Pharmacologic Debridement: More Does Not Equal Better Jacob B. Blumenthal, MD, FACP Baltimore Geriatrics Research, Education and Clinical Center/VAMC University.

Pharmacologic Debridement: More Does Not Equal Better

Jacob B. Blumenthal, MD, FACP Baltimore Geriatrics Research, Education and Clinical Center/VAMC

University of Maryland School of MedicineBaltimore, MD

[email protected]

Nicole J. Brandt, PharmD, CGP, BCPP, FASCPPeter Lamy Center on Drug Therapy and Aging

University of Maryland, School of PharmacyBaltimore, MD

[email protected]

…but…

• Unlike Dick the Butcher– ”The first thing we do, let's kill all the lawyers”

• Not: medications are bad– Rather, suggesting need for judicious use and

continuous re-litigation

Henry VI William Shakespeare

Outline

• Demographics – Aging and Multimorbidities– Polypharmacy and ADR’s

• Age-related changes– Pharmacodynamics (absorption, clearance)– Body Composition

• What are we doing? Whose standard?• Bad Drugs: Beer’s List, HEDIS High Risk Meds• Semper Vigilentes – Med Review as a SOP

The Demographic Imperative

• Population Explosion– Where we are:

• Over 65 years old: 12.9% of population• Over 75: 6.1% 18,766,000

– Where we’re going

US Census Bureau

Prevalence of Multimorbidities

Arch Intern Med. 2002;162(20):2269-2276. doi:10.1001/archinte.162.20.2269

Carey EC et al. JAGS 2008; 56:68–75.

Risk for Mortality in Frail Elders

Risks:Male = 2 pointsCHF = 3 pointsAge >85 = 3 points

…which influence prognosis

Nonetheless, Demographically…

• Compression of Morbidity

Fries, 1982

The Search for Clinical Decision Making Tools

• Large heterogeneity difficult to find applicable studies– “No index…prospectively tested and found to be accurate in a

large diverse sample…no study was completely free from potential sources of bias. Testing of transportability was limited, raising concerns about overfitting and underfitting. These factors limit a clinician's ability to assess the accuracy of these indices across patient groups that differ according to severity of illness, methodology of data collection, geographic location, and time.”

• The Controversy– How far can we extrapolate data for this population? – To what extent can we base clinical practice on biologic

plausibility in the absence of clinical trail data?

Importance of Multimorbidity• Over 50% of older adults have 3+ chronic conditions

• Increased risk of: – Death– Institutionalization– Increased utilization of healthcare resources – Decreased quality of life– Higher rates of adverse effects of treatment or

interventions

• Almost all existing “guidelines” have single disease focus

• Best approaches to decision-making and clinical management of older adults with multimorbidity remain unclear

Brendan Smialowski (NY Times)

Prevalence of Polypharmacy…

Qato et al JAMA 2008: 300(24): 2867-2878

Treatment Complexity & Feasibility

• Difficult to define a uniform threshold for treatment complexity and feasibility

• Influenced by – Treatment regimen– Older adult’s unique characteristics

• Barriers to assessing complexity and feasibility– Time-consuming– Lack of necessary training

Drugs are not benign• ~100,000 emergency hospitalizations/year due

to adverse drug events (ADEs)

• 10.7% of hospital admissions in older adults

• “If medication related problems were ranked as a disease, it would be the fifth leading cause of death in the US!”

Kongkaew C, et al. Annals of Pharmacotherapy 2008; 42:1017-1025Budnitz et al. N Engl J Med 2011;365:2000-12.Beers MH. Arch Internal Med. 2003

Pharmacokinetics Change with Age

• Absorption– Other drugs, nutrition, gastric emptying

• Distribution– ↑adipose/↓lean, water

• Binding/Localization– ↓albumin

• Biotransformation– ↓Hepatic Clearance (some drugs), great variability

• Elimination– ↓GFR

…and diminished homeostatic reserve

Need for Balance

Risk…

Rane A, Lindh JD. Hum Genomics Proteomics 2010

…mitigated by other meds….

Rane A, Lindh JD. Hum Genomics Proteomics 2010

Need for Balance

Benefit…

Rane A, Lindh JD. Hum Genomics Proteomics 2010

Need for Balance

Benefit…all of it!

Rane A, Lindh JD. Hum Genomics Proteomics 2010

Need for Balance

TIME

% e

vent

-fre

e

Is the effect statistically and/or clinically significant?

Is there a wide variation in time to benefit, or by subgroups?

Diabetes Mellitus

ADA Standards of Medical Care in Diabetes 2012. Sjoblom P. Diabetes Res Clin Prac 2008; 82:197-202.

• Less stringent control reasonable in those with a long history of diabetes, limited life expectancy, or comorbid conditions

Drug withdrawal study in 17 nursing homes in patients with HbA1c <6: safe to discontinue all oral meds, and stop or reduce insulin

Top Five Problematic Medication Classes leading to ED

1. Hematologic 2. Endocrine agents3. Cardiovascular agents4. Central Nervous System

Agents5. Anti-infective

Budnitz et al. N Engl J Med 2011;365:2000-12.2

Oral Antiplatelet

Warfarin

67%

Oral Hypoglycemic

Insulin

…including time to benefit

PROSPER. Lancet 2002; 360: 1623–30.

Proportion in the PROSPER Trial with CHD Death, Non-Fatal MI, or Stroke

Osteoporosis

TIME

% fr

actu

re-f

ree

Prevention of osteoporotic fracture

50% reduction in risk of fracture over a 3 year period

1.2% absolute risk reduction for fractures in 3 years

Benefits possibly similar in men, but data is extrapolated from studies of women

Median life expectancy: 2.7- 4.7 years

Time to benefit 9 to 18 mos

bisphosphonate

National Osteoporosis Foundation. Clinician’s guide to prevention and treatment of osteoporosis, 2009

placebo

No “best” approach to either communicate prognosis nor effect “optimal” clinical decision making

Guidelines lack adequate ways to assess prognosis

Published prognosis measures have limited generalizability

Overwhelming to evaluate prognosis Uncertainty in how to use prognostic

measures in clinical practice

Consider patient preferences…

• Influenced by the way risk information is presented to the patient

• Multimorbidity patients face more preference-based and complex decisions

• Eliciting preferences may make clinical management more time-consuming

Medication Management Capacity Drug Regimen Unassisted Grading Scale (DRUGS)

Edelberg HK, Shallenberger E, Wei JY. Medication management capacity in highly functioning community-living older adults: detection of early deficits. J Am Geriatr Soc. 1999 May;47(5):592-6.

Hopkins Medication Schedule (HMS) Carlson MC, Fried, LP, Xue QL, et al. Validation of the Hopkins Medication

Schedule to Identify Difficulties in Taking Medications Journal of Gerontology: Feb 2005;60A,2: Health Module 217-223

Medication Management Instrument for Deficiencies in the Elderly (MedMaIDE)

Orwig D, Brandt N, Gruber-Baldini, A. Medication Management Orwig D, Brandt N, Gruber-Baldini, A. Medication Management Assessment for Older Adults in the Community. The Gerontologist Assessment for Older Adults in the Community. The Gerontologist 2006;46:661-6682006;46:661-668

…and patient capabilities

PUTTING IT ALL TOGETHER…

Inappropriate Prescribing

Methods to Look at Inappropriate Prescribing e.g.:– American Geriatrics Society 2012 Beer’s Criteria– STOPP (Screening Tool of Older Persons’

potentially inappropriate Prescriptions)– START (Screening Tool to Alert doctors to the

Right Treatment)– Clinical Judgment

Hamilton HJ. Inappropriate Prescribing and adverse drug events in older people. BMJ Geriatrics (2009). Accessed at www.biomedcentral.com/1471-2318/9/5

Bergert FW, Conrad D, Ehrenthal EJ et al. Pharmacotherapy Guidelines for the aged by family doctors for the use of family doctors. Inter J Clin Pharm Ther (2008) 46:600-616.

HISTORY AND DEVELOPMENT OF HISTORY AND DEVELOPMENT OF THE AGS 2012 BEERS CRITERIATHE AGS 2012 BEERS CRITERIA

Mark H Beers, MD1954-2009

“ A ballet-dancing opera critic who hiked the Alps and took up rowing after diabetes cost him his legs”

•MD, University of Vermont•First medical student to do a geriatrics elective at Harvard‘s new Division on Aging•Geriatric Fellowship, Harvard•Faculty, UCLA/RAND•Co-editor, Merck Manual of Geriatrics•Editor in Chief, Merck Manuals

Beers Criteria: History and Utilization • Original 1991 – Nursing home pts• Updates

– 1997: All elderly; adopted by CMS in 1999 for nursing home regulation

– 2003: Era of generalization to Med D, then NCQA, HEDIS

– 2012: Further adoption into quality measures

Specific Aims AGS 2012 Beers Criteria

Specific aim – update 2003 Beers Criteria using a comprehensive, systematic review and grading of evidence

Strategy:1. Incorporate new evidence2. Grade the evidence3. Use an interdisciplinary panel4. Incorporate exceptions

Method

Framework• Expert panel

– 11 members

• IOM 2011 report on guideline development– Includes a period for public comment

• Literature search

Panel Members

• Co-chairs– Donna Fick, PhD– Todd Semla, MS, PharmD

• Panelists (voting)– Judith Beizer, PharmD– Nicole Brandt, PharmD– Catherine DuBeau, MD– Nina Flanagan, CRNP,CS-BC– Joseph Hanlon, PharmD, MS– Peter Hollmann, MD– Sunny Linnebur, PharmD– Stinderpal Sandhu, MD– Michael Steinman, MD

• Nonvoting Panelists– Robert Dombrowski, PharmD

(CMS)– David Nau, PhD (PQA)– Bob Rehm (NCQA)

• AGS Staff– Christine Campenelli– Elvy Ickowicz, MPH

• Others– Sue Radcliff (research)– Susan Aiello, DVM (editing)

Method• Literature search: ADE, inappropriate drug use, med

errors, polypharmacy x age/human/English

25,549 citations 12/1/2001 – 3/30/2011

6,505 prelim review

844 excluded

2169 reviewed

258 included in evidence tables

Additional searches, additions

Additional searches, additions

19,044 excluded

2,267 reviewed by co-chairs

4238 excluded

Method• Survey to panel to rate (strong agreestrong

disagree)– 2003 Beers meds– New additions

• Ratings tallied, shared with panel, 2 rounds of consensus

• In-person: review survey draft and lit search• 4 groups reviewed lit, selected citations• Evidence tables prepared, rated quality of evidence

and strength of recommendation• Final group consensus

Designations of Quality and Strength of Evidence: ACP Guideline Grading System, GRADE

Quality• High Evidence

– Consistent results from well-designed, well-conducted studies that directly assess effects on health outcomes (2 consistent, higher-quality RCTs or multiple, consistent observational studies with no significant methodological flaws showing large effects)

• Moderate Evidence – Sufficient to determine effects on health outcomes, but the number, quality, size, or

consistency of included studies, generalizability, indirect nature of the evidence on health outcomes (1 higher-quality trial with > 100 participants; 2 higher-quality trials with some inconsistency, or 2 consistent, lower-quality trials; or multiple, consistent observational studies with no significant methodological flaws showing at least moderate effects) limits the strength of the evidence

• Low Evidence– Insufficient to assess effects on health outcomes because of limited number or power of

studies, large and unexplained inconsistency between higher-quality studies; important flaws in design or conduct, gaps in the chain of evidence

– Or lack of information on important health outcomes

Designations of Quality and Strength of Evidence: ACP Guideline Grading System, GRADE

Strength of recommendation• Strong:

– Benefits clearly > risks and burden OR risks and burden clearly > benefits

• Weak: – Benefits finely balanced with risks and burden

• Insufficient: – Insufficient evidence to determine net benefits or risks

AGS 2012 BEERS CRITERIACLINICAL HIGHLIGHTS & EVIDENCE

Need for Updates or New Criteria

•Continuous arrivals of new drugs on the market1

•Older formulations unavailable in European formularies2

•Only 12-21% of the medications identified are being used by older adults3

•Tangible benefit to patients in terms of clinical outcomes2

Fick D, Cooper J, Wade W, et al. Arch Intern Med 2003;163:2716-2724 1

Hamilton H, Gallagher P, Ryan C, Arch Intern Med 2011;171(11):1013-1019 2 Rudolph J, Salow M, Angelini M et al. Arch Inern Med 2008; 168 (5): 508-513 3

Beers Criteria- 3 Main Tables 1) Table 2: Medications or medication classes that

should be avoided in persons 65 years or older

1) Table 3: Medications that should not be used in older person known to have specific medical diseases or conditions.

1) Table 4: Medications that should be used with caution

Beers Criteria: Overall Results

• A total of 53 medications or medication classes, which are divided into three tables.

• Constructed and organized by:– major therapeutic classes and – organ systems

Beers Criteria: Table 2 Results

– 34 potentially inappropriate medications/classes to avoid in older adults independent of diagnoses or conditions.

– Notable mentions: –Sliding Scale Insulin–Antipsychotics for Behavioral Health

issues associated with dementia–Non benzodiazepine Hypnotics–Megestrol

Sliding Scale Organ System/ Therapeutic Category/Drug(s)

Rationale Recommendation

Quality of Evidence

Strength of Recommendation

References

Insulin, sliding scale

Higher risk of hypoglycemia without improvement in hyperglycemia management regardless of care setting.

Avoid Moderate Strong Queale 1997

Important to look at during transitions in care due to the fact that PO Diabetes meds are stopped when they are admitted and

typically have insulin protocols in place.

Antipsychotics Organ System/ Therapeutic Category/Drug(s)

Rationale Recommendation

Quality of Evidence

Strength of Recommendation

References

Antipsychotics, first- (conventional) and second- (atypical) generation (see Table 8 for full list)

Increased risk of cerebrovascular accident (stroke) and mortality in persons with dementia.

Avoid use for behavioral problems of dementia unless non-pharmacologic options have failed and patient is threat to self or others.

Moderate

Strong Dore 2009 Maher 2011 Schneider 2005 Schneider 2006a Schneider 2006b Vigen 2011 Timely addition with the increased focus on safety and

efficacy in patients on these medications especially within the nursing home setting.

Non Benzodiazepine Hypnotics Organ System/ Therapeutic Category/Drug(s)

Rationale Recommendation

Quality of Evidence

Strength of Recommendation

References

Nonbenzodiazepine hypnotics Eszopiclone Zolpidem Zaleplon

Benzodiazepine-receptor agonists that have adverse events similar to those of benzodiazepines in older adults (e.g., delirium, falls, fractures); minimal improvement in sleep latency and duration.

Avoid chronic use (>90 days)

Moderate Strong Allain 2005 Cotroneo 2007 Finkle 2011 McCrae 2007 Orriols 2011 Rhalimi 2009

Megestrol

Organ System/ Therapeutic Category/Drug(s)

Rationale Recommendation

Quality of Evidence

Strength of Recommendation

References

Megestrol Minimal effect on weight; increases risk of thrombotic events and possibly death in older adults.

Avoid Moderate

Strong Bodenner 2007 Reuben 2005 Simmons 2005 Yeh 2000

Beers Criteria: Table 3 Notables

Disease/Syndrome Drug/Drug Class RationaleHeart failure NSAIDs and COX-2

inhibitorsNondihydropyridine CCBs (avoid only for systolic heart failure)DiltiazemVerapamilPioglitazone, rosiglitazoneCilostazolDronedarone

Potential to promote fluid retention and/or exacerbate heart failure

Syncope Acetylcholinesterase inhibitors (CEIs)Peripheral alpha blockersTertiary TCAsChlorpromazine, thioridazine, and olanzapine

Increases risk of orthostatic hypotension or bradycardia

Beers Criteria: Table 3 Notables

Disease/Syndrome

Drug/Drug Class Rationale

History of falls or fractures

AnticonvulsantsAntipsychoticsBenzodiazepinesNonbenzodiazepine hypnoticsEszopicloneZaleplonZolpidemTCAs and SSRIs

Ability to produce ataxia, impaired psychomotor function, syncope, and additional falls; shorter-acting benzodiazepines are not safer than long-acting ones

Delirium All TCAsAnticholinergicsBenzodiazepinesChlorpromazineCorticosteroidsH2r receptor antagonists.

MeperidineSedative hypnoticsThioridazine

Avoid in older adults with or at high risk of delirium because of inducing or worsening delirium in older adults; if discontinuing drugs used chronically, taper to avoid withdrawal symptoms.

Beers Criteria: Table 4 Notable MentionsDrug Rationale Recommendation

ASA for Primary Prevention of cardiac events

Limited data in individuals > 80 Use with caution in adults > 80

Antipsychotics Carbamazepine Carboplatin Chlorpropamide Cisplatin Mirtazapine SNRIs SSRIs TCAs Vincristine

May exacerbate or cause SIADH or hyponatremia; need to monitor sodium level closely when starting or changing dosages in older adults due to increased risk

Use with caution

Limitations• Older adults often under-represented in drug

trials potentially underestimating medication related problems/evidence grading.

• Does not comprehensively address the needs of palliative and hospice care patients

• Does not address other types of potential potentially inappropriate medications– e.g.:

• dosing of primarily renally eliminated medications,• drug-drug- interactions

Take Home Points

• This is just one tool that can be utilized to optimize medication management in older adults.

• Need to make sure the Beers list is used in a patient centered manner

Resources Available Onlinewww.americangeriatrics.org

For the Health Professional• Downloadable pocket card• Evidence tables with links to supporting

references• Beers app – AGS iGeriatricsFor the Layperson• Summary in lay language• Q & A on what to do if one of your drugs is on the

Beers list• Medication diary & tips for safe use of meds

Evidence Tables

Patient Education

Beers Criteria only Part of Quality Prescribing Quality prescribing includes:• Correct drug for correct diagnosis • Appropriate dose (label; dose adjustments

for co-morbidity, drug-drug interactions) • Avoiding underuse of potentially important

medications (e.g., bisphosphonates for osteoporosis)

• Avoiding overuse (e.g., antibiotics) • Avoiding potentially inappropriate drugs • Avoiding withdrawal effects with

discontinuation • Consideration of cost

Follow-up Prescribing Decision

-Maintain drug-Change dose, frequency,

form-Discontinue-Substitute

-Add new drug

Monitor-Side effects, effectiveness

and adherence-Assess if med still needed

The Enhanced Monitoring Framework

Modified from: Steinman MA et al. Beyond the prescription: Medication monitoring and adverse drug events in older adults. JAGS. 2011;59(1):1513-20.

Primary ConcernPrimary Concern

Patient preference and feasibilityPatient preference and feasibility

Initial prescribing

decision

Initial prescribing

decision

Patient Education and Activation

Educate and activate patient to understand and report med-

related problems

Complete ReviewIncluding meds

Complete ReviewIncluding meds

Evidence and guidelinesPrognosis

Evidence and guidelinesPrognosis

?Interactions?Interactions

?benefits/harms?benefits/harms

Why is this important?

• Quality Metrics – HEDIS:

http://www.ncqa.org/HEDISQualityMeasurement/HEDISMeasures/HEDIS2013/HEDIS2013FinalNDCLists.aspx

• Improved patient care• Decrease liability

Take Home Points

• Medication Management & Monitoring takes a team!

• It needs to be patient centered.

• Most importantly, monitoring needs to be evaluated on an ongoing basis.