Pharmacologic Debridement: More Does Not Equal Better

1
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 Medicine
• Baltimore, MD
• jblument_at_grecc.umaryland.edu
• Nicole J. Brandt, PharmD, CGP, BCPP, FASCP
• Peter Lamy Center on Drug Therapy and Aging
• University of Maryland, School of Pharmacy
• Baltimore, MD
• nbrandt_at_rx.umaryland.edu

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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
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Outline

• Demographics
• Aging and Multimorbidities
• Polypharmacy and ADRs
• Age-related changes
• Pharmacodynamics (absorption, clearance)
• Body Composition
• What are we doing? Whose standard?
• Bad Drugs Beers List, HEDIS High Risk Meds
• Semper Vigilentes Med Review as a SOP

4
The Demographic Imperative

• Population Explosion
• Where we are
• Over 65 years old 12.9 of population
• Over 75 6.1 18,766,000
• Where were going

US Census Bureau
5
Prevalence of Multimorbidities
Arch Intern Med. 2002162(20)2269-2276.
doi10.1001/archinte.162.20.2269
6
which influence prognosis
Risk for Mortality in Frail Elders
Risks Male 2 points CHF 3 points Age gt85 3
points
Carey EC et al. JAGS 2008 566875.
7
Nonetheless, Demographically

• Compression of Morbidity

Fries, 1982
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The Search for Clinical Decision Making Tools

• Large heterogeneity ? difficult to find
  applicable studies
• No indexprospectively tested and found to be
  accurate in a large diverse sampleno 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?

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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)
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Prevalence of Polypharmacy
Qato et al JAMA 2008 300(24) 2867-2878
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Treatment Complexity Feasibility

• Difficult to define a uniform threshold for
  treatment complexity and feasibility
• Influenced by
• Treatment regimen
• Older adults unique characteristics
• Barriers to assessing complexity and feasibility
• Time-consuming
• Lack of necessary training

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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 421017-1025 Budnitz et al. N Engl J Med
20113652000-12. Beers MH. Arch Internal Med.
2003
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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
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Need for Balance
Risk
Rane A, Lindh JD. Hum Genomics Proteomics 2010
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mitigated by other meds.
Rane A, Lindh JD. Hum Genomics Proteomics 2010
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Need for Balance
Benefit
Rane A, Lindh JD. Hum Genomics Proteomics 2010
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Need for Balance
Benefitall of it!
Rane A, Lindh JD. Hum Genomics Proteomics 2010
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Need for Balance
Is the effect statistically and/or clinically
significant?
event-free
Is there a wide variation in time to benefit, or
by subgroups?
TIME
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Diabetes Mellitus

• 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 lt6 safe to discontinue all
  oral meds, and stop or reduce insulin

ADA Standards of Medical Care in Diabetes 2012.
Sjoblom P. Diabetes Res Clin Prac 2008
82197-202.
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Top Five Problematic Medication Classes leading
to ED
Oral Hypoglycemic

1. Hematologic
2. Endocrine agents
3. Cardiovascular agents
4. Central Nervous System Agents
5. Anti-infective

67
Oral Antiplatelet
Warfarin
Insulin
Budnitz et al. N Engl J Med 20113652000-12.2
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including time to benefit
Proportion in the PROSPER Trial with CHD Death,
Non-Fatal MI, or Stroke
PROSPER. Lancet 2002 360 162330.
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Osteoporosis
50 reduction in risk of fracture over a 3 year
period 1.2 absolute risk reduction for fractures
in 3 years
bisphosphonate
fracture-free
placebo
Time to benefit 9 to 18 mos
Median life expectancy 2.7- 4.7 years
Prevention of osteoporotic fracture
Benefits possibly similar in men, but data is
extrapolated from studies of women
TIME
National Osteoporosis Foundation. Clinicians
guide to prevention and treatment of
osteoporosis, 2009
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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

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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

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and patient capabilities

• 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 May47(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 200560A,2 Health Module
  217-223
• Medication Management Instrument for Deficiencies
  in the Elderly (MedMaIDE)
• Orwig D, Brandt N, Gruber-Baldini, A. Medication
  Management Assessment for Older Adults in the
  Community. The Gerontologist 200646661-668

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PUTTING IT ALL TOGETHER
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Inappropriate Prescribing

• Methods to Look at Inappropriate Prescribing
  e.g.
• American Geriatrics Society 2012 Beers 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.c
om/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) 46600-616.
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HISTORY AND DEVELOPMENT OF THE AGS 2012 BEERS
CRITERIA
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• Mark H Beers, MD
• 1954-2009
• 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 Harvards new Division on Aging
• Geriatric Fellowship, Harvard
• Faculty, UCLA/RAND
• Co-editor, Merck Manual of Geriatrics
• Editor in Chief, Merck Manuals

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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

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Specific Aims AGS 2012 Beers Criteria

• Specific aim update 2003 Beers Criteria using a
  comprehensive, systematic review and grading of
  evidence
• Strategy
• Incorporate new evidence
• Grade the evidence
• Use an interdisciplinary panel
• Incorporate exceptions

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Method

• Framework
• Expert panel
• 11 members
• IOM 2011 report on guideline development
• Includes a period for public comment
• Literature search

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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)

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Method

• Literature search ADE, inappropriate drug use,
  med errors, polypharmacy x age/human/English

25,549 citations 12/1/2001 3/30/2011
19,044 excluded
6,505 prelim review
4238 excluded
2,267 reviewed by co-chairs
Additional searches, additions
844 excluded
2169 reviewed
Additional searches, additions
258 included in evidence tables
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Method

• Survey to panel to rate (strong agree?strong
  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

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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 gt
  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

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

• Strength of recommendation
• Strong
• Benefits clearly gt risks and burden OR risks and
  burden clearly gt benefits
• Weak
• Benefits finely balanced with risks and burden
• Insufficient
• Insufficient evidence to determine net benefits
  or risks

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AGS 2012 BEERS CRITERIACLINICAL HIGHLIGHTS
EVIDENCE
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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
20031632716-2724 1 Hamilton H, Gallagher P,
Ryan C, Arch Intern Med 2011171(11)1013-1019 2
Rudolph J, Salow M, Angelini M et al. Arch Inern
Med 2008 168 (5) 508-513 3
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Beers Criteria- 3 Main Tables

• Table 2 Medications or medication classes that
  should be avoided in persons 65 years or older
• Table 3 Medications that should not be used in
  older person known to have specific medical
  diseases or conditions.
• Table 4 Medications that should be used with
  caution

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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

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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

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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.
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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.
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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 (gt90 days) Moderate Strong Allain 2005 Cotroneo 2007 Finkle 2011 McCrae 2007 Orriols 2011 Rhalimi 2009
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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
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Beers Criteria Table 3 Notables
Disease/Syndrome Drug/Drug Class Rationale
Heart failure NSAIDs and COX-2 inhibitors Nondihydropyridine CCBs (avoid only for systolic heart failure) Diltiazem Verapamil Pioglitazone, rosiglitazone Cilostazol Dronedarone Potential to promote fluid retention and/or exacerbate heart failure
Syncope Acetylcholinesterase inhibitors (CEIs) Peripheral alpha blockers Tertiary TCAs Chlorpromazine, thioridazine, and olanzapine Increases risk of orthostatic hypotension or bradycardia
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Beers Criteria Table 3 Notables
Disease/Syndrome Drug/Drug Class Rationale
History of falls or fractures Anticonvulsants Antipsychotics Benzodiazepines Nonbenzodiazepine hypnotics Eszopiclone Zaleplon Zolpidem TCAs 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 TCAs Anticholinergics Benzodiazepines Chlorpromazine Corticosteroids H2r receptor antagonists. Meperidine Sedative hypnotics Thioridazine 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.
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Beers Criteria Table 4 Notable Mentions
Drug Rationale Recommendation
ASA for Primary Prevention of cardiac events Limited data in individuals gt 80 Use with caution in adults gt 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
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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

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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

52
Resources Available Onlinewww.americangeriatrics.
org

• For the Health Professional
• Downloadable pocket card
• Evidence tables with links to supporting
  references
• Beers app AGS iGeriatrics
• For 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

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(No Transcript)
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Evidence Tables
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Patient Education
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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

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The Enhanced Monitoring Framework
Primary Concern
Patient Education and Activation Educate and
activate patient to understand and report
med-related problems
Complete Review Including meds
?Interactions

• Follow-up Prescribing Decision
• Maintain drug
• Change dose, frequency, form
• Discontinue
• Substitute
• Add new drug

Initial prescribing decision
Monitor -Side effects, effectiveness and
adherence -Assess if med still needed
?benefits/harms
Evidence and guidelines Prognosis
Patient preference and feasibility
Modified from Steinman MA et al. Beyond the
prescription Medication monitoring and adverse
drug events in older adults. JAGS.
201159(1)1513-20.
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Why is this important?

• Quality Metrics
• HEDIS http//www.ncqa.org/HEDISQualityMeasurement
  /HEDISMeasures/HEDIS2013/HEDIS2013FinalNDCLists.as
  px
• Improved patient care
• Decrease liability

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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.