Weighing The Risks and Benefits of Treatment in Older Adults

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Weighing The Risks and Benefits of Treatment in
Older Adults

• Do our scales need recalibration?
• Debra L. Bynum, MD
• Division of Geriatric Medicine
• University of North Carolina

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??????

• What do you think of when you think of
  Geriatrics

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Quips

• Benjamen Franklin
• All would live long, but none would be old
• Abraham Lincoln
• And in the end, its not the years in your life
  that count. Its the life in your years.

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Geriatric Domains

• Palliative Care
• Dementia
• Incontinence
• Falls
• Delirium
• Frailty
• Constipation

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Geriatric Catch Phrases

• Start low and go slow
• The Dying Patient. ?Moriatrics
• Life expectancy
• Quality of Life.
• Falls Risk.
• Polypharmacy

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Geriatric Realities

• Graying of America
• Increasing population of oldest of the old
  (number of people over age 80 will increase form
  6.9 million in 1990 to 25 million by year 2050)

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Geriatric Realities

• With an increase in older adults comes an
  increase in chronic diseases
• Many older adults are not dying but are living
  healthy, active lives with several chronic
  diseases

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New Geriatric Domains

• Myocardial Infarction
• Congestive Heart Failure
• Atrial Fibrillation
• Stroke
• Hypertension
• Hyperlipidemia
• Osteoporosis
• Aortic Stenosis

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Do we undertreat older adults with chronic
conditions?

• Probably Yes.

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Outline

• Why we might undertreat older patients
• Problems with clinical trials
• New perspectives on life expectency
• Examples
• Importance of Absolute Risk reduction and
  determination of baseline risk

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Objectives

• Appreciate the need to individualize care of
  older patients with complex medical problems
• Understand the importance of Baseline Risk in
  determining the overall impact, or absolute risk
  reduction, that any certain therapy may have
  patients at highest risk for a bad outcome stand
  to gain the most from a treatment that has even
  modest benefit!

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Why would we undertreat?

• Ageism
• Exclusion of older adults from clinical trials
• Assumption that the older adult may not want
  aggressive treatment
• Ideas based upon Life Expectancy
• Concern for Polypharmacy
• Concern that relative efficacies may be less for
  certain treatments in older subgroups
• Overestimation of Risks of Treatment and
  underestimation of Benefits of Treatment

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Ageism

• Coined 1969 by Dr. Robert Butler (first director
  of the National Institute on Aging)
• Systematic stereotying of and discrimination
  against people because they are old
• Fostered in clinical training
• Students and Residents see older adults from
  nursing homes and in the hospital
• The Aging Game
• The Unwritten Curriculum
• Age is NOT EQUAL to Frailty

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Exclusion of Older Adults from Clinical Trials

• 1/3 of all major, original research papers in
  1997 and 15 in 2004 excluded older people
  without justification
• Potential concerns
• More comorbid illnesses, more difficulty to
  follow, higher drop out
• Increased risks with treatment
• Polypharmacy
• Protocol restrictions on comorbidities
• Older population as vulnerable study group
• Barriers with transportation and mobility

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Assumption that Older Adult may not want
aggressive therapy

• Literature suggests that we tend to underestimate
  Quality of Life equivalents for others
• Data that physicians tend to assume that older
  adults do not want certain treatments, including
  ICU care, even though older patients, when asked,
  actually do want such care

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Ideas Based upon Life Expectency

• Average Life Expectancy can be misleading
• Overall average 77 years in 2002
• But, a 70 year old woman on average can expect to
  live another 18 years!
• 10 of 90 year olds will live to 100

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Polypharmacy

• Legitimate concern
• Medications seem to exponentially increase with
  each additional Diagnosis!
• Balance standard of care
• Risk for Adverse Drug Event directly related to
  number of medications
• Need to actively discontinue any unnecessary
  medications

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Some Examples

• Acute Coronary Syndrome
• Atrial Fibrillation and anticoagulation
• Lipid lowering therapy in older adults

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Common Theme

• Increasing age associated with increased bad
  outcome (stroke with afib, death/recurrent MI
  with acute coronary syndrome, cardiovascular
  event with hyperlipidemia)
• With increase in age, there is a decrease in the
  number of eligible patients who receive the
  standard of care treatment

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Acute Coronary Syndrome
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Eligible AMI patients given ASA in ED
(Annals Em Med 2005)
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Treatment with Aspirin

• Aspirin
• Same relative benefit in older patients
• Overall 20 lower death rate in patients who
  receive ASA after MI
• GREATER absolute benefit in older patients
  because of higher ABSOLUTE risk of bad outcomes
• ARR of death 4.5 in gt 65 vs 3.3 in those
  younger than 65

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given Beta Blockers in ED (Ann Em Med 2005)
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Eligible AMI patients given reperfusion (Ann Em
Med 2005)
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Who has an Acute MI? Numbers from the ED

• 8 younger than 50
• 15 50-59
• 20 60-69
• 30 70-79
• 22 80-89
• 5 gt90

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Ischemic Heart Disease in the Elderly

• Leading cause of death
• 35 of all deaths in people over age 65
• Among people who die of IHD, 83 are over age 65
• CV mortality and morbidity rates increase
  exponentially after age 75
• 6 US population over age 75
• 60 MI related deaths in people over age 75

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Pitfalls Trial Patients are Different

• Skewed Numbers in trials
• Patients over 85 2 of trial patients with ACS
  but for 11 of ACS events in community registries
• Older patients in trials are different than
  community elders who have Acute Coronary Events
• Older trial patients have lower traditional CV
  risk factors, less comorbidity, better
  hemodynamics, and better renal function than
  community elders with ACS AND than younger trial
  patients!

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Pitfalls Delay in Diagnosis

• Increased prevalence of Atypical symptoms
• Dyspnea, syncope, n/v
• Increased prevalence of acute heart failure
• Increased prevalence of nondiagnostic EKG
• 34 people over age 85 have baseline LBBB

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Risk Stratification

• Age is huge risk factor for bad outcomes (even
  when controlled for)
• ACC/AHA guidelines patients over age 75 are at
  high risk for death/recurrent MI
• Patients lt 65 with NSTE ACS have 1 hospital
  mortality
• Patients gt 85 have 10 hospital mortality with
  NSTE ACS
• Complications of recurrent MI, CHF, bleeding
  increase with age

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Atrial Fibrillation and Anticoagulation

• Prevalence 5 of people over age 65
• 10 of people over age 80
• 50 of all patients with afib are over age 80
• Dreaded outcome Stroke
• Strokes with afib have higher mortality/disability

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Age and Stroke Risk

• Incidence of Stroke with afib increases with age
• 1.3 /year in patients 50-59
• 2.2 /year in 60-69
• 4.2 /year in 70-79
• 5.1 /year in 80-89
• But it is much more complicated

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Predicting Risk of Stroke

• CHADS2
• CHF 1 point
• HTN 1 point
• Age over 75 1 point
• DM 1 point
• Prior Stroke/TIA 2 point
• Score 0 annual stroke risk lt1 (ASA alone)
• 2 or more annual stroke risk over 4 warfarin
• Score 1 individualized treatment decision
• Score 5 over 10/year stroke rate
• Score 6 over 15/year stroke rate

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Benefit of Warfarin

• Overall decreases risk of stroke by 60-70, ARR
  of 2.7-3 /year
• Beneficial in all age groups, even those over age
  75
• ?Quality of life of preventing a stroke

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Risks of Warfarin

• Risk of warfarin associated bleeding increases
  with age
• Risk ICH .34 /year in age less than 60, .76
  /year in those over 80
• Absolute risk of major bleeding 2.2 /year
  (increases to near 3 in those on warfarin plus
  asa)

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Warfarin use

• Older patients less likely to receive
  anticoagulation
• Older patients more likely to be
  underanticoagulated -- even though data is
  clear that there is no significant stroke
  protection at an INR of less than 2
• Overestimation of Falls Risk

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Warfarin in older patients Bigger Bang for the
Buck

• Patients under age 65 with afib and risk factors
  for stroke warfarin decreases risk of stroke
  from 4.9 /year to 1.7 /year
• In patients over 75 with risk factors (highest
  risk group), warfarin reduces risk of stroke from
  12 /year to 2-4 /year
• Those at highest risk for stroke (older, prior
  stroke, chf, dm, htn) are less likely to be given
  warfarin because of concerns for their
  comorbidities

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Lipid lowering therapy in older adults
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Lipid lowering therapy in High Risk Elderly
Patients (JAMA 2004)

• Retrospective cohort study
• Databases of over 1 million elderly in Ontario,
  study looked at nearly 400,000 over age 66 with
  history of CV disease or DM (SECONDARY
  PREVENTION)
• Outcome likelihood of statin use for each CV
  risk group

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Results

• Only 19 prescribed statins
• Likelihood of statin prescription was 6.4 lower
  for each year of increased age AND each 1
  increase in predicted 3 year mortality risk

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Likelihood of statin prescription Ages 66-74
Low CV risk (7.8 3 year mortality) Intermediate Baseline Risk (12.8 3 year mortality) High Baseline Risk (34.4 3 year mortality)
37.7 26.7 23.4
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Likelihood of statin Rx ages 75-80
Low CV risk (13.7 3 year mortality) Intermediate risk (21 3 year mortality) High risk (43 3 year mortality)
29 19 15
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Likelihood of statin Rx age gt 80
Low risk (25 3 year mortality) Intermediate risk ( 40 mortality) High risk (60 3 year mortality)
13 6 4
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Treatment-Risk Paradox

• Those at the highest risk of certain outcome (CV
  mortality) are often those NOT treated because of
  fear of risk of treatment
• Highest risk population may see the greatest
  ABSOLUTE benefit in reduction of events given the
  high baseline risk

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Importance of Absolute Risk Reduction and Number
Needed to Treat (NNT)

• NNT to prevent one patient from having event
• Clinically more meaningful than relative risk
• 1/ absolute risk reduction (example 10 ARR
  1/.10 NNT of 10)
• RRR of 50 may be good or not so good, depending
  on the number at risk
• Decrease events from 2 to 1 (ARR of 1)
• Decrease from 30 to 15 (ARR of 15)

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Risk Reduction

• In high risk populations, the BASELINE RISK has
  MORE impact than relative efficacy of a treatment
  on determining the absolute risk reduction and
  NNT

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Relation between baseline risk and NNT by various
relative efficacies of treatment (Alter, Am J Med
2004)
Age Group 1 year mortality NNT with relative efficacy of 10 NNT with relative efficacy of 25 NNT with relative efficacy of 50
lt50 2.3 437 175 87
50-64 4.8 209 84 42
65-74 11.1 90 36 18
gt74 27 37 15 7
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What does this all mean?
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Take Home Points

• Age is only one factor frailty and age are not
  the same
• There need to be increased numbers of older
  adults included in trials, and these patients
  should be of similar to older community patients
  and younger trial patients

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Take Home Points

• Care of complicated older patients with multiple
  chronic comorbidities must be individualized and
  cannot be totally driven by standard guidelines
• But guidelines and standards of care should not
  be ignored in patients just because they are older

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Take Home Points

• Weighing Risks and Benefits in treatment of an
  individual older patient requires
• Knowing risks and benefits of a therapy (not
  overestimating risk or underestimating benefit)
• Looking at the ARR and NNT
• Understanding the impact that Baseline Risk has
  upon absolute risk reduction
• Those at highest risk stand to gain the most
  and risk of treatment may be completely
  outweighed by this potential gain

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P.S.

• Case Study Just to complicate matters
• 85 healthy man with distant history of TURP and
  HTN was admitted 2 weeks prior with a NSTEMI that
  was uncomplicated he had early catheterization
  and a stent to his RCA, was placed on aspirin,
  clopidogrel
• He returned a few days later with a nosocomial
  pneumonia and atrial fibrillation, was started on
  warfarin. In the CCU, he had a foley catheter
  placed.
• He again returned a few days later with E coli
  UTI and sepsis syndrome
• He again returned a few days later with gross
  hematuria
• He stayed in the hospital for over a month with
  bleeding, urologic procedures
• ?Did he need the cath or intervention? The
  anticoagulation?