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1/22/2014

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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


4736 72 650

Systolic HTN in Europe (SYST-Eur)Lancet 1997;350:757-64

4695 70 441


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


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


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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)


170/77 143/68

Systolic HTN in Europe

(SYST-Eur)Lancet 1997;350:757-64

174/86 151/79


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


PMH: TIA (on aspirin therapy), declining renal function, and Type 2 diabetes


CrCl: 35 ml/min

Sample Patient

86 year old institutionalized male patient

PMH: Alzheimer’s disease, declining renal function


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


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


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


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


PMH: Heart Failure with preserved LVEF Current medications: Lisinopril 20mg BID,

furosemide 20mg daily, KCL 10mEq daily, aspirin 31mg daily


Sample 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


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


PMH: TIA (on aspirin therapy), declining renal function and Type 2 Diabetes


CrCl: 45 ml/min HbA1c: 8.8%

Fasting BG: 130-158 Postprandial BG: 180-302

Sample Patient


PMH: TIA (on aspirin therapy), declining renal function, Type 2 diabetes

Current medications: glyburide 5mg BID


CrCl: 35 ml/min

HbA1c: 8.8%

Fasting BG: 130-158

Postprandial BG: 180-302

Provider wants to add insulin

Sample 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


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


PMH: Osteoporosis with history of vertebral fracture

DEXA -2.7 spine

Sample 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


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Sample Patient

86 year old community dwelling malepatient

PMH: Osteoporosis with history of hipfracture


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?)

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