: solifenacin 5 or 10 mg > tolterodine IR 4 mg − Void frequency: solifenacin 10 mg > tolterodine IR 4 mg

• Quality of Life

− ~ all meds greater improvements in QoL than placebo

Chapple et al. Eur Urol 2005

Behavioral Rx vs. Medications

• 197 women with Urge UI: RCT

UI Placebo 40% Medication 69%+ Biofeedback/behavioral 81%*’

+

* P < 0.05 vs. medication; + P < 0.05 vs. control

• Greater satisfaction in behavioral group

Bottom line: Educate & Empower

Burgio KL et al. JAMA 1998;280:1995-2000

Which Rx First?

• 35 women with Urge UI: modified

crossover extension of RCT UI Behav behav+drug 84% Drug drug+behav 89% Bottom line: Be creative!

Burgio KL et al. J Am Geriatr Soc 2000;4:370-4 2000

BRIDGEs: Diagnose and Treat UUI

• Multicenter, double-blinded, 12-week RCT (N=645)

− Urgency-predominant incontinence, primary care − Diagnosis: 3-item questionnaire − UA − Fesoterodine (4-8 mg daily) or placebo

• Women assigned to Drug had
• UUI episodes/day
• Total episodes/day
• Daytime and nighttime voids
• Urgency
• Safe
• No difference in AE, elevated PVR

Huang AJ et al. Am J Obstet Gynecol. 2012;20:444.e1-11

When to Refer

• Persistent, bothersome symptoms after 2-3 mo trial with

behavioral treatment, drug treatment or both

• Patient not satisfied with treatment outcome
• UTI > 2 in 12 mo, PVR > 200 cc, hematuria, neurological

symptoms, failure to isolate pelvic floor muscles in a patient who desires PFMT, prolapse > hymen

• Refer to a specialist

− Urogynecologist − Urologist − Physical therapist/continence specialist − Continence center

Refractory OAB

Next treatment options:

• Intensive behavioral therapy with biofeedback

– Possible electrical stimulation

• Sacral nerve neuromodulation
• Posterior tibial nerve stimulation
• Botulinum toxin type A injection

Abrams P. Incontinence. 4th ed. Plymouth, UK: Health Publications, Ltd; 2009

Sacral Nerve modulation

• Refractory UUI
• Temporary, percutaneous SN test stimulation

permanent, surgically implanted lead (S3 foramen) and neurostimulator (InterStim, Medtronic)

• In two multicenter trials:

− N=41: 59% had > 50% reduction in UUI/dy (46% dry) at 3 years − N=152: UUI/dy decreased from 10 to 4 at 5 years

• Voids/day decreased and volume voided increased

Siegle SW. Urology. 2000;56:87-91; van Kerrebroeck PE. J Urol. 2007;178:2029-34; Brazzelli M. J Urol, 2006;175:835–41

Sacral Nerve modulation

• Systematic Review, 4 RCT’s, N=120
• Safety: 993 patients, 4 RCT & 20 case control studies
• Reoperation

33%

• Implantable device replaced

15%

• Generator problems

5%

• Electrode/lead problems

16%

• Pain

25%

• Infection, Wound problems

5%

• Adverse bowel function

6% Brazzelli M. J Urol, 2006;175:835–41

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Percutaneous Tibial Nerve Stimulation

• Electrostimulation of the PTN by a fine needle

inserted near the ankle

• Rx for 30 minutes, weekly x 12 weeks
• RCT 220 adults with OAB: PTNS vs. sham

− PTNS had sig. frequency, nocturia, mod/severe

urgency, and UUI episodes vs. sham

• RCT 35 women with UUI PTNS vs. Placebo needle:

− 71% vs. 0% had > 50 reduction in UIEF

Peters KM. J Urol. 2010; Finazzi-Agrò E et al. J Urol. 2010; Moossdorff-

• Steinhauser. Neurourol Urodyn 2013

Intravesical Botulinum Toxin

• Systematic review
• 3 Placebo controlled RCT
• Refractory OAB
• BTX vs. sham had:

− 4 UI episodes/dy

(95% CI: 2, 6)

− QOL − PVR, retention, UTI

Anger JT et al. J Urol 2010;183:2258-64; Cochrane Database Syst Rev 2007

Anticholinergic vs. Botox for UUI

• RCT, 6 mo, N=247

− solifenacin 5-10 mg + intradetrusor saline − Intradetrusor botulinum + Placebo

Visco AG et al. NEJM 2012

Botox Medication P Change in UUI episodes/day

• 3.3
• 3.4

0.81 Resolution UUI 27% 13% 0.003 Dry mouth 31% 46% 0.02 Catheter use (2 mo) 5% 0% 0.01 * ( (

• Visco AG et al. NEJM 2012

Think Outside the Bladder ! UI: Who is at Risk?

Risk Factor Risk Oral estrogen 90% Stroke 90% Diabetes 70% BMI (per 5 units) 60% Poor overall health 60% Hysterectomy 40% COPD 40% Age (per 5 years) 30% Live birth 30%

Brown JS et al. Obstet Gynecol 1996;87:715-21

UI: Who is at Risk?

Risk Factor Risk Oral estrogen 90% Stroke 90% Diabetes 70% BMI (per 5 units) 60% Poor overall health 60% Hysterectomy 40% COPD 40% Age (per 5 years) 30% Live birth 30%

Brown JS et al. Obstet Gynecol 1996;87:715-21

Estrogen Therapy for UI

• UI with estrogen Rx in observational studies

− Receptors in urethra, bladder

• 7 RCTs oral CEE/MPA vs. placebo (N=15,593)

− HERS & WHI

• For Stress, Urge, & Mixed UI:

− Prevalent UI: frequency 40 - 50% (4 mo 4 yrs) − Incident UI at 1 yr: 15% to 2 -fold

Bottom line: oral HT not for prevention or Rx of UI

Grady DG. Obstet Gynecol 2001; Hendrix SL. JAMA 2005;293:935-48

Weight Reduction & UI

• In women about 200 lbs:

Weight loss: > 5% or 30 lbs > 50% in incontinence episodes

• Effective therapy for UI
• Unique motivator for weight loss
• Public Health Implications

Subak 2002; Subak 2006

Weight Reduction & UI

Program to Reduce Incontinence by Diet & Exercise

− NIDDK-funded RCT 338 obese women with UI − 6-month lifestyle intervention vs. control

Intervention Control P-Value Weight

• 8.2%
• 1.8%

<0.0001 Total UI

• 46%
• 25%

0.04 Weight Loss similar to medications…

Subak LL et al. N Engl J Med. 2009;360:481-90

DM: Independent Risk Factor for UI

• 1.5 million women with Type 2 DM have UI
• DM associated with:

− 2-fold in UI prevalence & incidence

− UI severity − bother, QOL impact

If DM prevented, eliminate 17% of UI and 50% of severe UI

• Women with pre-diabetes: similar findings!

Nurses Health Study (Lifford 2005); NHANES 2001-2 (Brown 2006); Brown 1999; Ebbesen 2007

Diabetes Prevention Trial

DPP Lifestyle N = 1,079 Placebo N = 1,082 Metformin N = 1,073

• Knowler. NEJM 2002; Brown JS. Diabetes Care 2005

UI: 38%* UI: 48% UI: 46%

DPP UI Summary

Among women with pre-diabetes:

• Weight loss and exercise: UI
• Weight change accounted for treatment effect

DPP-Outcomes Study:

• Long-term effects for prevention and early disease

Brown JS. Diabetes Care 2006

UI Treatment Effectiveness

• Placebo

20-40%

• Behavioral

40-80%

• Pharmacological

40-70%

− Side effects, discontinuation 50%

• Weight Loss

50-60%

• Surgery

80-100%

− Long-term cure

50%

Non-surgical treatments similar!

Summary and Conclusion

Incontinence is common and treatable

• Simple diagnosis: 3IQ and UA
• Simple treatments: Info ± Rx
• Ask patient what she wants!
• Combine treatments, flexibility
• Refer if no improvement in 2–6 months

Educate and Empower!

www.ucsf.edu/wcc