Evaluation of Edward Hines, Jr. VA Hospital

8/10/2010

1

Evaluation of Appropriateness/Inappropriateness of

Medication Prescribing Using the STOPP/START Criteria in Home Based

Primary Care Veterans

Millie Brahmbhatt, Pharm.D.Pharmacy Practice Resident

Edward Hines, Jr. VA HospitalNo conflict of interest to disclose

Edward Hines, Jr. VA Hospital• 12 miles west of

downtown Chicago• Tertiary care referral

center• 483 beds• Serves ~54,000

veterans• Associated with

Loyola University –Stritch School of Medicine

Learning Objectives• Discuss inappropriate medication

prescribing in elderly patients.

• Identify medications with a potentialIdentify medications with a potential benefit in the elderly population.

• Discuss the use of STOPP/START criteria in elderly Home Based Primary Care Veterans.

Inappropriate Medications in Elderly Population1,2

• Increased risk for adverse drug events• Adverse drug events responsible for 30%

of hospital admissionsp• Physiologic changes can alter

pharmacokinetic/pharmacodynamic properties

• Often denied potentially beneficial medications

Tools to Assess Inappropriate Prescribing1

Beers’ Criteria

Improved Prescribing in the Elderly Tool (IPET)(IPET)

Medication Appropriateness Index (MAI)

Assessing Care of Vulnerable Elders (ACOVE)

Screening Tool of Older People’s potentially inappropriate

Prescriptions(STOPP)/Screening Tool to Alert doctors to Right Treatments (START) Criteria1

• STOPP: 65 clinically significant criteria for potentially inappropriate medication use

• START: 22 evidence based prescribing indicators for commonly encountered disease states

8/10/2010

2

STOPP Criteria1

• 10 categories include:– Cardiovascular system (17)– Central nervous system and psychotropic drugs

(13)– Gastrointestinal system (5)

•Aspirin > 150 mg/dayMostly related to TricyclicAntidepressant usePPI for peptic ulcer disease at full

therapeutic dosage for >8 weeks

Systemic corticosteroids

instead of inhaled corticosteroids for

COPD

Mostly related to NSAID use

– Respiratory system (3)– Musculoskeletal system (8)– Urogenital system (6)– Endocrine system (4)– Drugs that adversely affect fallers (5)– Analgesic drugs (3)– Duplicate drug classes (1)

COPD

Mostly identified misuse with

antimuscarinic drugsΒ-Blockers in DM and frequent hypoglycemic

episodes

•Benzodiazepines•Neuroleptics

•1st generation antihistamines•Vasodilators

•Long-term opiatesRegular opiates for more than 2 weeks in those

with chronic constipation without a laxativeIdentify any duplicate

drug class prescription

START Criteria1

• 6 categories include:– Cardiovascular system (8)– Respiratory system (3)

ACE-I in CHFRegular inhaled β2

agonist or anticholinergic for asthma or COPD

Antidepressant with moderate/severep y y ( )

– Central nervous system (2)– Gastrointestinal system (2)– Musculoskeletal system (3)– Endocrine system (4)

asthma or COPDmoderate/severe depressive symptoms

lasting at least 3 monthsPPI with severe GERD

or peptic stricture requiring dilationCalcium and vitamin

D in patients with known osteoporosisAntiplatelet therapy in

DM with coexisting major CV risk factors

Self Assessment Question #1

The STOPP criteria identify aspirin > 150 mg/day as potentially inappropriate.

A. TrueB. False

Self Assessment Question #2

Which medication class affecting the central nervous system is identified most frequently in the STOPP criteria?

A. BenzodiazepinesB. Selective Serotonin Re-uptake InhibitorsC. Tricyclic AntidepressantsD. Neuroleptics

Previous Trials• Gallagher et al.3

– Objective: To compare the performance of the STOPP criteria to the Beers’ criteria

– Methods: Prospective study of 715 acute admissionsResults: STOPP identified 336 potentially inappropriate– Results: STOPP identified 336 potentially inappropriate medications, Beers’ criteria identified 226 potentially inappropriate medications

– Conclusion: Significant difference in the number of potentially inappropriate medications detected by the STOPP criteria than Beers’ criteria

Previous Trials• Davis et al.4

– Objective: To examine medication appropriateness using MAI and recommendation acceptance associated with pharmacist medication review for veterans enrolled in the home based primary care programp y p g

– Methods: Retrospective analysis– Results: Statistically significant decrease in MAI score

from initial review to end of study– Conclusion: By use of MAI for evaluation, pharmacist

recommendations significantly improved appropriateness of medication use

8/10/2010

3

Home Based Primary Care (HBPC) Program

• Provides primary care and outpatient monitoring to patients who are home bound

• Interdisciplinary team approach• Interdisciplinary team approach• HBPC team reviews each patient within 14

days of admission and every 90 days thereafter

• Pharmacists conduct an evaluation of a patient’s medication regimen initially and every 90 days thereafter

Study Purpose

Evaluate appropriateness/inappropriateness of medication prescribing using the STOPP/START criteria in elderly HBPC veterans and understand th t ti l i t f th HBPC t ththe potential impact of the HBPC team on the STOPP/START criteria.

Study Design• Retrospective chart review of patients

enrolled in HBPC program from 9/1/07 to 9/30/09

• Patients reviewed using Computerized Patient Record System (CPRS)

• Approved by Institutional Review Board

Study Design: Primary Outcome• Appropriateness/inappropriateness of

medication prescribing using STOPP/START criteria– Evaluated by comparing medication list at the

initial pharmacist note for medications that metinitial pharmacist note for medications that met STOPP/START criteria to medication list at follow up note that occurred within 15 weeks

– Assigning each patient STOPP score and START score

– Identifying patients with a 2 point improvement in STOPP or START score

• Impact of HBPC team on STOPP/START criteria– Assessed by examining the number and type

of pharmacist recommendations made and accepted regarding:

Study Design: Secondary Outcome

accepted regarding:• Medications discontinued• Medications started• Medications renewed• Dosage adjustments• Drug-drug interactions• Drug-disease interactions• Monitoring of lab values

STOPP and START Scoring

• “1” assigned for an active prescription• “0” assigned in the absence of an active

prescriptionp p• STOPP: Higher score indicates more

inappropriate medications• START: Higher score indicates more

appropriate medications

8/10/2010

4

Study Design

• Inclusion Criteria– Enrolled in HBPC

program– 65 years or older

• Exclusion Criteria– Admission to hospital

between initial review and follow up reviewy

– Initial review and follow up review within 15 weeks

– Admission to HBPC for palliative or hospice care

– Death prior to completion of second medication review

Data Collected• Demographic information: age, gender, race

• Medication dosages and duration of therapy

• Pharmacist recommendations:– Number of recommendations made and accepted

• Medications discontinued• Medications started• Medications renewed• Dosage adjustments• Drug-drug interactions• Drug-disease interactions• Monitoring of lab values

Statistical Analysis• Baseline characteristics described using counts and

percentages for categorical variables and means and standard deviations for continuous variables

• Average STOPP and START score calculated at initial review and compared to follow up score

• Baseline values compared to follow up values using a• Baseline values compared to follow up values using a paired t-test

• Average number of recommendations made and accepted compared between patients with a 2 point change in STOPP or START score

• Estimated 200 patients required to detect a small effect size of 0.2 with 80% power and alpha of 0.05

Results: Enrollment

311 Charts Reviewed

200 patients 111 patients included excluded

Admission to hospital (n=48)

Age <65 years

(n=40)

Death (n=14)

No follow up note within 15

weeks (n=5)

Palliative or hospice care

(n=2)

Results: Baseline Characteristics

• Age– Average age 82.4 years

• Gender96% male– 96% male

• Race– 61.5% Caucasian– 23% African American– 2% Asian– 0.5% Hispanic– 13% unknown/unanswered

Results: Primary Outcome

Initial Follow-up p-valueSTOPP 1.2 0.895 0.0014START 3.3 3.33 0.5720

Change in STOPP score and START score

Improvement by at least 2 points

# of patients

Average # of Pharm.D.

recommendations in patients with improved score

Average # of Pharm.D.

recommendations in patients without

2 point improvement

p-value

STOPP 15 10.5 5.7 <0.001

START 8 5.1 3.2 0.014

8/10/2010

5

Results: Secondary OutcomeAverage number of type of pharmacist recommendations

made and accepted

Study Conclusion: Primary Outcome

• Statistically significant improvement in STOPP score

• Change in START score not found to be statistically significantsignificant

• Patients with at least a 2 point improvement in STOPP or START score had statistically significant greater number of pharmacist recommendations made; however, no difference in number of recommendations accepted

Study Conclusion: Secondary Outcome

• Greatest number of pharmacist recommendations made regarding:– Monitoring of lab values– Discontinuing medications– Adjusting dose

Limitations

• Retrospective chart review

• Majority of population Caucasian maleMajority of population Caucasian male

• Short duration of 15 weeks

• Some STOPP/START criteria not clearly defined

Future Direction

• Educate HBPC team to identify commonly encountered STOPP/START criteria to improve medication prescribing

• Evaluation of cost savings associated with recommendations made by HBPC pharmacists and accepted by HBPC team

Acknowledgments

• Kavita Palla, Pharm.D., BCPS (Principal Investigator)• Liancy Gomez, Pharm.D., CGP, BCPS (Co-Investigator)• Annette Kossifologos, Pharm.D., BCPS (Co-Investigator)• Todd Lee Ph D Pharm D (Co Investigator)• Todd Lee, Ph.D., Pharm.D. (Co-Investigator)• Dayna Mitchell, Pharm.D., BCPS (Co-Investigator)

8/10/2010

6

References1. Gallagher P, Ryan C, Byrne S, et al. STOPP (Screening Tool of Older Person’s

Prescriptions) and START (Screening Tool to Alert doctors to Right Treatment). Consensus validation. International Journal of Clinical Pharmacology and Therapeutics. 2008; 46(2):72-83.

2. Lazarou J, Pomeranz BH, Corey PN. Incidence of Adverse Drug Reactions in Hospitalized Patients: a Meta-Analysis of Prospective Studies. Journal of the American Medical Association. 1998; 279:1200-5.American Medical Association. 1998; 279:1200 5.

3. Gallagher P, O’Mahony D. STOPP (Screening Tool of Older Persons’ potentially inappropriate Prescriptions): Application to Acutely Ill Elderly Patients and Comparison with Beers’ Criteria. Age and Ageing. 2008; 37:673-679.

4. Davis RG, Hepfinger CA, Sauer KA, et al. Retrospective Evaluation of Medication Appropriateness and Clinical Pharmacist Drug Therapy Recommendations for Home-Based Primary Care Veterans. The American Journal of Geriatric Pharmacotherapy. 2007; 5(1):40-7.

Questions

1

Establishing Pharmacist-Managed Ambulatory Care Services within a Clinical

Cancer CenterJustin B. Guthman, PharmD

PGY2 Health-System Administrative ResidentFroedtert Hospital

Milwaukee, WisconsinAugust 2010

Conflict of Interest

• No conflicts of interest to disclose

Objectives

• Discuss why the Breast Care Center (BCC) at Froedtert Hospital (FH) was the pilot site for implementing pharmacist-managed ambulatory care servicesmanaged ambulatory care services

• Identify the role of pharmacist-managed ambulatory care services within a cancer center

Overview of Presentation

• Background• Project Purpose• Breast Care Center Workflow• Results • Justification• Conclusion

Froedtert Hospital Clinical Cancer Center

2

HUB model

• Specialized oncology lab• Clinics separated by disease state

– Courage– Life – Hope – Faith – Breast Care Center

• Day hospital infusion center• Radiology Oncology• Retail Oncology Pharmacy

• To assess the need for pharmacist-managed ambulatory care services within a clinical cancer center

Project Purpose

At your organization are there pharmacists within the oncology

clinics that provide direct patient care?

1. Yes1. Yes2. No3. Unknown

Breast Care Center at Froedtert Hospital

• Favorable site for piloting pharmacist-managed ambulatory care services– Patient need– Staff acceptanceStaff acceptance– Patient volume

• Provides care to over 265 patients each week

Breast Care Center Staff Survey

• A pharmacist located in the BCC would improve the quality of patient care

• A pharmacist located in the BCC would save me valuable time

11 of 11 respondents agreed

9 f 11 d t d• A pharmacist located in the BCC would improve

patient satisfaction

• Overall, a pharmacist would be a valuable addition to the BCC




Breast Care Center Work Flow•Shadow oncology staff members

•Physicians, mid-level practitioners, nurses, and medical assistants•Evaluate potential role for pharmacist interaction

•Build relationships and trust with oncology staff•Provide quick and accurate information to medication•Provide quick and accurate information to medication questions

•Develop intervention tracking tool for categorization•Supportive•Treatment •Financial

3

Intervention Tracking Tool Pharmacist Typical Day

• 0700-0830– Evaluate scheduled

patients

• 0830-1200 (AM Oncologist)( g )– Visit with select patients

• 1200-1600 (PM Oncologist)– Visit with select patients

Intervention Results(n=139)

Financial12%Treatment

26%

Supportive61%

Supportive Care Intervention Results (n=86)

Supportive61%

Supportive Care Intervention Results (n=86)

Patient

Physician

0 5 10 15 20 25 30 35 40 45

Education Tool

Mid-Level

Nursing

Number of Interventions

Supportive Care

Side effects20%Other

Physician Interventions(n=40)

Antiemetic10%

Narcotic15%

Dosing15%

20%25%

Interactions15%

4

Supportive Care

Other21%

Patient Interventions(n=24)

Bone Health50%

Compliance29%

21%

Staff Education ToolsMedical Management of Hot Flashes

Medication Dose Effectiveness Time Frame Side Effects

Venlafaxine(Effexor®)

37.5 mg qAM titrate to max of

75 mg

25-42% decrease in symptoms

1-2 weeks but may take 4-8 weeks for full

Decreased appetite, anxiety,

constipation,geffects

p ,dry mouth, and

nausea

Paroxetine (Paxil®)

*AVOID WITH TAMOXIFEN*

10-12.5 mg daily titrate to 25 mg


1-2 weeks but may take 4-8 weeks for full

effects

Headache, nausea,

somnolence, insomnia, and

dry mouth

Gabapentin(Neurontin®)

300 mg at bedtime titrate

up to 900 mg (in divided doses)

as needed


May take 2-3 weeks for full

effects

Somnolence, fatigue,

dizziness, rash

Treatment26%

Treatment Intervention Results (n=36) Treatment Intervention Results

(n=36)

Patient

Physician

0 5 10 15 20 25 30

Mid-Level

Nursing

Patient


Other13%

ADR

Treatment Interventions

Physician Interventions (n=24)

Management13%

Efficiency Enhancements

33%

Interactions41%

Financial Intervention Results (n=16)

Financial12%

5

Financial Interventions (n=16)

New prescriptions sent tooutpatient pharmacy

0 1 2 3 4 5 6 7 8

Education about coverage

Completion of PriorAuthorization


Justification and Financial Impact• Customer Service (Patients and Medical Staff)

– Assisted medical team with dosing, side effect management/prevention, and educational updates

– Avoided drug interactions– Promoted compliance and osteoporosis prevention

• Revenue– A 30% increase in the use of the outpatient pharmacy

during 12 week pilot ($10,384)– Prescription delivered to patients while receiving

chemotherapy infusion ($2,440)– Combined nursing-pharmacist facility charge

Future Directions• A business plan was proposed to Froedtert

Hospital management which resulted in the expansion of ambulatory pharmacy services

• Continued expansion of combined nursing and pharmacist billingpharmacist billing

• Evaluate the need for a collaborative practice agreement to expand pharmacists role

• Explore other areas of the Clinical Cancer Center for expand pharmacy services

Conclusions

• Pharmacist-managed ambulatory care services within the BCC at Froedtert Hospital have been favorable

Provider/Staff satisfaction– Provider/Staff satisfaction– Documented interventions– Informal patient satisfaction

Acknowledgements

• Angela Urmanski, PharmD, BCOP– Investigational Drug / Hematology - Oncology Pharmacist

• Binita Patel-Naik, PharmD, MS – Assistant Pharmacy Director - Ambulatory Care y y

• Erika Smith, PharmD– Retail/Ambulatory Supervisor

• Melissa Theesfeld, PharmD – Assistant Director of Experiential Education - Concordia

University of Wisconsin

Contact Information

Justin B. Guthman, PharmDPGY2 Health-System Administrative ResidentPGY2 Health System Administrative ResidentFroedtert Hospital9200 West Wisconsin AvenueMilwaukee, Wisconsin [email protected]

1

Incidence and Management of Arthralgias in Breast Cancer

Patients Treated with Aromatase Inhibitors in an Outpatient

Oncology Clinic

Pamela Menas, PharmD

• Describe the role of aromatase inhibitors (AIs) in the treatment of breast cancer

• Describe the incidence and impact of

Objectives

pAI-induced arthralgias

• Discuss the management of AI-induced arthralgias in breast cancer patients

I HAVE NO CONFLICTS OF INTEREST TO REPORT

Study Location• Kellogg Cancer Centers (KCC)

−Established in 1981−One of the first National Cancer Institute (NCI)

Community Clinical Oncology Programs (1983)• Three locations• Three locations

−Evanston, IL−Glenview, IL−Highland Park, IL

• Average number of patients treated per month: 1100

Breast Cancer• Most common type of cancer in

women in US • More than 2.5 million breast cancer

survivors nation-wide1

• 192,370 new cases per year• 40,170 deaths per year• 2nd most common cause of cancer-

related deaths among women in US1

• Approximately 75% of breast cancers are hormone receptor (+)2

• Postmenopausal women synthesize estrogen in adipose, muscle and

Breast Cancer

breast tissue 2• Aromatase enzyme converts

androgens to estrogen 2• AIs inhibit estrogen synthesis by

blocking this conversion 2

Aromatase Inhibitors (AIs)

• First line adjuvant treatment in post-menopausal women with hormone receptor (+) tumors3,4

R d d l th f t t t• Recommended length of treatment:5 years3,4

2

AI Adverse Effects

• Hot flashes• Insomnia• Fatigue• Osteoporosis• Arthralgias

AI-Induced Arthralgias• A common side effect of AI therapy• Frequently cited as the primary

reason for lack of compliance5,9

• Affected joints: wrists, hands, knees,Affected joints: wrists, hands, knees, back, ankles, and feet7

• Few management strategies proposed in literature

• No standard treatment algorithm in place at Kellogg Cancer Center (KCC)

• Evaluate incidence and management of AI-induced arthralgias in the outpatient oncology clinic at KCC

• Develop a treatment algorithm and

Study Purpose

Develop a treatment algorithm and electronic medical record (EMR) documentation tools

Methods

• Retrospective EMR review of 206 patients seen for follow up at KCC from 7/09 through 10/09

• IRB approved

• Inclusion Criteria:−Postmenopausal women with stage I-III

hormone receptor positive breast cancer currently taking or have taken AI therapy

Methods

• Exclusion Criteria:−Pre-existing rheumatoid arthritis−Metastatic disease

• Definition of postmenopausal:−Prior bilateral oophorectomy OR−Amenorrhea for 1 year with intact uterus

and ovaries OR

Methods

and ovaries OR−Serum estradiol and FSH levels

commensurate with menopause for =>6mos

3

• Data Collected:−Age−Weight −Length of AI therapy

Methods

Length of AI therapy−Co-morbidities−Medication history−Reports of arthralgias−Arthralgia management

• Primary Endpoints:−Assess overall incidence of AI-induced

arthralgias at KCC−Evaluate management of AI-induced

Methods

garthralgias

• Statistical Analysis:−Chi square and binomial two-sided exact

test for descriptive statistics−Two-sample independent t-test for

Methods

p pcontinuous variables

−A p-value <0.05 was considered statistically significant

• AI-induced arthralgias in KCC patients occurred at a rate of 48% which was similar to those reported in literature (40%)5,6,7

Results

• Patients who reported arthralgias were younger than patients who did not report arthralgias (61 vs. 65 years, p=0.002)

• Incidence of arthralgias same among all AIs: anastrozole, exemestane and l t l ( 0 729)

Results

letrozole (p=0.729)

• 32% documented as having arthralgias within the 1st 6 months of therapy

Results

−Literature suggests arthralgias occur in first year of AI therapy with 60% presenting within 1st 6 months of treatment6,8, 10,11

4

• No difference in incidence of arthralgias in patients who received chemotherapy compared to those who did not (p=0 352)

Results

who did not (p=0.352)

− In literature, chemotherapy sited as common cause of arthralgias, potentially making it difficult to determine cause in patients receiving both

• Of patients with AI-induced arthralgias, 88% were managed without AI therapy alteration

Results

• 41% of patients presenting with arthralgias did not have documentation of arthralgia management in EMR

• A treatment algorithm based on treatments for arthralgias found in literature and KCC physician experience

Treatment Algorithm

experience

Initial AI treatment

Assess presence of AI arthralgias

YES NOYES NO

Pain scale0-10

to determine severity

YES NO

Immediate response needed?

May use Omega-3 fatty acids and OTC pain reliever together if immediate

response needed

Fish oil/Omega-3 fatty acids1000mg BID

Glucosamine sulfate500mg TID

No relief within 2 weeks:No relief within 2 weeks:OTC pain reliever

Ibuprofen 200-400mg Q4-6h prnNaproxen 220mg Q8-12h prn

Acetaminophen 500mg Q6h prn

5

No relief within 2 weeks:Discontinue OTC pain relievers

Add COX-2 inhibitorOR

Rx NSAIDsOR

Change to another AI therapyChange to another AI therapy

No relief within 2 weeks:Discontinue Rx NSAIDs

Add opioid

Documentation Tool

Documentation Tool Documentation Tool

Documentation Tool Documentation Tool

6

Documentation Tool

*Based on Common Terminology Criteria for Adverse Events (CTCAE) V 3.012

**

Documentation Tool

Documentation Tool• Douglas Merkel, MD• Elaine Wade, MD• Leon Dragon, MD• Margaret Whalen, RN• Hongyan Du MS

Acknowledgements

Hongyan Du, MS• Wendy Hui, PharmD, BCOP• Jessica Lawton, PharmD, BCOP• Abigail Harper, PharmD, BCOP• Amanda Blankenship, PharmD• George Carro, RPh, MS, BCOP

References1. AmericanCancerSociety. How Many Women Get Breast Cancer? http://www.cancer.org

Accessed 9/29/09.2. WebMD. Types of Breast Cancer: ER Positive, HER2 Positive, and Triple Negative.

http://www.webmd.com/breast-cancer/breast-cancer-types-er-positive-her2-positive. Accessed4/13/10.

3. Safety of adjuvant endocrine therapies in hormone receptor-positive early breast cancer. S.Sehdev, et al. Curr Oncol 2009; vol 16; supp 2.

4. Perspective Study to Assess Short-Term Intra-Articular and Tenosynovial Changes in theAromatase Inhibitor-Associated Arthralgia Syndrome. Morales, L et al. J Clin Oncol 2008;26:3147-3152.

5. Aromatase inhibitor-induced arthralgia: Clinical experience and treatment recommendation. R. E.gColeman, et al. Cancer Treatment Reviews (2008) 34, 275-282.

6. Getting a Grip on Aromatase Inhibitor-Associated Arthralgias. Hershman, D. J Clin Oncol 2008;26: 3120-3121.

7. Patterns and Risk Factors Associated With Aromatase Inhibitor-Related Arthralgia Among BreastCancer Survivors. Mao, J et al. Cancer 2009; 115: 3631-3639.

8. Prevalence of Joint Symptoms in Post menopausal Women Taking Aromatase Inhibitors for Early-Stage Breast Cancer. Crew, K et al. J Clin Oncol 2007; 25:3877-3883.

9. Risk factors for joint symptoms in patients enrolled in the ATAC trial: a retrospective, exploratoryanalysis. Sestak, I et al. Lancet Oncol 2008; 9: 866-872.

10. Anastrozole alone or in combination with tamoxifen versus tamoxifen alone for adjuvant treatmentof post menopausal women with early breast cancer: first results of the ATAC randomized trial.The ATAC Trialists’ Group. The Lancet 2002; vol 349; issue 9324: 2131-2139.

11. Treatment-emergent endocrine symptoms and the risk of breast cancer recurrence: a retrospectiveanalysis of the ATAC trial. Cuzick, J et al. Lancet Oncol 2008; 9: 1143-1148.

12. Common Terminology Criteria for Adverse Events (CTCAE) v 3.0. National Institutes of Health,National Cancer Institute

Self-Assessment Question:Aromatase inhibitors are indicated for

which types of patients with breast cancer?

A. Premenopausal women with early stage didisease

B. Premenopausal women with hormone receptor positive disease

C. Postmenopausal women with hormone receptor negative disease

D. Postmenopausal women with hormone receptor positive disease

7

Which statement regarding AI-induced arthralgias is TRUE?

A. AI-induced arthralgias never interfere with AI therapy

Self-Assessment Question:

B. AI-induced arthralgias are highly uncommon

C. AI-induced arthralgias are the most frequently cited reason for discontinuation of AI therapy

D. There is a “gold standard” for treatment for AI-induced arthralgias

Questions???

ICHP Annual Meeting 2010 Menas – Residency Pearls: Arthralgias in Breast Cancer Patients 121-000-10-056-L01-P

Post Test Questions

1. Aromatase inhibitors are indicated for which types of patients with breast cancer?

A. Premenopausal women with early stage disease

B. Premenopausal women with hormone receptor positive disease

C. Postmenopausal women with hormone receptor negative disease

D. Postmenopausal women with hormone receptor positive disease

2. Which statement regarding AI‐induced arthralgias is TRUE?

A. AI‐induced arthralgias never interfere with AI therapy

B. AI‐induced arthralgias are highly uncommon

C. AI‐induced arthralgias are the most frequently cited reason for discontinuation of AI therapy

D. There is a “gold standard” for treatment for AI‐induced arthralgias

3. Of patients presenting with arthralgias, which percent did not have documentation of arthralgia management in EMR?

A. 14%

B. 34%

C. 57%

D. 41%

8/10/2010

1

Heart Failure Exacerbation Caused by Serotonin-Norepinephrine

Reuptake Inhibitors in a Veteran Population

Kelly L. Perez, Pharm.D.Jesse Brown VA Medical

Center28 August 2010

The speaker has no conflict to disclose in relation to this program.

Learning Objectives

• Recognize modifiable risk factors that may cause heart failure (HF) exacerbation

• Define the proposed mechanism by which serotonin-norepinephrine reuptake inhibitors (SNRIs) may exacerbate HF

Outline

• Review the incidence, socioeconomic burden, and etiology of HF in the United States

• Discuss depression in patients with HF

Di th d h i f SNRI• Discuss the proposed mechanism of SNRI-induced HF

• Introduce purpose and methods

• Review study results

• Discuss conclusions

• Address limitations and future directions

Epidemiology of Heart Failure• Growing problem in the United States

o Affects about 5 million individuals

• > 550,000 new cases annually

• Incidence ~10 per 1000 individuals over age 65

• > 1.1 million hospitalizations in 2006o Estimated total cost of $37.2 billion for 2009o 1/8 deaths mention HF on the death certificate

Hunt SA, et al. Circulation 2009;119:e391-e479.Lloyd-Jones D, et al. Circulation 2009;119:e21-e181.

Etiology of Heart FailureDisease State Progression

• Hypertension (HTN)• Coronary artery disease

(CAD)

Medication-Induced

• Anthracyclines• Non-steroidal anti-

inflammatory drugs (NSAIDs)

• Valvular heart disease• Diabetes mellitus (DM)• Cardiomyopathy

• Thiazolidinediones• Interferons & interleukin-2• Glucocorticoids• Antipsychotics• Antimigraine drugs• Antifungals• Antidepressants

Slordal L, et al. Drug Safety 2006;29:567-586.

Depression in Heart Failure• Common comorbidity

• Associated with poor prognosis and increased mortality

• Incidence ranges from 13.9-36.5%, possibly as high as 77%

• 2005 Cochrane review found no randomized clinical trials studying psychological interventions in HF patients

Jiang W, et al. Arch Intern Med 2001;161:1849-56.Thomas SA, et al. AACN Clin Issues 2003;14:3-12. Lane DA, et al. Cochrane Database Syst Rev 2005;1: CD003329.

8/10/2010

2

Antidepressant Use in Heart Failure

• No randomized clinical trials or practice guidelines to guide therapy

• Few studies evaluate the use of antidepressants in HFo Older agents limited to a short duration of therapyo Little information available on selective serotonin reuptake inhibitors

(SSRIs) and SRNIs(SSRIs) and SRNIs

• Adverse cardiac events of antidepressants: orthostatic hypotension, HTN, conduction abnormalities

• Published case reports demonstrating exacerbation or development of HF after SNRI initiation

Slordal L, et al. Drug Safety 2006;29:567-586.Alvarez W, et al. Pharmacotherapy 2003;23:754-71.

Colucci, et al. • Case 1: 39 yo female with stable HF

prescribed venlafaxine 75 mg BIDo Presented with increasing dyspnea, fluid retention,

ejection fraction (EF) of 15%

o Fatigued and tachycardic for 3 months post-discharge with EF of 25-30% until venlafaxine gdiscontinued

o 2 weeks later her symptoms fully resolved; however, mood worsened

o Prescribed duloxetine, but cardiac symptoms resumed

o Duloxetine was discontinued and sertraline was substituted which resulted in stabilization of all her symptoms

Colucci VJ, et al. Ann Pharmacother 2008;42:882-7.

Colucci, et al. • Case 2: 68 yo male with NYHA Class IV HF (stable

EF ~25%) on duloxetine 30 mg QD x 1 week, then 60 mg QD x 1 additional week for DM neuropathy

o Presented with tachycardia, orthopnea, dyspnea, 3.6 kg weight gaing g

o Diuresed and duloxetine was discontinuedo Lost 3.2 kg, HR normalized, and symptom resolution

within 2 days

• Authors attributed increased serum norepinephrine(NE), which may negate the effects of sympatholytics, to both patients’ worsening HF

Colucci VJ, et al. Ann Pharmacother 2008;42:882-7.

Drent, et al. • Case 1: 21 yo previously healthy female

on venlafaxine 35 mg daily x 1 month, then 75 mg daily x 1 additional month

o Presented with progressive dyspnea, cough, vomiting, 15 kg weight loss, syncope x 4

kweekso Reduced EF reported, but data not provided o Treated with corticosteroids x 10 days

without improvement, then venlafaxine was discontinued

o Full resolution of clinical condition within 2 weeks

Drent M, et al. Am j Respir Crit Care Med 2003;167:958-61.

Drent, et al. • Case 2: 62 yo male with ischemic heart

disease, on unspecified dose of venlafaxine x 1 month

o Presented with exertional dyspnea, dry cough, fever o Venlafaxine discontinued during admissiono Reduced EF reported, but data not providedo Patient’s condition complicated by lung cancer ando Patient s condition complicated by lung cancer and

worsened until he expired

• Authors believe both patients suffered from SNRI-induced noneosinophilic interstitial pneumonia and cardiac failure

o Proposed mechanism: reduced cytochrome P450 metabolism of the drug by genetic polymorphisms causing toxic effects

Drent M, et al. Am J Respir Crit Care Med 2003;167:958-61.

Proposed Mechanism of SNRI-Induced HF and Exacerbation

• Mediated by increasing NE, secondary to inhibition of reuptake in the neuronal synapse

• Causes an increase in sympathetic nervous system activity

• Based on the neurohormonal model of HF• Based on the neurohormonal model of HF, sympathetic activation causes:

o Sodium and water retentiono Increases in both preload and afterloado Decline in left ventricular function

• Pharmacologic increase in NE, like those caused by SNRIs, has the potential to exacerbate HF

Hasking GJ, et al. Circulation 1986;73:615-21. Bleske BE. Pharmacotherapy 2000;20:349S-58S.

8/10/2010

3

Norepinephrine-Serotonin Affinity

Drug Norepinephrine:Serotonin AffinityRatio*

Duloxetine 7.23

Venlafaxine 116

Citalopram 3696

* Based on Ki (inhibitory constant); the smaller the ratio the greater the affinity/inhibition

Baldessarini, RJ. Pharmacological Basis of Therapeutics. 11th ed, 2006.

Purpose

• To evaluate the incidence of HF exacerbations in patients receiving a SNRI, either venlafaxine or duloxetine, compared to the SSRI citalopramcompared to the SSRI citalopram

Methodology • Retrospective, electronic chart review of HF

exacerbations at Jesse Brown VA Medical Center (JBVAMC)

• IRB and VA Research and Development Committee approved

• List generated from available databases• All indications for SNRI use were included in the study• Exacerbation of HF includes any documentation by

the patient’s provider in the electronic chart using terminology suggesting worsening HF

Methodology

• Inclusion criteriao ≥ 18 years of ageo From 1 Oct 06 to 15 Sept 09:

ICD-9 diagnosis of HFPrescription for venlafaxine, duloxetine, or citalopram

• Exclusion criteriao None

MethodologyData Collection

• Demographic informationo Ageo Gendero Ethnicityo Baseline information

• Event datao Weighto EF

• Date of HF diagnosiso Type of HF

Blood pressure (BP) prior to SNRI initiationWeightBody mass index (BMI)EF

o Type of HFo Date(s) of exacerbation(s)

• Antidepressant informationo Agent o Dose at time of

exacerbationo Date of initiationo Indication

MethodologyData Collection

• Co-morbiditieso A fib/a flutter o HTNo CKDo Anemia

• Recommended HF therapieso ACE inhibitors/ARBso Beta adrenergic

antagonists

o Hyper-/hypo-thyroidismo DM

• Social history

o Diureticso Aldosterone antagonistso Hydralazine + nitrateso Digoxin

• Medications that may worsen HF

8/10/2010

4

Statistical Analysis

• Student’s t-test for continuous data

• Chi-square test for nominal data

• Alpha was set at 0.05 for a power of 80%

Endpoints

• Primaryo Incidence of HF exacerbation in patients receiving a

SNRI versus patients receiving citalopram

• SecondarySecondaryo Time to HF event post-SNRI initiation o To determine if a difference exists in severity of HF

exacerbation (either treated as an outpatient or requiring hospitalization) between treatment groups

Study PopulationMet Entry Criteria

(293)

V l f i D l ti HF +Venlafaxine(n = 29)

Duloxetine(n = 0)

HF Citalopram(n = 264)

Citalopram(n = 34)

Randomly Selected

N = 63


Characteristic Venlafaxine(n = 29)

Citalopram(n = 34) p-value

Mean age, years (SD) 62.7 (9.4) 68.4 (12.7) 0.05Gender, n (%)

Male 29 (100.0) 34 (100.0)> 0.99

Female 0 (0.0) 0 (0.0)R /Eth i it (%)Race/Ethnicity, n (%)

Caucasian 17 (58.6) 6 (17.6)< 0.01African-American 10 (34.5) 25 (73.5)

Hispanic 2 (6.9) 3 (8.8)Social history, n (%)

Tobacco 12 (41.4) 9 (26.5) 0.22Alcohol 7 (24.1) 10 (29.4) 0.64

Cocaine or heroin 2 (6.9) 7 (20.6) 0.12Marijuana 2 (6.9) 3 (8.8) 0.78

N = 63

Results: Baseline CharacteristicsCharacteristic Venlafaxine

(n = 29)

Citalopram

(n = 34)

p-value

Mean SBP prior to initiation (mm Hg), n (SD) 130 (17) 131 (19) 0.94

Mean DBP prior to initiation (mm Hg), n (SD) 74 (12) 72 (13) 0.64

W i ht t t (BMI) (%)Weight status (BMI), n (%)

Underweight, < 18.5 0 (0.0) 0 (0.0)

0.31

Normal, 18.5 - 24.9 6 (20.7) 11 (32.4)

Overweight, 25.0 - 29.9 7 (24.1) 12 (35.3)

Obesity I, 30.0 -34.9 8 (27.6) 5 (14.7)

Obesity II, 35.0 - 39.9 5 (17.2) 3 (8.8)

Obesity III, ≥ 40 3 (10.3) 3 (8.8)

N = 63




Atrial fibrillation, n (%) 6 (20.7) 7 (20.6) 0.55

H i (%) 29 (100 0) 33 (97 1) 0 3Hypertension, n (%) 29 (100.0) 33 (97.1) 0.35

Chronic kidney disease, n (%) 1 (3.4) 15 (44.1) < 0.01

Anemia, n (%) 2 (6.9) 6 (17.6) 0.20

Diabetes mellitus, n (%) 15 (51.7) 19 (55.9) 0.74

Hypothyroidism, n (%) 2 (6.9) 4 (11.8) 0.51

N = 63

8/10/2010

5




Baseline HF, n (%)

Diastolic 6 (20.7) 10 (29.4) 0.69

Systolic 6 (20 7) 15 (44 1) 0 26Systolic 6 (20.7) 15 (44.1) 0.26

No diagnosis of HF at baseline 17 (58.6) 9 (26.5) 0.10

Indication for use, n (%)

Depression 22 (75.9) 24 (70.6)

0.09Post traumatic stress disorder 5 (17.2) 2 (5.9)

Generalized anxiety disorder 1 (3.4) 4 (11.8)Narcolepsy 1 (3.4) 0 (0.0)

> 1 indication 0 (0.0) 4 (11.8)

N = 63


• Baseline EF not available for all subjects

• Of the subjects with baseline EF:

EF Venlafaxine(n = 17)

Citalopram (n = 26) p-value

≥ 40 16 (96.6) 16 (70.6)0.04

< 40 1 (3.4) 10 (29.4)

n = 43

Definitions

• New HF diagnosis• First occurrence of HF during the study period in

patients without pre-existing HF

• HF exacerbation• Any occurrence of HF during the study period in

patients with a prior diagnosis of HF

• HF event• Both new HF diagnoses and HF exacerbations

Results: Venlafaxine Arm

HF + Venlafaxine (n = 29)

HF diagnosis prior to SNRI initiation (n = 12)

HF diagnosis post SNRI initiation (n = 17)SNRI initiation (n 12)

1 HF exacerbation

initiation (n 17)

21 HF events

17 new HF diagnoses

4 HF exacerbations

Results: Citalopram ArmHF + Citalopram

(n = 34)

HF diagnosis prior to SSRI initiation (n = 25)

HF diagnosis post SSRI initiation (n = 9)

17 HF exacerbations 10 HF events

9 new HF diagnoses

1 HF exacerbation

Results: HF Events

1717

9

Venlafaxine (22 events)

Citalopram (27 events)

1

4

9

1

Exacerbations in Patients with Baseline HF

New HF Diagnoses HF Exacerbations in Newly Diagnosed Patients

n = 49

(p = 0.18) (p = 0.01) (p = 0.54)

8/10/2010

6

Results: Event Clinical DataVenlafaxine

(n = 22)Citalopram

(n = 27) p-value

Median dose at event, mg (IQR) 150 (75 – 225) 20 (20 – 27.5) N/A

Mean change in weight from 4.1 (12.2) 0.7 (7.3) 0 53baseline, n (SD) 4.1 (12.2) 0.7 (7.3) 0.53

* Baseline data not available for all events

Venlafaxine(n = 8)*

Citalopram(n = 19)* p-value

Mean change in EF from baseline, % (SD) ‐6.9 (16.2) 2.6 (15.2) 0.16

Results: HF Therapy

Agent, n (%) Venlafaxine (n = 22)

Citalopram (n = 27) p-value

ACE inhibitor/ARB 17 (77) 24 (89) 0.32

β adrenergic antagonists 16 (73) 22 (81) 0.46

Diuretic(s) 9 (41) 24 (89) < 0.01

Digoxin 2 (9) 6 (22) 0.22

Aldosterone antagonist 2 (9) 0 (0.0) 0.11

Hydralazine + nitrate 1 (5) 2 (7) 0.68

n = 49

Results: Confounding MedicationsDetrimental Agent, n

(%)Venlafaxine

(n = 22)Citalopram

(n = 27) p-value

Antipsychotics* 6 (27) 0 (0) < 0.01

NSAIDs/COX-2 inhibitors 3 (14) 0 (0) 0.14

TCAs 2 (9) 0 (0) 0.29

Gl cocorticoids 2 (9) 0 (0) 0 11Glucocorticoids 2 (9) 0 (0) 0.11

Cytotoxic agents 1 (5) 2 (7) 0.68

IMM/antibodies 1 (5) 1 (4) 0.88

Non-DHP CCBs 1 (5) 1 (4) 0.88

Thiazolidinediones 1 (5) 0 (0) 0.26

Antiarrhythmics 1 (5) 0 (0) 0.26

Androgens 1 (5) 0 (0) 0.26

n = 49* Antipsychotics, n = 6: risperidone, 5; olanzapine, 1

Results: Time to Event

SUBSEQUENT EVENTSV l f i Cit l

FIRST EVENTVenlafaxine

(n = 18)Citalopram

(n = 16) p-value

Median time to first event, months (IQR)

27.5 (20.3 – 39)

14.5 (4.8 – 43.3) 0.33

Venlafaxine(n = 3)

Citalopram(n = 4)

Total number of exacerbations 4 11

Number of patients 1 exacerbation

2 exacerbations ≥ 3 exacerbations

210

211

Mean time between exacerbations, months (SD) 44.3 (35.9) 3.5 (4.0)

Results: Severity of HF Events

• All HF events were treated in the inpatient setting

o Venlafaxine (n=22) . . . . . . . . . . . . . . . . . . 22 (100%)

o Citalopram (n=27) . . . . . . . . . . . . . . . . . . . 27 (100%)

n = 49

Results: HF Events

1717Venlafaxine (22 events)

Citalopram (27 events)

1

4

9

1

Exacerbations in Patients with Baseline HF

New HF Diagnoses HF Exacerbations in Newly Diagnosed Patients

n = 49

(p = 0.18) (p = 0.01) (p = 0.54)

8/10/2010

7

Results: New HF Diagnoses

Characteristic Venlafaxine (n = 17)

Citalopram(n = 9)

p-value

Median time to diagnosis, 24 (20 39) 28 (11 50) 0 50g ,months (range) 24 (20 – 39) 28 (11 – 50) 0.50

Median dose at diagnosis, mg (range) 150 (75 – 225) 20 (20 – 20) N/A

n = 26

Discussion• No significant difference in HF events

between groupso Median venlafaxine dose at exacerbation (150

mg) is at the approximation where NE reuptake inhibition beginsinhibition begins

o Duloxetine exhibits equal reuptake inhibition of serotonin (5-HT) and NE across the dosing spectrum

No duloxetine arm was established for this study

Discussion

• Baseline differences in SNRI vs. SSRI treatment arms

o Patients in citalopram arm were older, had more severe HF, and a higher incidence of African Americans and CKDAmericans and CKD

o More patients on diuretics in citalopram armo 1 patient in the citalopram arm had 8 exacerbations

• Significant difference in concomitant antipyschotic therapy in venlafaxine arm

o 5 patients on risperidone; may increase risk of HFo This finding may be a confounding variable

Discussion

• Lack of association between initiation of SNRI and time to HF exacerbation

o Large distribution in datao Most exacerbations occurred > 6 months post-o Most exacerbations occurred 6 months post

initiation

• All exacerbations in the SNRI and SSRI groups were similar in severity, requiring inpatient treatment

Discussion

• Based on the patients reviewed, a significant difference was found for new diagnoses in the venlafaxine arm vs. citalopram arm

o No difference in time to diagnosis between agentsg g

o Median dose of venlafaxine at threshold of NE reuptake

o Confounders were not fully assessed

• Premature to assign clinical significance o Warrants future prospective studies

Limitations

• Retrospective study

• Potential for Type II error due to small sample size

L di t ib ti t f l k f• Large distribution may account for lack of significance in data

• Possible treatment of exacerbations at outside medical centers

• No duloxetine arm

• Medication adherence was not assessed

8/10/2010

8

Conclusion• No difference in rate, onset, or severity of

HF exacerbations was found between patients receiving venlafaxine and citalopramp

• Trend toward increased risk for new HF diagnosis with venlafaxine

Future Directions

• Prospective evaluation of HF patients on SNRIs vs. SSRIs comparing:

o Incidence of HF exacerbation o New onset HFo New-onset HF

• These prospective studies should include duloxetine due to its different dosing spectrum than venlafaxine

Self Assessment Question 1

True or False

Guidelines exist for the treatment of d i i ti t ith h t f ildepression in patients with heart failure.

Self Assessment Question 2

Which of the following medications may potentiate heart failure?

) Na) Naproxenb) Acetaminophenc) Rosiglitazoned) All of the abovee) A & C

Acknowledgements

• Jesse Brown VA Medical Center Clinical Pharmacy Service

o Donna M. Givone, Pharm.D., BCPPo Judith A. Toth, Pharm.D., CGP, CDE, FASCPo Judith A. Toth, Pharm.D., CGP, CDE, FASCP

• University of Illinois at Chicago Center for Clinical and Translational Services

Heart Failure Exacerbation Caused by Serotonin-Norepinephrine

Reuptake Inhibitors in a Veteran Population

Kelly L. Perez, Pharm.D.PGY-1 Pharmacy Resident

Jesse Brown VA Medical CenterChicago, Illinois28 August 2010

8/10/2010

9

References• Hunt SA, Abraham WT, Chin MH, Feldman AM, Francis GS, Ganiats TG, et al. 2009

Focused update incorporated into the ACC/AHA 2005 guidelines for the diagnosis and management of heart failure in adults: A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation 2009;119:e391–e479.

• Lloyd-Jones D, Adams R, Carnethon M, DeSimone G, Ferguson TB, Flegal K, et al. Heart disease and stroke statistics 2009 update: A report from the American Heart Association statistics committee and stroke statistics subcommittee. Circulation 2009 119 21 1812009;119:e21-e181.

• Slordal L, Spigset O. Heart failure induced by non-cardiac drugs. Drug Safety2006;29:567-586.

• Jiang W, Alexander J, Christopher E, Kuchibhatla M, Gaulden LH, Cuffe MS, et al. Relationship of depression to increased risk of mortality and rehospitalization in patients with congestive heart failure. Arch Intern Med 2001;161:1849-56.

• Thomas SA, Friedmann E, Khatta M, Cook LK, Lann AL Depression in patients with heart failure: physiologic effects, incidence, and relation to mortality. AACN Clin Issues 2003;14:3-12.

• Lane DA, Chong AY, Lip GY. Psychological interventions for depression in heart failure. Cochrane Database Syst Rev 2005;1: CD003329.

References, continued• Alvarez W, Pickworth K. Safety of antidepressant drugs in the patient with cardiac

disease: A review of the literature. Pharmacotherapy 2003;23:754-71. • Colucci VJ, Berry BD. Heart failure worsening and exacerbation after venlafaxine and

duloxetine therapy. Ann Pharmacother 2008;42:882-7.• Fangio P, DeJonghe B, Appere-De-Vecchi C, Lacherade JC, Terville JP, Outin H.

Acute heart failure associated with venlafaxine poisoning. Am J Emerg Med2007;25:210-11.

• Drent M Singh S Gorgels APM Hansell DM Bekers O Nicholson AG et al Drug-Drent M, Singh S, Gorgels APM, Hansell DM, Bekers O, Nicholson AG, et al. Druginduced pneumonitis and heart failure simultaneously associated with venlafaxine. Am j Respir Crit Care Med 2003;167:958-61.

• Hasking GJ, Elser MD, Jennings GL, Burton D, Korner PI. Norepinephrine spillover to plasma in patients with congestive heart failure:Evidence of increased overall and cardiorenal sympathetic nervous activity. Circulation 1986;73:615-21.

• Bleske BE. Evolution and pathophysiology of chronic systolic heart failure. Pharmacotherapy 2000;20:349S-58S.

• Baldessarini, RJ. Drug therapy of depression and anxiety disorders. In: Brunton LL, Lazo JS, Parker KL, editors. Goodman & Gilman’s The Pharmacological Basis of Therapeutics. 11th ed. New York: McGraw-Hill, Inc; 2006.

ICHP Annual Meeting 2010 Perez – Residency Project Pearls 121-000-10-056-L01-P �Post Test Question 1. True or False: Guidelines exist for the treatment of depression in patients with heart failure. 2. Which of the following medications may potentiate heart failure?

a) Naproxen b) Acetaminophen c) Rosiglitazone d) All of the above e) A and C

8/10/2010

1

PSYCHIATRIC ADVERSE EVENTS AND USE OF PSYCHOTROPIC

MEDICATIONS BEFORE & DURING INTERFERON TREATMENT FOR

HEPATITIS C (HCV)

Sheri VanOsdol Pharm.D.PGY-2 in Drug Information

University of Illinois, Chicago, Drug Information GroupAugust 28, 2010

The speaker has no conflict to disclose.

Objectives• List potential complications of untreated

Hepatitis C virus (HCV)

• Describe the complications of psychiatric p p yadverse effects that occur during HCV therapy

• Identify patients at higher risk for developing psychiatric adverse effects during HCV therapy

Natural History of HCV

Acute Infection

Chronic Infection

85%

Recover15%

Chronic Hepatitis

Mild, Moderate, Severe

70%

20% Cirrhosis

1- 4 %/ yr

Death

HCC

0 10 20 30Time (Years)CDC Division of Viral Hepatitis, 2009

HCV Treatment• Goal: Achieve Sustained Virologic Response (SVR)

– Undetectable viral load 24 weeks after treatment discontinuation

• Factors associated with a decreased likelihood of sustaining SVRsustaining SVR– Genotype 1– High baseline viral load– African American ethnicity– Liver transplant recipient– Previous treatment failures– Uncontrolled diabetes

Muir et. al, 2004Ghany et.al., 2009

HCV Treatment• Pegylated Interferon (PegIFN) & Ribavirin

– PegIFN alfa-2a or 2b administered SC weekly– Ribavirin twice daily dose depends on PegIFN & HCV

genotype

Ghany et.al., 2009

Genotype Duration of Therapy

1, 4 48 weeks recommended (up to 72 weeks)

2, 3 24 weeks recommended (up to 48 weeks)

5, 6 No specific guidelines for the U.S.

PegIFN• Flu-like symptoms • Injection site reactions• Neutropenia• Thrombocytopenia

Th id d f ti

• Hemolytic anemia• Dyspnea• Chest pains• Pruritus

R h

Adverse Effects of TreatmentRibavirin

• Thyroid dysfunction • Insomnia• Rash and pruritus• Anorexia• Diabetes• Hyperlipidemia• Psychiatric disorders

• Depression, irritability

• Rash • Cough • Anorexia • Teratogenicity

8/10/2010

2

• In psychiatric patients, HCV prevalence is 6.8 - 8.5% • Registration trials of PegIFN alfa-2a & 2b + Ribavirin

– 10-14% dropout due to AEs• >50% flu-like symptoms• 22-31% psychiatric AEs

Depression & HCV Treatment

• 22-31% psychiatric AEs• Interferon-specific depression

– Mood, anxiety, cognitive complaints– Fatigue, anorexia, pain, psychomotor slowing

• Psychiatric AEs correlate to poor treatment adherence– Impact on SVR is unclear

Self Assessment Question

Which of the following factors make a patient a better candidate for achieving sustained virological response to HCV therapy?

a. Genotype 1 diseaseb. African American ethnicityc. Uncontrolled diabetesd. HCV RNA level less than 300,000 IU/mL

Self Assessment Question

True or False:

The incidence of psychiatric adverse effects associated with interferon or pegylatedassociated with interferon or pegylated interferon therapy ranges between 5% to 20%.

Study Objectives

• Aim 1: To assess the incidence of new onset psychiatric adverse events and new or increased psychotropic medication use after the initiation of interferon therapyafter the initiation of interferon therapy

• Aim 2: To identify risk factors associated with psychotropic medication use and/or psychiatric adverse events in subjects receiving treatment for HCV

METHODS

Study Design

• Retrospective chart review• Reviewed all subjects evaluated for HCV

therapy at UIMC outpatient liver clinic from July 1999 through August 2009g g

• Utilized objective reporting of psychotropic medication use as surrogate marker for depressive or other psychiatric symptoms

• This study was IRB approved by our institution on 10/22/2009 prior to data collection

8/10/2010

3

Subject Selection

• Inclusion criteria– All patients ≥ 18 years old– Receiving PegIFN + Ribavirin– First round of HCV therapy at UIMC

• Exclusion criteria– HIV– Hepatitis B– HCV therapy from outside provider– Therapy taking place outside the pre-specified date

range

Data CollectionBaseline• Sex• Age• Race

All Visits• Viral Load• Psychotropic

MedicationsH l bi• Height & Weight

• HCV Genotype• Past Medical History• Risk Factors for HCV

• Hemoglobin• Weight

Statistical Analysis

• Student’s T-test was used to correlate new or worsened psychiatric effects with– Age– BMI

• Chi-squared test was used to correlate new or worsened psychiatric effects with– Sex– Race– Baseline psychotropic medication use– Treatment response

Definitions• Psychotropic medications: antidepressants,

antipsychotics, mood stabilizers, anxiolytics, sedative hypnotics

• Psychotropic medication history: use of psychotropic di ti i t i iti ti f HCV thmedications prior to initiation of HCV therapy

• New/worsened psychiatric adverse events during therapy: addition of new medication, increased dose of current medication, or change of drug as surrogate maker for new/worsened psychiatric symptoms at any time during HCV treatment

Definitions• Treatment response: achievement of undetectable

viral load before discontinuation of therapy

• Non-response: undesirable change in viral load leading to discontinuation of therapy; change from treatment to maintenance dosing for PegIFNtreatment to maintenance dosing for PegIFN

• Lost to follow-up: patients who self-discontinued therapy for financial reasons or unknown reasons

• Side effects: therapy discontinued by patient or provider due to side effects (e.g. uncontrolled anemia, psychiatric hospitalization, hallucinations, anhedonia, severe anorexia, etc.)

RESULTS

8/10/2010

4

409 charts screened

Excluded patients (238):169 never treated

15 HIV + 6 HBV +

2 on maintenance therapy32 treated by outside provider

54 patients experienced psychiatric AEs on HCV

therapy31.6%

117 patients had no psychiatric AEs while on

HCV therapy68.4%

32 treated by outside provider14 treated outside of study

period171 patients included

Baseline DemographicsCharacteristic Mean Male 61%Mean Age 49 yrMean BMI 29Initial Drug 33.9%Genotype (n=168)

1 67.3% (113)2 19 6% (33)2 19.6% (33)3 11.9% (20)4 1.2% (2)

Stage (n=117)1 11.1% (11)2 38% (45)3 24% (28)4 26% (31)

Treatment naïve (n=162) 63.4% (161)

Baseline Characteristics: RaceAsian 1.8%

Other 5.3%

Caucasian 34%

African American 38%

Hispanic 21%

n=171

Distribution by RaceTotal

(n=171)New/

Worsened Psychiatric AEs (n=54)

No Psychiatric

AEs(n=117)

p-value

Psychiatric AEs (%) 31.6 68.4AEs (%)

African American (%) 38 29.6 41.2

0.23Non-Hispanic

White (%) 34 44.4 29.1

Hispanic (%) 21 20.4 21.4

Other (%) 7 5.6 7.7

Baseline CharacteristicsTotal

(n=171)New/

Worsened Psychiatric AEs (n=54)

No Psychiatric

AEs(n=117)

p-value

Psychiatric AEs (%) 31.6 68.4 --

Male (%) 61 64 8 59 NS

Depression (%) 23 27.8 20.5 --

Bipolar (%) 2.3 3.7 1.7 --Anxiety (%) 2.3 5.6 0.9 --

Schizophrenia (%) 1.8 5.6 0 --

Male (%) 61 64.8 59 NSMean Age (yr) 49 48.9 +/- 8.8 48.7 +/- 9.6 NS

Mean BMI 29 29 +/- 6.4 29.2 +/- 7 NSInitial Drug (%) 33.9 46.3 28.2 0.02

Discontinuation of Therapy

30354045

Total Population(n=171)

atio

n tio

n 29.2

40.9

05

10152025

Responder Non-responder Lost-to follow-up

Adverse Effects

% D

isco

ntin

uaTo

tal P

opul

a

16.413.5

8/10/2010

5

Discontinuation of Therapy

40

50

60 Psychiatric AEs(n=54)

No Psychiatric AEs(n=117)

nuat

ion

oup

51.9

29 935.9

9.3 11.1

0

10

20

30

Responder Non-responder Lost-to follow-up

Adverse Effects

p=0.19

% D

isco

ntin

by G

ro

18.8

29.9

15.4

27.8

11.19.3

Conclusion

• Subjects using psychotropic medications prior to initiation of HCV therapy were statistically more likely to develop depression or other psychiatric symptoms while on HCV therapy

• No correlations were made between response to therapy or treatment discontinuation

• No correlation was made with new/ worsened psychiatric AEs– Sex, age, race, BMI, reason for discontinuation of

HCV therapy

Discussion

Study Limitations• Inconsistency of documentation • Medication use as surrogate marker• Depression vs other psychiatric AEs• Referral center• Inability to obtain SVR• Exclusion of HIV+, Hepatitis B+ patients

Future Analysis: Genotype, previous treatment, trends in hemoglobin, duration of treatment

Impact on Clinical Practice

• Proposed use of validated depression screening tools at baseline and follow-up visits for patients undergoing HCV therapy– Beck Depression Inventoryp y– Zung Self-Rating Depression Scale

ReferencesCDC Division of Viral Hepatitis - Statistics and Surveillance 2009. Dinwiddie SH, Shicker L, Newman T. Prevalence of hepatitis C among psychiatric patients in the public sector. Am J Psychiatry 2003;160:172-4. Fireman M, Indest DW, Blackwell A, Whitehead AJ, Hauser P. Addressing tri-morbidity (hepatitis C, psychiatric disorders, and substance use): the importance of routine mental health screening as a component of a comanagement model of care. Clin Infect Dis 2005;40 Suppl 5:S286-91. Ghany MG, Strader DB, Thomas DL, Seeff LB, American Association for the Study of Liver Diseases Diagnosis management and treatment of hepatitis C: an updateLiver Diseases. Diagnosis, management, and treatment of hepatitis C: an update. Hepatology 2009;49:1335-74. Hadziyannis SJ, Sette H,Jr, Morgan TR, et al. Peginterferon-alpha2a and ribavirin combination therapy in chronic hepatitis C: a randomized study of treatment duration and ribavirin dose. Ann Intern Med 2004;140:346-55. Janke EA, McGraw S, Garcia-Tsao G, Fraenkel L. Psychosocial issues in hepatitis C: a qualitative analysis. Psychosomatics 2008;49:494-501. Kristofco RE, Stewart AJ, Vega W. Perspectives on disparities in depression care. J

Contin Educ Health Prof 2007;27 Suppl 1:S18-25.

ReferencesMartin-Santos R, Diez-Quevedo C, Castellvi P, et al. De novo depression and anxiety disorders and influence on adherence during peginterferon-alpha-2a and ribavirin treatment in patients with hepatitis C. Aliment Pharmacol Ther 2008;27:257-65. Menkes DB, MacDonald JA. Interferons, serotonin and neurotoxicity. Psychol Med 2000;30:259-68. Muir AJ, Bornstein JD, Killenberg PG, Atlantic Coast Hepatitis Treatment Group. Peginterferon alfa-2b and ribavirin for the treatment of chronic hepatitis C in blacks and non-Hispanic whites. N Engl J Med 2004;350:2265-71. National Institutes of Health Consensus Development Conference Statement: M t f h titi C 2002 (J 10 12 2002) G t t lManagement of hepatitis C 2002 (June 10-12, 2002). Gastroenterology 2002;123:2082-99. Nguyen HA, Miller AI, Dieperink E, et al. Spectrum of disease in U.S. veteran patients with hepatitis C. Am J Gastroenterol 2002;97:1813-20. Raison CL, Borisov AS, Broadwell SD, et al. Depression during pegylated interferon-alpha plus ribavirin therapy: prevalence and prediction. J Clin Psychiatry 2005;66:41-8. Rosenberg SD, Goodman LA, Osher FC, et al. Prevalence of HIV, hepatitis B, and hepatitis C in people with severe mental illness. Am J Public Health 2001;91:31-7. Schaefer M, Schmidt F, Folwaczny C, et al. Adherence and mental side effects during hepatitis C treatment with interferon alfa and ribavirin in psychiatric risk groups. Hepatology 2003;37:443-51.

Evaluation of Edward Hines, Jr. VA Hospital

Documents

Transcript of Evaluation of Edward Hines, Jr. VA Hospital