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Extrapolating general adult treatment principles to frail elderly populationsRebecca B. Sleeper, Pharm.D, FCCP, FASCP, BCPS
Associate Dean of Curriculum
TTUHSC School of Pharmacy
Objectives Compare and Contrast the treatment of
chronic disease in the general adult population as compared to frail elderly populations
Review the applicability of evidence based practice guidelines for the pharmaceutical management of common chronic diseases in elderly populations
State the importance of clinical judgment when making drug therapy decisions for various subgroups of elderly patients
Hypertension
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Adult treatment guidelines
JNC VII RecommendationsAll individuals over age 50 are
to be treated to the same treatment goals as the general population
A = B = C
A = B = CDrug Blood Cardiovascular
therapy pressure outcomes
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Subjects in JNC VII evidence base
TrialTotal number of subjects
Mean Age (years)
Systolic HTN in the elderly program (SHEP)JAMA 1991;265:3255-64
4736 72
Systolic HTN in Europe (SYST-Eur)Lancet 1997;350:757-64
4695 70
Swedish trial in old patients with HTN (STOP)Lancet 1991;338:1281-5
1627 76
Medical Research Council (MRC) trialBMJ 1992;304:405-412
4396 70
HTN outcomes among patients >60 years
Endpoint RR (95% CI)
Stroke 0.70 (0.59 – 0.82)
Coronary event 0.77 (0.66 – 0.90)
Cardiovascular death 0.82 (0.71 – 0.96)
All death 0.87 (0.68 – 0.98)
Staessen et al.
Subjects over age 80 in JNC VII evidence base
TrialTotal # of subjects
Mean Age (years)
Number of subjects
over age 80
Systolic HTN in the elderly program (SHEP)JAMA 1991;265:3255-64
4736 72 650
Systolic HTN in Europe (SYST-Eur)Lancet 1997;350:757-64
4695 70 441
Swedish trial in old patients with HTN (STOP)Lancet 1991;338:1281-5
1627 76 253
Medical Research Council (MRC)trialBMJ 1992;304:405-412
4396 70 0
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Young-old vs. Old-old
0
10
20
30
40
50
60
70
80
90
80 100 120 140 160 180 200
Systolic BP (mmHg)
Pro
bab
ilit
y o
f m
ort
alit
y (%
)
Age 65-84 Age >85
J Am Geriatr Soc 2001;49:367‐74
HTN and survival in elderly men
Men age 65 - 84
0
20
40
60
80
100
1 2 3 4 5 6
Follow-up (years)
% s
urv
ived
SBP <130SBP 130-179SBP >180
Men age > 85
0
20
40
60
80
100
1 2 3 4 5 6
Follow-up (years)
% s
urv
ived
SBP <130SBP 130-179SBP >180
J Am Geriatr Soc 2001;49:367‐74
HTN and survival in elderly women
Women age 65 - 84
0
20
40
60
80
100
1 2 3 4 5 6
Follow-up (years)
% s
urv
ived
SBP <130SBP 130-179SBP >180
Women age > 85
0
20
40
60
80
100
1 2 3 4 5 6
Follow-up (years)
% s
urv
ived
SBP <130 SBP 130-179
SBP >180
J Am Geriatr Soc 2001;49:367‐74
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Rastas et al. 2006
Evaluated relationship between BP and survival in individuals >85 521 fully evaluated for 9 year period Risk of death highest among individuals
with SBP < 140/90 ▪ (HR=1.35, 95%CI 1.04-1.74, p=0.02) No relationship between use of blood
pressure lowing medications and death▪ (HR 1.16, 95%CI 0.92-1.45)
Rastas et al. JAGS 2006;54:912‐918
INDANA (all subjects > age 80)
Endpoint RR (95% CI)
Stroke 0.64 (0.40 – 0.89)
Coronary event 0.85 (0.48 – 1.32)
Cardiovascular death 1.11 (0.87 – 1.41)
All death 1.14 (1.00 – 1.31)
Gueyffer et al.
Hyvet pilot (all subjects > age 80)
Endpoint HR (95% CI)
Stroke events 0.47 (0.24-0.93)
Stroke mortality 0.57 (0.25-1.32)
Total mortality 1.23 (0.75-2.01)
J Hypertens 2003;21:2409‐2417
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Evidence of goal BP?
TrialMean Entry BP
(mmHg)Mean Treatment
BP (mmHg)
Systolic HTN in the elderly program (SHEP)JAMA 1991;265:3255-64
170/77 143/68
Systolic HTN in Europe
(SYST-Eur)Lancet 1997;350:757-64
174/86 151/79
Swedish trial in old patients with HTN (STOP)Lancet 1991;338:1281-5
195/102 167/87
Medical Research Council (MRC) trialBMJ 1992;304:405-412
185/91 152/78
Drug therapy choicesTrial Primary treatment regimen
SHEPChlorthalidone, atenolol,
reserpine
SYST - EurNitrendipine, enalapril,
hydrochlorothiazide
STOPHydrochlorothiazide/amiloride, metoprolol, atenolol or pindolol
HYVET Pilot Bendroflumethiazide, lisinopril
HYVET Indapamide SR, perindopril
HYVET (Full study)
3845 subjects aged >80 years Indapamide (+/- perindopril) vs placeboMean baseline BP 173/91mmHg Treatment goal 150/80mmHg
30% reduction stroke (both fatal/nonfatal) 39% reduction in death from stroke23% reduction in cardiovascular death21% reduction in death from any cause64% reduction in heart failure
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HYVET conclusions
First prospective study to show mortality benefit associated with BP reduction among very elderly Study was stopped early due to the mortality
benefit Benefit was associated with ▪ a more conservative blood pressure goal▪ Thiazide diuretic
Caveats Very healthy, ambulatory, community dwelling
elderly with few co-morbidities▪ Co-morbid diabetes only about 7%, incidence
of other cardiovascular co-morbidities also all under 10%
Updated guidelines
JNC VIII “Older patients” now defined
as >60 years New BP goal of 150/90mmHg However, if an individual has attained a blood pressure less than 150/90mmHg and is tolerating therapy, no need to withdraw therapy
JAMA, published online Dec 18, 2013
Unanswered questions
Individuals with Stage I HTN?
Individuals with cardiovascular co-morbidities?
What is the importance of 24-hour BP control?
What is the importance of Pulse Pressure?What is the best blood pressure for the
brain?
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24-control
Staessen et al. JAMA 1999 (sub-group analysis of Syst-Eur)
A 10mmHg increase as measured by CABP, but not conventional method, predicted CV mortality: HR 1.34 (95%CI 1.30-1.75), and
A 10% increase in night:day BP ratio more accurately predicted CV event risk: HR 1.41 (95%CI 1.03-1.94)
Orthostatic hypotension
>20mmHg fall in systolic BP associated with symptoms of dizziness and lightheadedness
Incidence does not correlate with all types of antihypertensive medications
Risk increases with elevations in BP, particularly before breakfast evaluations
Lowest after lunch
Ooi et al. JAMA 1997
Pulse Pressure
INDANA 2002
10mmHg wider PP at baseline corresponds to a 6% (p=0.001) increase in mortality
Vaccarinoet al. 2001
10mmHg increase in PP associated with 32% increase in HF and 24% increase in stroke
Staessenet al. 2002
24h and nighttime PP predicted total mortality, CV mortality, and all CV events. Conventionally measured PP predicted CV mortality
Weiss et al. 2009
PP >62.5mmHg associated with higher risk of mortality (HR = 1.69, 95% CI 1.19-2.38, p = 0.003)
140/90 = PP 50mmHg150/80 = PP 70mmHg
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Launer et al. 2000
Increased risk of dementia among untreated men >65 years with BP >160/95mmHg
Kivipelto et al. 2001
SBP >160mmHg associated with higher risk of dementia vs 140mmHg (OR 2.8 95%CI 1.1-7.2)
Wu et al. 2003
BP >160/95 associated with increased risk of dementia 15 years later (OR 2.0 95% CI 1.1-3.5)
Whitmer et al. 2005
Self-reported HTN or measured BP >140/95mmHg associated with dementia (HR 1.24 95%CI 1.04-1.48)
HTN in mid life and dementia
Among strata of subjects with SBP >160/90mmHg:Risk of all-cause dementia was
increased among youngest age group: HR 1.6; 95% CI 1.01–2.55
Magnitude of risk declined with age for oldest age group (>85 years): HR 0.64; 95% CI 0.32–1.30
Outcomes among age groups
Li et al. JAGS;2007
Guo et al. 1996
BP <140/75 associated with higher incidence of dementia
Morris et al. 2000
BP <130/70mmHg associated with higher incidence of Alzheimer’s Disease
Morris et al. 2001
SBP >160 vs <140mmHg: OR for dementia with High SBP 0.29 (95% CI 0.10 - 0.86).
Ruitenberget al. 2001
BP inversely related to Dementia risk among patients on HTN medications
Verghese et al. 2003
DBP <70 vs >90mmHg: RR for dementia with Low DBP 2.1 (95%CI 1.1 - 3.8).
Nilsson et al. 2007
Low SBP and DBP associated with cognitive decline.
Hypotension and Dementia
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HTN Conclusions – what we’d like to see in the consensus recs For relatively healthy, young-old
(65-80 years) patients general adult treatment guidelines apply
For old-old (>80 years) patients with relatively uncomplicated HTN, HYVET data can be applied General BP target of 150/80mmHg Strongest evidence among
individuals with Stage II BP or pulse pressure >60 using thiazidediuretic
HTN Conclusions Treatment of patients with complex co-
morbidities requires a judgment call – decisions often based on the principle of “treat the biggest threat”
Language about blood pressure’s relation to cognitive function still lacking in the guideline “Brain health” should be among the counseling points
when educating patients about the preventative benefits of treating HTN in mid-life or in the young-old years
Aggressive BP lowering may worsen cognition among frail patients with established dementia.
Sample Patient
86 year old community dwelling male patient
PMH: TIA (on aspirin therapy), declining renal function
Vitals: BP 172/89mmHg, HR 84
CrCl: 35 ml/min
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Sample Patient
90 year old community dwelling female patient
PMH: non-significant Vitals: BP 152/89mmHg, HR 84
CrCl: 80ml/min
Sample Patient
86 year old community dwelling male patient
PMH: TIA (on aspirin therapy), declining renal function, and Type 2 diabetes
Vitals: BP 172/89mmHg, HR 84
CrCl: 35 ml/min
Sample Patient
86 year old institutionalized male patient
PMH: Alzheimer’s disease, declining renal function
Vitals: BP 172/89mmHg, HR 84
CrCl: 35 ml/min
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Sample Patient
86 year old institutionalized female patient
PMH: Alzheimer’s Disease, HTN, declining renal function
Current medications: Clonidine 0.2mg BID
Vitals: BP 108/56mmHg, HR 84 CrCl: 35 ml/min
Hyperlipidemia
Adult treatment guidelines
ATP III RecommendationsOlder persons who are at
higher risk and in otherwise good health are candidates for cholesterol-lowering therapy
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Defining the subgroups:
Primary vs. Secondary treatment
Age ranges<65 years
“Young old” >65 years“Middle old” >70-75 years
“Old-old” >82 years Healthy / good prognosis vs. frail / poor
prognosis Pre-existing dementia
Secondary Prevention TrialsStudy Mean Age
(years)>65 YO RRR% ARR% NNT
SSSS 1994 58 51% 29 3.3 29
CARE 1996 59 51% 23 3.0 34
LIPID 1998 62+ 39% 23 1.9 52
HPS 2002 64 47% 12 1.8 58
PROSPER*2002
75 100% 20 4.3 24
ASPEN* 2006 63 46% 15 4.6 22
CORONA 2007
73 41%# 6 1.8 56
*Subjects with previous vascular history; + median; # Subjects over 70 years oldMangoni AA, Jackson SHD, Br J Clin Pharmacol, 2006; Graphpad software; Kjekshus J, et al. NEJM, 2007
Primary Prevention TrialsStudy Mean Age
(years)>65 YO RRR% ARR% NNT
AFCAPS/ TexCAPS 1998
58 21% 37 2.0 49
ALLHAT-LLT 2002
66 55% 11 1.1 91
PROSPER 2002
75 100% 17 2.1 47
ASCOT-LLA 2003
63 64% 36 1.1 94
MEGA 2006 58 10-13%+ 33 0.8 120JUPITER 2008
66 * -- 43 1.2 82
Ali R & Alexander KP, AJGP, 2007; Ridker PM et al, NEJM, 2008; Nakamura H et al, Lancet 2006*Median value reported; +estimated
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Primary Prevention Trials-Diabetes
Study Mean Age
(years)
>65 YO
RRR% ARR% NNT
HPS 2003
-- 28% 20 5.6 18
CARDS 2004
61.5 50% 30 4.0 25
ASPEN* 2006
60.5 33% 5 0.4 282
Ali R & Alexander KP, AJGP, 2007; Knopp RH et al, Diab Care, 2006
*Primary prevention subjects only
PROSPER—Landmark Elderly Study
5,804 subjects (mean 75 years old)With CVD or at high CVD risk; LDL mean 147mg/dL
Pravastatin 40mg vs Placebo Follow-up 3.2 years
Endpoint of CHD death, MI, and stroke
Reduced incidence of endpoint 0.85 (CI 0.74-0.97) No diff. in total mortality, myopathy or liver dysfunction
Higher incidence of GI cancers with pravastatin
Failed to show a reduction in risk for stroke
Shepherd, Lancet 2002
CORONA—No Benefit in HF
5,011 subjects at least 60 YO with systolic heart failure (Class II-IV) Mean age 73 years 41% over 71; 11% over age 77
Rosuvastatin 10mg or placebo; F/U: 3 years
No benefit of treatment on primary or secondary outcomes
Kjekshus, NEJM, 2008; Capurso, JAGS 2008
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JUPITER Trial—CRP Biomarker
Prevention of vascular events in subjects with hs-CRP > 2.0mg/L 17,802 subjects; Median age 66 years
(Interquartile range of 60-71years) Stopped trial early at 1.9 years due to
benefit in reduction of vascular events (HR 0.56, CI 0.46-0.69)
Subgroup analysis: 9,261 subjects 65+ years old not significantly different
Ridker 2008
Statin Efficacy Evidence Recap
Young OldMultiple studies support use for
primary and secondary prevention of cardiovascular disease
Old/Middle OldEvidence mixed, but generally
supports use in secondary prevention
Oldest Old—Evidence is lacking
Other Lipid Lowering Therapies
Cholestyramine-LRC-CPPT Nicotinic Acid 30 studies, pooled mean age 58
years Only 2 studies included > 65 years old
Only 1 study with CV outcomes Age range was 30-64 years
Birjmohun, JACC 2005
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Fibrates in Older Adults
Ciprofibrate, Clofibrate, Fenofibrate, Bezafibrateand Gemfibrozil (53 studies)
Pooled mean age 58 years16,802 subjects total, 5.8% female
RRR 25% (CI 11-37%)NNT to prevent 1 coronary event
= 33 for 4 years= 100 to prevent 1 CV death
Evidence limited to younger cohort at this time
Birjmohun, JACC, 2005
Adverse Effects
Common:Headache 9-17%Dyspepsia 8%Diarrhea 5%Abdominal pain 5%Myalgia 5%Fatigue 3%Insomnia 3%Nausea 3%
SeriousHepatotoxicityRhabdomyolysis
Others Important in Older PatientsCognitionCancer
Risk Factors for Statin Myopathy
Patient Factors
Advanced age
Female sex
Renal insufficiency
Polypharmacy
Hypothyroidism
Diet (grapefruit juice)
Statin Properties
High systemic exposure
Lipophilicity
High bioavailability
Limited protein binding
Potential for drug-drug interactions
Rosenson, Am J Med, 2004
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Risk Factors for Elevations inStatin Serum ConcentrationsAdvanced age and frailtySmall body frameDeteriorating renal functionInteracting drugsInfectionUntreated hypothyroidismPeri-operative periodsAlcohol abuse
McKenney 2006
Cancer Evidence PROSPER-increased GI cancers
Meta-analyses >86,000 subjects: Cancer incidence
(OR, 1.02; 95% CI, 0.97-1.07) or cancer deaths (OR, 1.01; 95% CI, 0.93-1.09)
>90,000 subjects: There was no evidence that statins increased the incidence of cancer overall (1.00, 0.95-1.06; p=0.9)
Baigent, Lancet, 2005; Dale, JAMA, 2006
Updated guidance
Older subgroup is defined as >75 years
Primary prevention: Poor data to support initiation of therapy
Secondary prevention: Data supports moderate intensity statin
therapy.
Poor data to support high intensity statin therapy
Do not need to withdraw established therapy if tolerated
Stone et al. ACC/AHA published online November 12, 2013
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Algorithm for Statin UsePatient’s life expectancy > 3‐5 years?
Secondary or Primary Prevention?
Secondary Prevention: Start moderate statin
Primary: Poor data, considerPatient Goals,Venue, Cognition
Assess Cardiovascular Risk with Non‐invasive testing
Assess Risk for Adverse Drug Effects
Primary Prevention in Healthy, Informed Elderly Patient: Start moderate statin
Sample Patient
86 year old community dwelling male patient
PMH: TIA (on aspirin therapy), declining renal function
Vitals: BP 172/89mmHg, HR 84 – (HCTZ 25mg has been initiated)
CrCl: 35 ml/min LDL: 127
HDL 32
Sample Patient
90 year old community dwelling female patient
PMH: non-significant Vitals: BP 152/89mmHg, HR 84
CrCl: 80ml/min LDL: 144
HDL:62
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Sample Patient
86 year old institutionalized male patient
PMH: Alzheimer’s Disease, h/o TIA Current medications, Aricept 10mg HS,
Namenda 10mg BID, Crestor 20mg QD
Vitals: BP 148/87mmHg, HR 84 LDL: 68
HDL:38
Sample Patient
82 year old institutionalized female patient
PMH: CAD, A-Fib, history of stroke Current medications: Metoprolol 100mg
BID, lisinopril 5mg QD, warfarin 4mg daily (INR stable)
Vitals: BP 144/78mmHg, HR 68, weight 92lb (under IBW)
LDL: 118
HDL: 38
Heart Failure
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Heart failure (HF) Changes in anatomy and physiology of the
cardiovascular system contribute to the incidence of heart failure in older patients:
Increased systemic vascular stiffness, with impaired diastolic relaxation and compliance Increased ventricular afterload
Diminished responsiveness to beta-adrenergic stimulation Higher plasma concentrations of catecholamines,
but less responsive to these Impaired mitochondrial energy production in
response to stress Decline in sinus node function Impaired endothelial function
EpidemiologyThe incidence of heart failure
increases with age. 9.3% in men and 4.8% in women
between the ages of 60-79 years13.8% in men and 12.2% in
women greater than age 80The incidence of mortality
associated with heart failure is also higher in the geriatric population.
Clinical presentation
Adult / typical
Shortness of breath, angina, chest pain
Older adult / atypical Subjective complaints of
symptoms as anorexia, confusion, generalized weakness, and fatigue
B-type natriuretic peptide (BNP) can be difficult to accurately interpret, as BNP concentrations tend to be higher in the elderly Unclear if different “normative”
values should be established for frail populations
Cough or non-specific respiratory symptoms can be the primary or, often, ONLY presenting complaint May be confused with respiratory
conditions such as COPD, asthma, or infection such as bronchitis or pneumonia
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Other diagnostic considerations Leg Edema
Common but not universal, more nonspecific in elderly Fatigue
Aging, depression, beta blocker use, over diuresisWeight gain/loss
Depression, dementia (weight loss) Syncope
Orthostatic hypotension, in particular postprandial hypotension
Change in mental status Common if very old/frailOften accompanied by dyspnea or fatigueMore common if vascular dementia and less common if
euvolemic without dyspnea or fatigue
How well do the guidelines apply to the real world?
Randomized Controlled Trials
Real World
Mean age 60 70
Prevalent gender Male Female
LVEF > 40% Generally excluded 40-60%
Co-morbidities Excluded Frequent
Drug titration To target Low
Compliance High Low
1-year mortality < 15% 25-30%
Differences between populationsYounger
Patients
Elderly
Patients
Prevalence Low High
Prevalent Gender Male Female
Etiology Ischemia Hypertension
LVEF Reduced Normal
Co-morbidities Rare Common
Therapy Based on RCTs Empirical
Clinical Trials Many Few
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Characteristics of older vs. younger patients
Age ≥ 80 years
(n = 741)
Age < 80 years
(n = 2836)
P-value
Age (years) 83.7 68.4 <0.001
Male Gender 44% 66% <0.001
ComorbiditiesCHD 51% 54% 0.094
HTN 67% 61% 0.003
Atrial fibrillation/SVT 48% 36% <0.001
Diabetes 29% 34% 0.017
Stroke/TIA 20% 12% <0.001
Anemia 47% 37% <0.001
Presenting factors
Systolic BP (mmHg) 140 130 <0.001
Somnolence/confusion 24% 14% <0.001EHFS II: Eur Heart J 2009; 30:478-86
Continued…
Age ≥ 80 years
(n = 741)
Age < 80 years
(n = 2836)
P-value
Laboratory parameters
GFR < 60 mL/min 73% 53% <0.001
GFR < 30 mL/min 16% 10% <0.001
Echocardiography
LVEF (%) 40 35 <0.001
LVEF > 45% 39% 28% <0.001
Mod-Severe AS 16% 7% <0.001
Coronary angiography
No CAD 19% 32% 0.004
EHFS II: Eur Heart J 2009; 30:478-86
Older patients in clinical trials
Drug Class Trial Elderly(years)
Mean age(years)
Beta-blockers COPERNICUS
US Carvedilol
CIBIS II
MERIT-HF
BEST
SENIORS
> 65
> 59
> 71
> 60
> 65
> 75
63
58
61
64
60
76
ACE inhibitors SOLVD
ATLAS
> 61
> 70
61
64
ARBs CHARM-Added
Val-HeFT
--
> 65
64
63
ARAs RALES > 67 65
Digoxin DIG > 70 63
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Beta blockers
Subgroup analysis of MERIT-HF (Metoprolol)Patients ≥65 years (average age 72 years)
had significant reductions in all- cause mortality (37%), sudden death (43%), and hospitalization (36%)
However, patients >65 years received lower doses than younger patients (146mg vs. 168mg) and were more likely to discontinue therapy with metoprolol
Significantly fewer older patients received ACE inhibitors
More older patients had atrial fibrillation or were s/p MI
Beta blockers (prospective, older cohort)
SENIORS trial (Study of the Effects of nebivololIntervention on Outcomes and Re-hospitalization in Seniors with Heart Failure)
Nebivolol vs. placebo in patients ≥70 years (mean age 76) with heart failure, regardless of left ventricular ejection fraction
Significantly fewer patients in the nebivololgroup reached the primary outcome of all-cause mortality or cardiovascular hospital admission. There were no differences in hospital admissions.
ACE inhibitors Systematic overview ACE inhibitors in five large
trials including 12,763 patients, mean age 61 years Incidence of mortality was lower (23% vs. 26.8%) in ACE inhibitor
group Incidence of readmission for HF was lower in the ACE inhibitor group
(13.7% vs. 18.9%) Subgroup analysis by age: smaller mortality benefit in patients age
>75
Retrospective study of nursing facility residents receiving ACE inhibitors or digoxin, average age 85 years (HF type not distinguished) ACE inhibitor use (dose not standardized) associated with lower
risk of mortality compared to digoxin (0.89, 95% CI 0.83-0.95) Non-significant trend toward a reduction in hospitalization
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ARB’s
No specific evidence in very elderly but may be tried in patients who do not tolerate ACE inhibitorsRecommendation is primarily
empiric / based on subgroup analysis of trials in younger patients
Digoxin Digoxin Investigation Group (DIG) study
2,092 patients between the ages of 70-79 and 425 patients 80 years of age and older
Outcomes assessed across age stratamortality, hospitalizations for heart failure, hospitalization for digoxin
toxicity, and withdrawal of digoxin
Reduction in hospitalization was independent of age However hospitalization from digoxin toxicity or digoxin withdrawal
was higher among older cohort No reduction in incidence of mortality
Digoxin is only appropriate for systolic heart failure Some studies have demonstrated a lower target range
for serum digoxin concentrations of 0.5-0.8 ng/mL
SpironolactoneNo specific elderly dataRecommendations are empiric or
based upon subgroup analysis of trials in younger patients
No data for HF with preserved left ventricular function
Older patients may be more vulnerable to electrolyte disturbances
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Overall evidence level< 75 years > 75 years
Reduced Systolic Function (LVEF < 40%)
ACE inhibitors Excellent Fair a,b
ARBs Excellent Fair a
Beta-blockers Excellent Good a,b
ARAs Good Fair a
Preserved Systolic Function (LVEF > 40-50%)
ACE inhibitorsc Fair d Fair
ARBsc Fair d Lacking
Beta-blockers Fair a Fair
ARAs Lacking Lacking
a Subgroup analysis. b Retrospective analysis of large cohorts. c Primarily reduction in HF re-hospitalization. d Evidence from one RCT w/ limited positive effects.
BNP guided therapy? TIME-CHF – 499 patients
Intensive management vs. standard (BNP-guided therapy with symptom guided therapy)“Young group” mean age 69 , “Old group” mean age 82
BNP-guided therapy was more aggressive –higher doses of ACE inhibitors and β-blockers No significant difference in the primary outcomes
(hospitalization-free survival and quality of life)
Subjects 60-74 years benefited more from BNP-guided therapy, subjects >75 years did not achieve benefit and instead there was a trend toward increased harm
Nursing facility studies Thirteen studies between 1991-2002 ACE inhibitors (n=9 studies), digoxin
(n=4), and diuretics (n=7) ACE inhibitors
Underused, prescribed at inefficient doses Used more often in “young” elderly (65-74 yrs)
than “old” elderly (> 85 yrs)
Digoxin - inappropriately indication (e.g. no documented atrial fibrillation, NSR)
Diuretics - monotherapy common, inclusion criteria for ARA use not followed
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Overview: Drug therapy challenges in older patients
Lack of RTC evidence in oldest groups Atypical disease presentation Comorbidities, Drug-drug interactions Ability to tolerate medications
More sensitive to bradycardia with beta blockers More vulnerable to volume depletion with diuretics More vulnerable to hyperkalemia with ACE inhibitors Increased t ½ and risk of toxicity associated with digoxin
Undertreatment / inappropriate treatment More likely to receive diuretic monotherapy Digoxin without appropriate indication is common May receive respiratory interventions for wrong diagnosis
Sample Patient
86 year old community dwelling male patient
PMH: Heart Failure with preserved LVEF Current medications: Lisinopril 20mg BID,
furosemide 20mg daily, KCL 10mEq daily, aspirin 31mg daily
Vitals: BP 108/68mmHg, HR 90
Sample Patient
80 year old community dwelling female patient
PMH: HF with preserved LVEF Current medications: enalapril 5mg QD,
metoprolol 12.5mg BID
Vitals: BP 172/89mmHg, HR 94 CrCl: 35 ml/min
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Sample Patient 86 year old institutionalized male patient
PMH: COPD, Heart failure
Current medications: Advair 1puff BID, Lasix 80mg BID, KCL 40mEq QD, Digoxin 0.125mg, O2 PRN
Vitals: BP 172/89mmHg, HR 84
Labs Na 138, K 3.4, Cl 99, CO2 25, BUN 44, SCr 1.1, Gluc 99
CrCl: 35 ml/min
HPI: Recent cough, complains of malaise
Chest x-ray nonspecific
New orders: Levofloxacin 750mg QD (3rd course of antibiotics in 4 months)
Diabetes mellitus
Prevalence
• Estimated– 26.9% of those 65 and older have Type
2 diabetes• Older individuals with DM type 2 are at
greater risk of problems than age-matched elders without diabetes– Premature death, functional disability,
HTN, CAD, stroke, depression, cognitive impairment, urinary incontinence, injurious falls and persistent pain
Centers for Disease Control and Prevention National Diabetes Fact Sheet. From: http://www.cdc.gov/diabetes/pubs/pdf/ndfs_2011.pdf. Accessed: 4/2/13.
Brown AF, et al. J Am Geriatr Soc. 2003;51:S265‐S280.
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Age related changes in endocrine and renal function
Insulin concentrations increase with age
Possibly related to relative increase in total body fat vs lean muscle
Increased peripheral tissue resistance to insulin
Reduction in renal function will alter the elimination half life and/or side effect risk of drug therapy
Lamberts et al. Science 1997
Considerations in elderly patients
Presentation
Increased renal threshold for glucose increased
Decreased thirst drive
Decreased awareness of hypoglycemia, especially with cognitive impairment or medications that mask symptoms
Diagnostics and monitoring
Reliability of Hemoglobin A1c in setting of decreased RBC or Hgb
Finger sticks can present quality of life challenge, especially with cognitive impairment
Evidence-base recommendations
Glycemic targets
7% vs. 8%?
Consider frailty, prognosis (less than 5 years to live)
No clinical trial data on macro or micro consequences of intensive glycemic control in older adults
Comorbidity management:
Simultaneous intensive management of all disease states may not be possible/feasible
Use of aspirin
81 mg daily in those not on other anticoagulant therapy and with no contraindications to aspirin
Brown AF, et al. J Am Geriatr Soc. 2003;51:S265‐S280.ADA Diabetes Care. 2013:36(1 Supp):S11‐S66.
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Major clinical trial evidence
ACCORD Enrolled seniors up to 79 years Average age: 62 No break down of elderly versus non-elderly Intensive tx to goal A1c < 6% showed
increased mortality/CV events
ADVANCE All over age 55; average age 66 yearsMicro and macro vascular complications Decrease in nephropathy in intensive-mgmt
The Action to Control Cardiovascular Risk in Diabetes Study Group. N Engl J Med. 2008;358:2545-2559.The ADVANCE Collaborative Study Group. N Engl J Med. 2008;358:2560-2572.
What is evidence base lacking?
Specific outcome data describing association of glycemic control with “other” clinical endpoints
Wounds Infections
Cognition
Hypoglycemia
Atypical manifestations
Can occur even with increased A1c…40 community-dwelling seniors aged 69 or
older
All with A1c ≥ 8%Continuous-glucose monitoring x 3 days
65% with at least 1 hypoglycemic readingAverage – 4 hypoglycemic events
Out of 102, 95 unrecognized by symptoms
Munshi MN et al. Arch Intern Med. 2011; 171:362‐4.
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Hypoglycemia and dementiaStudy OutcomeWhitmer, RA. JAMA 2009
Elderly patients with type 2 diabetes and history of severe hypoglycemic episodes had a greater risk of dementia
Feinkohl I. Diabetes Care 2013
Severe hypoglycemia associated with accelerated cognitive decline
Lin CH. J Intern Med 2013
Adult diabetic patients with prior hypoglycemia had a significantly increased risk of dementia
Yaffe K. JAMAIntern Med 2013
Those who experienced a hypoglycemic event had a 2-fold increased risk for developing dementia. Older adults with DM who developed dementia had a greater risk for having subsequent hypoglycemia
Bruce DG Diabetologia 2009
Dementia is a risk factor for hypoglycemia
Hyperglycemia Elderly patients with Type 2 Diabetes usually do not
present in DKA, but Hyperosmolar Hyperglycemia Non-ketotic Syndrome (HHNS) is more common
Incidence peaks in 7th decade, risk higher with dementia or during pneumonia
Often unrecognized or symptoms misattributed to something else
Severe hyperglycemia
Dehydration (with increased serum osmolality)
Severe osmotic diarrhea
May co present with confusion and pancreatitis
Treated with regular insulin and fluid replacement
Select oral agents
• Sulfonylureas– Glyburide– Glipizide– Glimiperide
– Are they even a candidate? – MOA of drug class is poor match for
mechanism of disease at this age– Hypoglycemia risk
– Renal issues/Liver issues– Avoid with insulin!
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Select oral agents
• Thiazolidinediones– Edema– CHF– Cost– Additional monitoring
• Alpha-glucosidase inhibitors– GI issues/Tolerability
• Especially pertinent in those with weight loss (NH)– Timely dosing within NH setting
• Needs to be given with meals• Hypoglycemia management
• Glucose vs. Sucrose
Select oral agents• Metformin – MOA is a better match to mechanism of disease
– Renal recommendations• SCr:
• 1.5 mg/dL for men, 1.4 mg/dL for women• CrCl:
• Original recommendations state avoid if < 60 mL/min• Modified recommendations suggest ClCl down to 30ml/min
acceptable• Age recommendations
• Age greater than 80 historically a relative contraindication, may be ok if safety parameters are met
• If 80+ or reduced muscle mass, timed urine collection to estimate CrCl
– Radiographic procedures – consideration for any age group– Pill size/Smell
• Those with swallowing difficulties• B12 deficiency
Select oral agents Meglitanides
HypoglycemiaAlthough less than SFU
Cost Incretin-mimetics
Cost Exenitide, Liraglutide, Pramlintide
HypoglycemiaDosing (within 60 minutes of a meal)Renal dysfunction
Sitalgliptin, Saxagliptin, LinagliptinRenal dysfunction
Limited data in advanced age groups
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Select Agents: Insulin Insulin
Initial dosing Adjustments based on blood sugar readings
Renal dysfunction Hypoglycemia Perceptions
Cause/Effect vs. Last-line or “Last-ditch” intervention
“Safer” insulin? (Next slide) Patient-related variables
Select agents: Insulin Is there a preferred insulin?
Papa, et al.
Insulin glargine vs. Increased dose of oral agentsA1c reduction of 1.5% vs. 0.6% (respectively)
Fewer total hypoglycemic events in insulin glargine group (23 vs. 79 p = 0.03)
Less likely to experience hypoglycemia (33.3% vs. 60.7% p=0.04)
Dornhorst, et al.Observational study of adding insulin detemir
Decreased A1c by 0.7%
Decreased hypoglycemic events when compared to prior to starting insulin detemir
Papa G et al. Acta Diabetol. 2008; 45:53‐9.Dornhorst A et al. Diabetes. 2007; 56(Suppl 1):A557.
Recommendations In frail older adults, those with less than 5 years to live and
in those whom the risks outweigh the benefits, less stringent glucose control, including a target hemoglobin A1c of < 8% is appropriate.
Remember A1c can be inaccurate though
Diet and lifestyle recommendations must be appropriate to setting and functional level
Avoidance of hypoglycemia becomes an increasing focus
Risk of cognitive impairment
Metformin is a first line choice unless CrCl <30ml/min
Insulin therapy may be preferred add-on if patient can manage it
Severe hypoglycemia may present as HHNS
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Sample Patient
86 year old community dwelling male patient
PMH: TIA (on aspirin therapy), declining renal function and Type 2 Diabetes
Vitals: BP 172/89mmHg, HR 84
CrCl: 45 ml/min HbA1c: 8.8%
Fasting BG: 130-158 Postprandial BG: 180-302
Sample Patient
86 year old community dwelling male patient
PMH: TIA (on aspirin therapy), declining renal function, Type 2 diabetes
Current medications: glyburide 5mg BID
Vitals: BP 172/89mmHg, HR 84
CrCl: 35 ml/min
HbA1c: 8.8%
Fasting BG: 130-158
Postprandial BG: 180-302
Provider wants to add insulin
Sample Patient
86 year old community dwelling male patient
PMH: Mild Cognitive impairment, Type 2 diabetes
Current medications: Lantus 18U HS, Regular insulin 4U with each meal
HbA1c 6.9% Blood glucose log: unavailable
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Sample Patient
86 year old institutionalized female patient
PMH: Alzheimer’s Disease with behavioral disturbances, Type 2 diabetes
Current medications: Aricept 10mg HS, Zyprexa 5mg HS, Lantus 18U HS, Regular insulin 4U with each meal
HbA1c 6.9% Accucheck history: unavailable due to
resident refusal and combativeness during fingerstick
Osteoporosis
Fracture risk with increasing age
OP prevalence in middle age = 4% OP prevalence age >80 = 44-52% 80% of hip fractures occur in women > age 65
years, but incidence increases with age65-69 years: 21 fractures per 10,000 women
9 fractures per 10,000 men85-100 years: 325 fractures per 10,000 women
236 fractures per 10,000 men
O’Connell MB, Fritsch MA, 2010
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Consequences Following hip fracture
Only 40% of patient return to pre-fracture level of mobility
Long term care placement required in 20-75%
Mortality (higher in men, up to 38%)Health care costs $34,300 per event
12th highest Medicare hospital expenditure
2 million home health visits for post hospital fracture care annually
National Osteoporosis Foundation www.nof.org/prefessionals/Clinician_Guide
Data based on living environment Community:
Hip fracture risk increases by 50% for every 1 SD decline in BMD
OP prevalence increases from:OP prevalence in middle age = 4%OP prevalence age >80 = 44-52%
Long term care:Only 3% of residents have BMD within 1 SD of
adult normative BMDOP prevalence increases from
65-74 years: 63.5%>85 years: 85.8%
Zimmerman SI et al. 199
Data based on living environment Higher rate of fractures in long term care
environments as compared to community
Less represented in clinical trialsMore likely to have underlying cognitive,
functional, or renal impairment
Dementia is a significant risk factor for recurrent fracture
Less likely to be prescribed drug therapy
10-20% of residents with OP or h/o fracture will receive drug therapy
Crilly RG et al. JAGS 2010 Schneider DL. Curr Osteoporos Rep 2008, Mitani S et al. 2010, Colon-Emeric C et al. 2007
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http://www.shef.ac.uk/FRAX/
Post menopausal OP
Bone resorptionAssociated with estrogen loss during and
in the first few years after menopause resulting in increased osteoclast number and activity
Affects mostly trabecular bone →→vertebral fractures among women
Desired MOA of drug therapy includes suppression of osteoclast activity
Duque G, Troen BR. JAGS 2008
MOA of various OP treatmentsOsteoclast
Bisphosphonates ↓ differentiation and activity, ↑ apoptosis
Calcitonin ↓ activity, ↑ apoptosis
SERM ↓ differentiation and activity
Teriparatide ↑ activity
Denosumab ↓ differentiation and activity, ↑ apoptosis
Vitamin D ↑ activity
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OP associated with aging
Reduction of bone formationPartly associate with estrogen loss but
also with reduction number and differentiation of osteoblasts and a relative increase in bone marrow adipose
Affects mostly cortical bone →→ hip fractures in both men and women
Desired MOA of drug therapy would be suppression of osteoclasts, maintenance or regeneration of osteoblasts, and reduction in adipose formation
Duque G, Troen BR. JAGS 2008
MOA of various OP treatmentsOsteoclast Osteoblast Adipocyte
Bisphosphonates ↓ differentiation and activity, ↑ apoptosis
↑ differentiation and activity, ↓ apoptosis
Calcitonin ↓ activity, ↑ apoptosis
--
SERM ↓ differentiation and activity
--
Teriparatide ↑ activity ↑ differentiation, activity, and survival
↓ differentiation
Denosumab ↓ differentiation and activity, ↑ apoptosis
--
Vitamin D ↑ activity ↑ differentiation and activity, ↓ apoptosis
↓ differentiation
Fracture data by classVertebral Non-vertebral Age Gender
Bisphosphon-ates
High level of evidence
High level of evidence (agent specific)
Age-Independent
Male and Female (agent specific)
Calcitonin Moderate level of evidence
Low level of evidence
Insufficient data in advanced age
Predominantly female
SERM High level of evidence
Insufficient evidence
Favors younger
Female
Teriparatide High level of evidence
Moderate level of evidence
Age-Independent
Female and Male
Denosumab High level of evidence
High level of evidence
Insufficient data in advanced age
Female
Vitamin D Moderate level of evidence
Moderate level of evidence
Advanced age, institutionalized
Female
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Bisphosphonates
4 nitrogen containing bisphosphonates approved for osteoporosisAlendronateRisedronateIbandronateZoledronic acid
All have data demonstrating reduction in morphologic vertebral fractures for up to 3 years
Vertebral fracture, NNT
Drug Study Subject Age
Absolute risk ↓ (%)
NNT P value
Alendronate 5-10mg/day
FIT 55-81 7.0 15 <0.001
Risedronate 5mg/day
VERT-NA <85 5.0 20 0.003
Ibandronate2.5mg/day
BONE 55-80 4.9 21 <0.0001
Zoledronicacid 5mg/15min once yearly
HORIZON 65-89 7.6 14 <0.001
Ringe JD, Doherty JG. Rheumatol Int. 2010
Non-vertebral fractures, NNT
Drug Study Subject Age
Absolute risk ↓(%)
NNT P value
Alendronate 5-10mg/day
FIT 55-81 1.1 91 0.047
Risedronate 2.5-5mg/day
HIP 70-79 1.1 91 0.02
Zoledronicacid yearly
HORIZON 65-89 1.1 91 0.002
Ibandronate -- -- -- -- --
Ringe JD, Doherty JG. Rheumatol Int. 2010
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Differences in FDA approved indication
Post-menopausal OP
Glucocorticoid Induced OP
Men
Alendronate Yes Yes* Yes†
Risedronate Yes Yes* Yes*
Ibandronate Yes No No
Zoledronicacid
Yes Yes† Yes
*Fracture data †Bones density data
Long term data - Ibandronate
BONE – 3 years of treatment with 2.5mg/day in women with T score -2.0 or less and h/o 1-4 vertebral fractures62% reduction in vertebral
fracturesReduction in hip/non-vertebral
fractures was non-significant
Chestnut CH et al. J Bone Miner Res 2004
Long term data - Zoledronic acid HORIZON – 3 year initial treatment period
Subjects with BMD of -2.5 or less, or -1.5 with h/o vertebral fracture received yearly infusion of 5mg over 15 min
70% reduction vertebral fracture, 41% reduction hip fracture, 25% reduction in other non-vertebral fractures
Subgroup analysis of subjects with previous hip fracture 46% reduction in vertebral fracture, 27% reduction in
non-vertebral facture
Time to effect: vertebral fractures = 12 months, hip and non-vertebral fractures = 24 months
Mortality benefit: 28% reduction in death from any cause among treatment subjects
Black DM et al. N Engl J Med 2007
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Long-term data – Zoledronic acid
Anti-fracture data not reported beyond 3 years with 5mg yearly regimen
2mg and 4mg doses have been evaluated for 5 yearsSustained increases in BMD and
reductions in bone turnover
BMD gains achieved by month 36 maintained over next years
Devogalaer JP et al. Osteoporos Int. 2007
Long term data - Risedronate
VERT – 3 year initial treatment phaseVERT – North America:
All subjects had h/o vertebral fracture and received 5mg/day
41% reduction in new vertebral fracture, and 39% reduction in non-vertebral fracture
VERT – multinational49% reduction in new vertebral fractures,
non-significant recuction in non-vertebral fractures
Time to effect: 6 months
Harris ST et al. JAMA 1999, Reginster J et al. Osteoporos Int 2000
Long-term data - Risedronate
VERT Multinational extended 2 years
Initial 3-year fracture reduction was maintained over next 2 years: 59% reduction in vertebral fractures during years 4 and 5
After the 5 year study period, all patients offered risedronate therapy open-label for 2 more years
In subjects continuing therapy vertebral and non-vertebral fracture rates in years 6-7 were similar to those by year 3
Sorensen OH et al. Bone 2003, Mellstrom DD et al. Calcif Tissue Int 2004
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Long term data - Alendronate
FIT – 3 year initial treatment phaseAll subjects received 5mg/day for 2 years,
then 10mg/day thereafter47% reduction vertebral fractures, 51%
reduction hip fractures Fracture free patients continued to year 4
44% reduction vertebral fractures Time to effect: vertebral = 12 months, hip and
non-vertebral = 18-24 months
Black DM et al. Lancet 1996
Long-term data - Alendronate
FLEX – long term extension of FITAll patients treated for 5 years, followed
by additional 5 years of either alendronate 5-10mg/day or placebo
At 10 years, no difference in morphometric vertebral or non-vertebral fractures between treatment or placebo
However 55% reduction in clinically diagnosed vertebral fractures among patients who continued treatment
Black DM et al. JAMA 2006
Renal function
Bisphosphonates excreted unaltered through kidneys via filtration
Official recommendations:Avoidance use for CrCl <30ml/min
Based on lack of inclusion of subjects with >Stage 4 kidney disease in clinical trials
Data supporting use of alendronate and risedronate with CrCl <30ml/minUse still not recommended in Stage 5
kidney disease
Miller PD et al. J Bone Miner Res 2005, Miller PD et al. J Bone Miner Res 2008 and Jamal SA et al. J Bone Miner Res 2007
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Renal function - safety
No significant effect of alendronate or risedronate on markers of renal function after 12 months BUN, SCr, CrCl, calcium, phosphorus, or uric acid
No increase in vascular calcification among alendronate users with Stage 3 or 4 CKD after 18 months
Wise to differentiate OP from adynamic bone disease associated with renal osteodystrophy Check Vitamin D and PTH levels before initiating the
bisphosphonate?
Yanik B et al. 2007, Toussaint et al. 2010, Ammerling R et al. 2010
Atypical fractures?
Subtrochanteric fractureCase report / case series data with alendronate
Thought to be due to excessive reduction in bone remodeling
May be due more to osteoporosis itself than drug therapySubtrochanteric fractures represent <1% of all clinical
fractures and >90% occur in patients NOT taking bisphosphonate therapy
No increased incidence of non-vertebral fractures after 10 years of alendronate treatment in FLEX trial
Warnings in product information for alendronate required in Europe, and now recently, in U.S.No reports of subtrochanteric fracture or required
warnings with risedronate, ibandronate or zoledronic acid
Goh SK et al. 2007, Lenart et al. 2008, Kwek et al. 2008, Neviaser AS et al. 2008, Abrahamsen B et al. 2009, Boonen A et al. 2008, Pazianas et al. 2010
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More recent data
IOF working group report, 20111
Assuming ave. population risk of 1% per for hip fracture = 300 fx for every 10,000
Assuming 36% efficacy rate (RR=0.640), 108 hip fractures are averted (and 750 other fractures)2
Assuming > 5years treatmentSubtrochanteric fractures double, from 3 to 6
1. Rissoli et al. Osteoporos Int 2011, 2. Kanis et al. Bone 2005
Other concerns with long term use?
GI toxicities Well described – administration requirements must be explicitly
adhered to
Bone/joint/muscle pain Case report literature Not reported in FIT, VERT, or BONE, but more common with
treatment in HORIZON
A-fib (specifically A-fib events characterized as serious) Reported in HORIZON, but data conflicting with oral therapy
Ocular inflammation Scattered reports, existing uveitis a precaution for use
ONJ Incidence may be < 1 in 100,000 patient-years of exposure
Pazianas et al. Therapeutics and Clin Risk Manag 2010
Dilemmas based on available data
Mechanisms of bone loss differ between Post-menopausal OP and OP of aging
Treatment options are limited to agents that can influence the underlying pathophysiology
BMD losses and fracture risk increase with age, not all cohorts equally represented in clinical trials
Age 80-81 is top enrolled age for most studies, some data to age 85 or 89
Long term care populations under-studied, under-diagnosed, and under-treated
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Dilemmas based on available data
Hip fracture benefit not equal among agents or among subject cohortsOnly Alendronate, Risedronate and Zoledronic acid
Many patients initiating drug therapy are likely to live with OP longer than the durations of treatment evaluated
Elderly patients at high fracture risk are often likely to have renal insufficiency, but lack of inclusion of such patients in clinical trials
Long term side effects controversial but are still concerns that need to be dealt with
Drug holiday?
Discontinuation of bisphosphonate therapy Monitoring changes in BMD and markers
of bone turnoverDuration of therapy before discontinuation
and duration of drug holiday depend upon agentDuration of existing efficacy dataDegree and duration of reduction in
markers of bone turnover / “Reversibility” of effects
Reports of post-D/C fracture rates
Reductions in bone turnover
Bisphosphonates with high mineral binding affinity and potential retention
AlendronateZoledronic acid
Bisphosphonates with lower mineral binding affinity and retention
Higher “reversibility”
Risedronate
Non-nitrogen containing bisphosphonates (e.g. etidronate)
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Post D/C data - Alendronate
Following 5 years of therapy, biomarkers in the placebo increased gradually over 5 years10 year biomarkers were not significantly different
between 5 and 10 year treated subjects
Remained below premenopausal levels for up to 5 years post discontinuation
No differences in all morphometric or non-vertebral fractures between groups, but a significant reduction in clinically diagnosed vertebral fractures
Black DM et al. JAMA 2006
Post D/C data - Zoledronic acid
Suppression of bone turnover evaluated after single infusion:
Close to maximal achieved suppressionSuppression sustained for at least 1
year
Year extension vs. placebo52% reduction in morphometric
vertebral fracture vs placebo (fracture rate 3.0 vs 6.2%)
Black et al. J Bone Miner Res 2012
Post D/C data - Risedronate VERT – North America
Patients discontinued therapy after 3 years, but subjects were monitored for an additional yearMarkers of bone turnover returned to
pretreatment levels within 1 year after discontinuation
HOWEVER, BMD decreased but remained higher than baseline or placebo BMD, AND
Rate of new vertebral factures was still 46% lower among the former risedronate treated subjects
Watts NB, Osteoporos Int 2008
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Recommendations for mild-moderate fracture risk
Bisphosphonate therapy for 3-5 years
Possible drug holiday* (grade B)Continue drug holiday until significant loss of
BMD or until recurrent fracture
Use of markers of increased bone turnover may also provide guidance regarding duration of drug holiday (grade C)
*Recs specific to alendronate, risedronate, zoledronic acid. Recs NOT specific to med or individuals taking glucocorticoids
Watts NB, Diab DL. J Clin Endocrinol Metab. 2010
Recommendations for moderate - high fracture risk Bisphosphonate therapy for 5-10 years* Possible drug holiday for 1-2 years, or until
significant loss of BMD or new fractureOptimize vitamin D supplementation
during therapy and holidayAlternative osteoporosis treatment may be
indicated during bisphosphonate drug holiday
*Rec specific to alendronate. Recs NOT specific to med or individuals taking glucocorticoids
Watts NB, Diab DL. J Clin Endocrinol Metab. 2010
Summary Points
Patients live with OP longer than treatment durations studied
Pathophysiology of OP changes with age Bisphosphonates offer beneficial mechanism of action
Fracture risk increases with age Maximum age in most clinical trials is 85 years
Efficacy of drug therapy demonstrated within 2 years Older patients who are ambulatory and have life
expectancy of at least this long are potential candidates for therapy
Safety profile of bisphosphonates present some concern, but fractures also carry significant consequences Drug holidays may provide a mechanism to balance safety
and efficacy over long term
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Sample Patient
60 year old community dwelling female patient
PMH: Osteoporosis with history of vertebral fracture
DEXA -2.7 spine
Sample Patient
86 year old community dwelling female patient
PMH: Osteoporosis with history of hipfracture
DEXA: -2.7 spine, -2.5 hip
Sample Patient
86 year old female patient in Assisted Living center
PMH: Osteoporosis with history of hipfracture, Mild cognitive impairment
DEXA: -2.7 spine, -2.5 hip
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Sample Patient
86 year old community dwelling malepatient
PMH: Osteoporosis with history of hipfracture
DEXA: -2.7 spine, -2.5 hip
Sample Patient
86 year old institutionalized female patient PMH: Osteoporosis with history of hipfracture, Mild cognitive impairment, declining renal function
DEXA: -2.7 spine, -2.5 hip CrCl: 29ml/min
Vitamin D level: 19
(What if we added a swallowing problem?)