Download Weighing The Risks and Benefits of Treatment in Older Adults

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
??????
 What do you think of when you think of
“Geriatrics”?
Quotes
 Benjamin Franklin:

“All would live long, but none would be old.”
 Abraham Lincoln:

“And in the end, it’s not the years in your life
that count. It’s the life in your years.”
Geriatric “Domains”
 Palliative Care
 Dementia
 Incontinence
 Falls
 Delirium
 Frailty
 Constipation
Geriatric “Catch Phrases”
 Start Low and Go Slow…
 The Dying Patient “?Moriatrics”
 Life Expectancy
 Quality of Life
 Falls Risk
 Polypharmacy
Geriatric “Realities”
 “Graying” of America
 Increasing population of oldest of the old
(number of people over age 80 will increase from
6.9 million in 1990 to 25 million by 2050).
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.
New Geriatric Domains
 Myocardial Infarction
 Congestive Heart Failure
 Atrial Fibrillation
 Stroke
 Hypertension
 Hyperlipidemia
 Osteoporosis
 Aortic Stenosis
Do We “Undertreat” Older Adults with
Chronic Conditions?
 Probably Yes….
Outline
 Why we might undertreat older patients
 Problems with clinical trials
 New perspectives on life expectancy
 Examples
 Importance of Absolute Risk reduction and
determination of baseline risk
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!
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
Ageism
 Coined 1969 by Dr. Robert Butler (first director of
the National Institute on Aging)
 “Systematic stereotyping 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.
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
Assumption that Older Adult May Not
Want “Aggressive” Therapy
 The literature suggests that we tend to
underestimate “Quality of Life” equivalents for
others.
 There is data showing 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.
Ideas Based upon Life Expectancy
 “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
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
Some Examples
 Acute Coronary Syndrome
 Atrial fibrillation and anticoagulation
 Lipid lowering therapy in older adults
Common Theme
 Increasing age is 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.
Acute Coronary Syndrome
% Eligible AMI patients given ASA in ED
(Annals Emergency Medicine 2005)
100
90
80
70
60
50
40
30
20
10
0
<50
(n=169)
50-59
60-69
70-79
80-89
(n=461)
>90
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 > 65 vs 3.3 % in
those younger than 65
% Given Beta Blockers in ED (Annals
Emergency Medicine 2005)
80
70
60
50
40
30
20
10
0
<50
50-59
60-69
70-79
80-89
>90
% Eligible AMI patients given
reperfusion (Annals Emergency Medicine 2005)
90
80
70
60
50
40
30
20
10
0
<50
(n=62)
50-59
(n=96)
60-69
(n=107)
70-79
(n=117)
80-89
(n=69)
>90
(n=9)
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%
>90
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
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!
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% of people over age 85 have baseline LBBB
Risk Stratification
 Age is a 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 < 65 with NSTE ACS have 1% hospital
mortality.
 Patients > 85 have 10% hospital mortality with
NSTE ACS.
 Complications of recurrent MI, CHF, bleeding
increase with age.
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
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…
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 <1% (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
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
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)
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”
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.”
Lipid Lowering Therapy in Older Adults
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
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.
Likelihood of Statin Prescription:
Ages 66 – 74
Low CV Risk
Intermediate
Baseline Risk
High Baseline
Risk
(7.8% 3 year
Mortality)
37.7%
(12.8% 3 year
Mortality)
26.7%
(34.4 % 3 year
Mortality)
23.4%
Likelihood of Statin Rx:
Ages 75 – 80
Low CV Risk
Intermediate
Risk
High Risk
(13.7% 3 year
Mortality)
29%
(21% 3 year
Mortality)
19%
(43% 3 year
Mortality)
15%
Likelihood of Statin Rx:
Age > 80
Low Risk
Intermediate
Risk
High Risk
(25% 3 year
Mortality)
( 40% Mortality)
(60 % 3 year
Mortality)
13%
6%
4%
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.
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%)
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.
Relation between Baseline Risk and NNT by
Various Relative Efficacies of Treatment (Alter,
American Journal Medicine 2004)
Age Group 1 Year
Mortality
%
NNT with
Relative
Efficacy of
10%
NNT with
relative
Efficacy of
25%
NNT with
Relative
Efficacy of
50%
<50
2.3
437
175
87
50–64
4.8
209
84
42
65–74
11.1
90
36
18
>74
27
37
15
7
What Does this All Mean?
Take Home Points
 Age is only one factor; frailty and age are not the
same thing.
 There need to be increased numbers of older
adults included in trials, and these patients
should be similar to older community patients
and younger trial patients.
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.
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

Knowing that those at highest risk stand to
gain the most – and risk of treatment may be
completely outweighed by this potential gain.
P.S.
 Case Study: Just to complicate matters

85-year-old 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?