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MEDICATION SAFETY

Editors: Michael Woodward,Director, Aged and Residential Care Research, Mary Britton,Consultant Geriatrician,

Rohan Elliott,Clinical Pharmacist, Graeme Vernon,Senior Drug Information Pharmacist, Austin Health; and Robyn

Saunders,Consultant Pharmacist, Victoria.

GERIATRIC THERAPEUTICS

Cardiovascular Risk Reduction in the Extreme ElderlySeema Parikh, Kerith Sharkey, Barbara Workman

Seema Parikh, MBBS, FRACP, MPH, Academic Geriatrician, Monash Ageing

Research Centre, School of Public Health and Preventive Medicine, Monash

University; Consultant Geriatrician, Caulfield General Medical Centre; Senior

Lecturer, Faculty of Medicine, Nursing and Health Sciences, Monash University,

Kerith Sharkey,BA, BSc (Hons), MSocHlth (Eth), Manager, Monash Ageing

Research Centre, School of Public Health and Preventive Medicine, Monash

University, Barbara Workman,MBBS, FRACP, MD, AFRACMA, Medical

Director, Rehabilitation and Aged Services, Monash Health; Director, Monash

Ageing Research Centre, School of Public Health and Preventive Medicine,

Monash University; Professor of Geriatric Medicine, Faculty of Medicine,

Nursing and Health Sciences, Monash University, Clayton, VictoriaCorresponding author:Dr Seema Parikh, Monash Ageing Research Centre,

Kingston Centre, Cheltenham Vic. 3192, Australia.

E-mail: [email protected]

ABSTRACT

An American Heart Association statement on secondary

prevention of coronary heart disease in the elderly reported

that 50% of women and 70% to 80% of men over 75 years

have obstructive coronary artery disease. The total direct and

indirect costs of cardiovascular disease and stroke in the US for

2007 was around $286 billion and annual costs are projected

to rise to over $1 trillion by 2030. Significant emphasis is

now placed on prevention and risk factor modification of

cardiovascular disease. The proportion of the populationaged 85 years and older (the extreme elderly) is projected to

increase to 151% by 2030. This review focuses on reducing

risk in coronary heart disease and congestive heart failure in

the extreme elderly. We review modifiable cardiovascular risk

factors (hypertension, lipid profile, lifestyle modification),

pharmacological strategies (statins, beta-blockers,

angiotensin converting enzyme inhibitors, angiotensin II

receptor blockers, aspirin) and the available evidence for

their use in extreme old age. There is insufficient evidence to

reach major conclusions with respect to cardiovascular risk

reduction in the extreme elderly. Further trials involving older

patients are needed before evidence-based recommendations

can be formulated for this population.

J Pharm Pract Res 2013; 43: 62-8.

INTRODUCTION

During 2007-08, around 3.5 million Australians hadcardiovascular disease (CVD), which was responsible for34% of all deaths.1CVD was the most expensive chronicdisease in Australia, costing $5.9 billion in 2004-05.1An American Heart Association statement on secondaryprevention of coronary heart disease in the elderly reportedthat 50% of women and 70% to 80% of men over 75 yearshave obstructive coronary artery disease.2The total directand indirect costs of CVD and stroke in the US for 2007was around $286 billion and annual costs are projected

to rise to over $1 trillion by 2030.3

Significant emphasisis now placed on prevention and risk factor modificationof CVD.

The impact of CVD is greatest in the older personwhere hospitalisation and death rates are usually the

highest.1 CVD may be defined as all diseases andconditions of the heart and blood vessels. Although theseinclude coronary heart disease, stroke, congestive heartfailure (CHF), cardiomyopathy, hypertension, peripheralvascular disease and rheumatic heart disease, this reviewfocuses on reducing risk in coronary heart disease andCHF in the extreme elderly.

Age is an independent risk factor for CVD and ageingis associated with an increasing prevalence of coronary

artery disease, heart failure and cerebrovascular disease.The prevalence of CVD in Australia for those over 75years is estimated to be 62%, and coronary heart diseaseis estimated to be present in 15% of females aged 75 to84 years and 22% of females over 85 years with a higherprevalence in males: 23% and 28% respectively.1Althoughthe prevalence of CHF is decreasing due to improvementsin the treatment of hypertension and CVD, it remains amajor morbidity for older people.4

Traditionally, the elderly have been defined as thoseaged 65 years and older, which is reflected in multipledomains of society, policy and economics. In healthcare

literature, references to the elderly can range from those

aged 60 years up to 100 years. The significant heterogeneity

in function, cognition and medical complexity across

this age range may not be apparent. With ageing, there

is higher prevalence of functional decline, sensory

impairment, frailty, cognitive impairment and multi-

morbidity that can define the young old (< 85 years) and

the old old ( 85 years) as two distinct populations. The

proportion of the population aged 85 years and older (the

extreme elderly) is projected to increase to 151% by

2030.5Given the contemporary focus on evidence-based

medicine to guide clinical decision making, it is essential

to evaluate the available literature in adults 85 years and

older, as clinicians will be increasingly challenged to

make therapeutic decisions in this population.

Risk reduction in CVD includes nutritional,interventional and pharmaceutical domains. While

strategies such as revascularisation and glycaemic control

in diabetics are important for reducing risk, they are

beyond the scope of this review. We review modifiable

cardiovascular risk factors, pharmacological strategies

and the available evidence for their use in extreme old age.

MODIFIABLE RISK FACTORS

Hypertension

The prevalence of hypertension is reported to be 74%

in people aged 80 years and older.6There is evidence of

benefits from lowering blood pressure in middle-aged and

elderly people.7A meta-analysis reported systolic blood

pressure reduction to between 140 and 150 mmHg had

mortality and morbidity benefits for people aged 75 years

and older.8However, very low blood pressure is associated

with mortality in the elderly. Observational data from a

62 Journal of Pharmacy Practice and Research Volume 43, No. 1, 2013.


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Journal of Pharmacy Practice and Research Volume 43, No. 1, 2013. 63

cohort of 331 hospitalised subjects aged 70+ years (mean

85 7) support a j-shaped curve relationship with low

diastolic blood pressure ( 60 mmHg) associated with

increased all-cause death and cardiovascular death. The

study also found an inverse linear relationship between

systolic blood pressure and cardiovascular mortality.9

While many studies focus on outcomes for control

of hypertension in those aged 60+ years, few examine

outcomes in extreme old age. The randomised controlled

Hypertension in the Very Elderly Trial (HYVET) included

3845 patients from three continents, aged 80 to 105 years,

with sustained systolic blood pressure of 160 mmHg

or more. Indapamide or a matching placebo was given

to reduce blood pressure and perindopril or a matching

placebo was added if necessary to achieve the target blood

pressure of 150 mmHg. The primary endpoint was fatal or

non-fatal stroke. After a median follow-up of 1.8 years the

study was prematurely terminated because ongoing use

of placebo was noted to be dangerous. Active treatment

was associated with a 30% reduction in fatal or non-fatal

stroke and in decompensated heart failure. The benefits of

treatment became apparent within the first year.10

A meta-analysis which included the HYVET and

pilot HYVET data evaluated antihypertensive therapy

compared with placebo in patients aged 80 years and older

with the primary outcome of total mortality. This analysis,

which included 6701 patients from eight trials concluded

antihypertensive therapy significantly reduced the risk

of stroke (35%), cardiovascular events (27%) and heart

failure (50%); there was no effect on total mortality.11

The Blood Pressure Lowering Treatment Trialists

Collaboration examined 31 trials with over 190 000

participants and compared patients below 65 years (n =

96 466) with those 65 years and older (n = 94 140). They

concluded there were no significant differences in major

cardiovascular outcomes and the benefits of angiotensin

converting enzyme (ACE) inhibitors, calcium channel

blockers, diuretics or beta-blockers to lower blood pressure

are largely comparable across the age groups.12However,

they acknowledged the relative paucity of data for those

aged over 80 years and less than 50 years.12A previous

non-age specific meta-analysis by the Blood Pressure

Lowering Treatment Trialists Collaboration confirmed

treatment with any commonly-used regimen reduces the

risk of total major cardiovascular events, and that larger

reductions in blood pressure produce larger reductions in

risk.13

Draft guidelines for hypertension from the National

Institute of Clinical Excellence recommend a target clinicblood pressure below 150/90 mmHg in people aged 80+

years with treated hypertension, incorporating data from

HYVET.14However, treatment may be limited by postural

hypotension, falls, postprandial hypotension, electrolyte

disturbances and renal impairmentoutweighing the

benefits of aggressive hypertension control.

Lipid Profile

Current Australian Pharmaceutical Benefits Scheme

guidelines regarding eligibility for lipid lowering

treatment include a total cholesterol level of greater

than 5.5 mmol/L to less than 9 mmol/L, depending on

concurrent risk factors and subgroup populations.15 It is

unclear whether hypercholesterolaemia is a cardiovascularrisk factor in extreme old age. A review of observational

studies on cholesterol and mortality in the 80+ age group

demonstrated a trend where all-cause mortality was

highest when total cholesterol was lowest. The authors

concluded that low total cholesterol level (< 5.5 mmol/L)

was associated with the highest mortality rate in people

aged 80 years and older.16With regard to CVD-specific

mortality among those 80 years and older, results varied

from finding total cholesterol associated positively and

negatively, or not at all. Similarly, the association between

high-density lipoprotein, low-density lipoprotein and total

mortality was inconclusive in observational studies.16

Interpretation of these studies is difficult and lipid profiles

may need to be viewed in the context of nutritional state,

clinical examination and comorbidities.

Lifestyle Modification

Lifestyle modifications to reduce risk of CVD include

dietary changes, exercise and smoking cessation. Lifestyle

behavioural modifications for mid-life adults have been

recommended and aggressively marketed, but there is

little reference to the extreme elderly due to lack of data.

Dietary ChangesDespite limited evidence for dietary changes in the 80+ age

group, recommendations can be made for consumption of

low levels of saturated fat, low salt intake (in the presence

of hypertension and/or CHF) and weight loss to aim

for a body mass index less than 30.7 Centenarians are

considered the best example of successful cardiovascular

ageing, with a lower incidence of CVD.17Several reports

have documented that centenarians have followed a

series of good habits initiated at a young age. Caloric

restriction, moderate intake of alcohol and abundant intake

of vegetables rich in antioxidants correlate positively with

longevity in genetically predisposed individuals.18

Exercise

The relationship between exercise and cardiovascular risk

reduction has not been well studied in the extreme elderly.

The level of exercise is often limited by musculoskeletal

comorbidities, cognitive issues and concurrent cardio-

respiratory disease. There are benefits of exercise with

regard to fall prevention, osteoporosis and quality of life,

regardless of the direct relationship to CVD.19,20

Smoking Cessation

Almost 10% of adults aged 65+ years are smokers and

50% of smokers will die from tobacco-related illness.21

The benefits of smoking cessation in CVD are almost

immediate, with significant improvements in bloodpressure and heart rate within 24 hours of cessation.

Within 1 year of abstinence, the risk of cardiovascular

events such as myocardial infarction (MI) and stroke

reduce by half (compared with continued smoking).22Risk

reduction of MI post smoking cessation applies to younger

(25 to 49 years) and older (50 to 64 years) populations. 23

There are few studies on smoking cessation rates in old

age (particularly in those 70+ years).24

Smoking cessation strategies include behavioural

approaches and pharmacotherapy. No clinical trials

focusing on smoking cessation strategies or outcomes in

the elderly are available. Nicotine replacement therapy

(NRT) is the most widely used form of pharmacotherapy

and includes transdermal patches, nasal spray, gum,lozenges and nicotine inhalers.25 NRT was found to be

effective when compared with placebo; these studies

excluded participants 65+ years.


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Some psychotherapeutic drugs, such as bupropion,

clonidine and nortriptyline have also been studied; age

range of patients included in these trials was 18 to 70

years. Smoking cessation rates at 1 year were better with

varenicline (a nicotinic acetylcholine receptor partial

agonist) (23%) than bupropion (15%) or placebo (10%);

age range examined was 18 to 75 years. The US Food

and Drug Administration has advised that varenicline

may be associated with a small increased risk of certain

cardiovascular events in patients who have cardiovascular

disease after a trial involving 700 people with CVD was

completed. While these events did not reach statistical

significance, they invite further investigation.26Althoughthere is little direct evidence for individual strategies inpatients aged 85 years and older, the benefits of smokingcessation are clear up to the age of 75 years.

PHARMACOLOGY

Statins

The role of statins in lowering lipids has been wellestablished. However, their role in cardiovascular risk

reduction independent of their effect on cholesterolthrough improving endothelial function is of recentinterest.27 Multiple randomised controlled trials haveconfirmed the benefit of statins in middle-aged adultsincluding cholesterol reduction and secondary preventionof further cardiovascular events.

A few studies examining cardiovascular risk haveincluded participants aged 80+ years.16 The randomisedcontrolled PROSpective study of Pravastatin in Elderlyindividuals at Risk (PROSPER) examined the benefit ofpravastatin in an elderly cohort of men and women with ahigh risk of developing CVD and stroke. Participants wereaged 70 to 82 years and were followed for 3.2 years witha primary endpoint which was a composite of coronary

death, non-fatal MI and fatal or non-fatal stroke. Theauthors concluded that pravastatin for 3 years reducedcoronary heart disease in the elderly. The primary endpointwas reduced by 23% in men but only 4% in women.28Thetrial did not include patients of extreme old age, so thereremains a gap in the evidence for this age group.

Another randomised controlled trial studiedrosuvastatin in older patients with systolic heart failureof ischaemic cause examining the primary compositeoutcome of death from cardiovascular causes, non-fatalMI or non-fatal stroke. Over 41% of the 5011 participantswere aged 75+ years. A subgroup analysis examinedpatients aged 77+ years. The primary outcome was not

significantly different between the two groups but therewas a reduction in cardiac hospitalisations in the grouptreated with rosuvastatin.29

No prospective trials have examined statin efficacyin adults of extreme age exclusively. A recent Cochranereview examining statins in primary prevention of CVDreported reductions in all-cause mortality, major vascularevents and revascularisations in people without evidenceof cardiac disease.30However, age-specific analyses wereabandoned due to lack of adequate data. A meta-analysisof nine trials encompassing 19 569 patients with anage range of 65 to 82 years with coronary heart diseasereported a reduction in mortality, non-fatal MI, need forrevascularisation and stroke.31 An observational cohort

study of 14 907 post-MI patients aged 80 years and olderreported lower cardiovascular mortality in those receivingstatins at discharge.32

There is insufficient primary evidence to recommendinitiating or continuing statins in those aged 85 years andolder.30No clinical trials have been designed to addressprimary and secondary prevention of coronary events inthe extreme elderly using statins.33

Beta-Blockers

Beta-blockers are used in acute coronary syndromes,

hypertension, stable angina and CHF. The role of beta-blockers in CHF will be discussed given prevalencerises sharply with age (over 10% in those aged 80 yearsand older).34The median age of presentation of CHF is75 years.34 Concerns regarding tolerability and relativeefficacy of beta-blockers in extreme old age havebeen raised due to comorbidities, frailty and decliningfunctional abilities.35 Several useful properties of beta-blockers may account for their beneficial role in CHF:reduce adrenergic drive, improve autonomic balanceand reduce heart wall stress.36A systematic review of 22randomised controlled trials reported that beta-blockersreduced hospital admissions and risk of death in patients

with a low ejection fraction.37

While the mean age of thepredominantly male population was 61 years, it providessome evidence supporting the use of beta-blockers inolder people.37

The Study of the Effects of Nebivolol in Outcomesand Rehospitalization in Seniors with Heart Failure(SENIORS) evaluated a beta-blocker in patients aged 70years and older (n = 2128) regardless of ejection fraction;mean age of participants was 76 years (range 6995).38Theprimary outcome was a composite of all-cause mortalityor cardiovascular hospital admission (time to first event).The proportion of patients who suffered the primaryoutcome in the nebivolol group was 31% compared with35% in the placebo group (HR 0.9; 95%CI 0.71.0) a

statistically significant difference. A subgroup analysisdid not reveal significant differences for patients aged 75+years. Nebivolol was well tolerated in all age groups.

Two major trials reported the benefit of carvedilol inheart failure. The randomised controlled Carvedilol orMetoprolol European Trial (COMET) compared carvedilolwith metoprolol; the mean age of the study populationwas 62 years.39Some data were presented for participantsunder 65 years and over 65 years; no conclusion can bereached for the extreme elderly. Similarly, the randomised,double-blind, placebo-controlled Carvedilol ProspectiveRandomized Cumulative Survival Study Group(COPERNICUS) trial investigated carvedilol in addition

to standard heart failure treatment in 2289 patients withmoderate to severe heart failure with an ejection fractionless than 25%; mean age of participants was 63 years.40Subgroup analyses were presented for several parameters,such as age. The reduction in mortality and combined riskof death or hospitalisation favoured cardvedilol. However,the elderly subgroups identified were aged 65+ years andthe size of the benefit appeared to be quantitatively smallerin this age group. Therefore, applying these results to thoseof extreme age may be difficult. Retrospective analyses ofthe Metoprolol CR/XL Randomized Intervention trial inHeart Failure (MERIT-HF) of elderly patients aged 65+years examined efficacy, safety and tolerability. Althoughpatients aged 75+ years were studied, the oldest patients

were 80 years of age.41This analysis reported metoprololCR/XL was easily instituted, safe and well tolerated wheninitiating therapy and long-term follow-up in the elderlywith systolic heart failure.41


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There is weak evidence of benefit for using beta-

blockers in CHF in the extreme elderly. These should be used

cautiously to ensure tolerability. Careful patient selection

and close monitoring are essential to minimise risks. In

the Cardiovascular Health Study, 18% of community-

dwelling older adults had orthostatic hypotension.42

The American College of Cardiology and the American

Heart Association guidelines recommend beta-blockers

in all chronic systolic heart failure patients unless there

is a history of intolerance or a contraindication.43 Beta-

blockers should be commenced at low doses and titrated

accordingly.43 The impact on heart rate, blood pressure

and symptomatic dizziness need attention in relation

to functional status. Concurrent medications must be

considered in the decision to prescribe beta-blockers. For

example, those on small doses of ACE inhibitors may

tolerate beta-blockers well.44

Data for beta blockade in those aged 80 years and older

post-MI are limited. The Cardiovascular Co-operative

Project reviewed over 200 000 records and reported that

mortality was 32% lower in patients aged 80 years and

older who received beta blockade post-MI.45

Prospectivetrial data in this age group are not available.

Angiotensin Converting Enzyme Inhibition

ACE inhibitors and angiotensin II receptor blockers

(ARBs) have been studied in heart failure, ischaemic

heart disease and stroke. However, only a few trials have

included patients of extreme old age. Table 1 displays

major clinical trials which included older participants.

Of note, GISSI-3 had 27% of subjects over 70 years of

age.46 The absolute reduction for a combined mortality

and cardiovascular endpoint in the elderly participantswas 3.5%. The non-age specific mortality reduction for

the other trials was 4% to 6%. EUROPA, ISIS-4, Val-Heft

and OPTIMAAL presented subgroup analyses of patients

65 years and older with similar results to the younger

counterparts.47-50 A post hoc analysis from the HOPE

study was later published evaluating 2755 patients aged

70 years and older.51Those assigned to ramipril had fewer

major vascular events compared to placebo. Furthermore,

ramipril was safe and well tolerated.34

A meta-analysis of 32 randomised clinical trials has

demonstrated the effectiveness of ACE inhibitors for

reducing morbidity and mortality in heart failure. The

benefits are similar for patients over 80 years and 60years and younger.52A retrospective cohort study of frail

elderly patients (mean age 85 years) reported that patients

Table 1. Trials of angiotensin converting enzyme inhibition that included older people

Study Drug Population

Patients 85

years Primary outcome Results

CONSENSUS Enalapril vs placebo CHF NYHA IV Yes All-cause mortality Significant decrease in

mortality at 6 and 12 months

GISSI-3 Lisinopril vs placebo Post-MI and CHF Yes All-cause mortality

LV dysfunction

Decrease in 6-week

mortality; decreased rate of

composite endpoint of death

and late-onset heart failure

ISIS-4 Captopril vs placebo Post-MI and CHF All-cause mortality Significant reduction in

mortality at 5 weeks

HOPE Ramipril vs placebo CV disease or diabetes

and/or one other CV risk

factor

Yes, n = 9297 Composite endpoint

of MI, stroke or CV

death

Decreased mortality, MI,

stroke in broad age range

PROGRESS Perindopril

indapamide vs

placebo

Prior stroke or TIA

within 5 years

Yes Stroke Decreased risk of recurrent

stroke

ALLHAT Lisinopril vs

chlorthalidone vs

amlodipine

Hypertension and one

CV risk factor

Yes, > 100

years

Combined fatal CHD

or non-fatal MI

No significant decrease in

primary outcome

EUROPA Perindopril vs

placebo

CHD Yes, up to 90

years

Composite endpoint

of CV death, MI or

cardiac arrest

Treatment group had fewer

CV events

PEACE Trandolapril vsplacebo

Stable CAD and normalor mildly reduced LV

function

Unclear, n =912 75 years

Death CV causes,MI/cardiac

revascularisation

No significant decrease inprimary outcome

Val-Heft Valsartan vs placebo CHF NYHA II-IV Yes Mortality or

combined mortality

and morbidity

Decreased morbidity and

mortality; beneficial effect

seen in those aged > 65 years

OPTIMAAL Losartan vs captopril Acute MI and CHF Yes All-cause mortality Non-significant difference in

total mortality

VALIANT Valsartan vs captopril

vs both

Acute MI and CHF Yes All-cause mortality Main outcome did not differ

between treatment groups

SCOPE Candesartan vs

placebo

Hypertension Yes, 70-89

years, 80

(21%) years

Composite endpoint

of CV death, non-

fatal stroke/MI

Slightly more effective

blood pressure reduction

with candesartan

VALUE Valsartan vs

amlodipine

Hypertension and CV

risk

Yes Cardiac event No difference in endpoint

CAD = coronary artery disease. CHD = coronary heart disease. CHF = congestive heart failure. CV = cardiovascular. LV = left ventricular.

MI = myocardial infarction. NHYA = New York Heart Association. TIA = transient ischaemic attack.



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receiving ACE inhibitors had 10% reduction in mortality

and a lower rate of functional decline. Data suggested

survival and functional benefits of ACE inhibitor therapy

in CHF pertains to patients aged s85 years and older.53

A systematic review reported the comparative

effectiveness of ACE inhibitors or ARBs for ischaemic

heart disease.54After examining 41 randomised controlled

trials, the authors concluded: adding an ACE inhibitor to

standard medical therapy improves outcomes, including

reduced risk for mortality and MI, in some patients with

stable IHD and preserved ventricular failure. Less evidence

supports a benefit of ARB therapy, and combination

therapy seems no better than ACE inhibitor therapy alone

and increases harms.54The analysis was not age specific.

Although ACE inhibition is an important element

of cardiac risk reduction, it needs to be balanced

with potential adverse reactions, such as orthostatic

hypotension, falls and renal impairment. Alternatively,

a retrospective review of 295 hospitalised older patients

reported significant survival benefit for those on ACE

inhibitors with perceived contraindications, such as

hypotension, renal insufficiency or severe aortic stenosis.44

Although the study was retrospective and had a small

study population, it illustrates benefits at older age. Patient

function, cognition and other domains must be considered

when prescribing; adopting a conservative approach to

dosing while actively titrating.

Aspirin

Primary Prevention

A meta-analysis of randomised controlled trials examining

the effect of aspirin on vascular and non-vascular outcomes

reported that aspirin reduced cardiovascular events by 10%

primarily by reducing non-fatal MI in primary prevention.

In contrast, there was a 70% excess risk of total bleeding

events (OR 1.7; 95%CI 1.22.5) and a higher than 30%

excess risk of non-trivial bleeding events (OR 1.3; 95%CI

1.11.5) in people receiving aspirin; mean age was 57

years (SD 4.1). A non-significant increase in the risk of

haemorrhagic stroke of about one-third was observed in

this meta-analysis.55

There are some data for patients aged 70+ years,

suggesting benefits outweigh the risks, but the data

are less clear than in younger age groups.56 Of nine

randomised controlled trials evaluating aspirin in primary

prevention of cardiovascular events, eight trials included

patients aged 70+ years. Results of subgroup analyses for

older participants were reported in six of these trials.57The

Physicians Health Study reported significant reduction inMI in these age groups; the Primary Prevention Project

showed a non-significant increase in coronary deaths for

the older age group; while the Womens Health Study

reported reduced risk of ischaemic stroke and MI for those

aged 65+ years. The role of aspirin in primary prevention

remains to be established.57-60

A primary prevention randomised, double-blind,

placebo-controlled trial, ASPirin in Reducing Events

in the Elderly (ASPREE) is in progress, assessing the

effect of enteric-coated aspirin 100 mg daily on duration

of disability-free survival in healthy participants aged

70 years and older. The study will recruit over 19 000

participants in Australia and the USA.61

Secondary Prevention

The efficacy of aspirin in occlusive CVD has long been

established in a number of populations through its anti-

platelet properties.62However, at high doses aspirin has

been postulated to have other biological mechanisms that

may decrease the risks of CVD, such as reducing elevated

levels of inflammatory markers, e.g. pro-inflammatory

cytokines, C-reactive proteins. The use of aspirin in

extreme old age has not been well studied. In older patients

(including 85 years) with established CVD, such as

coronary artery disease and cerebrovascular disease,

low-dose aspirin reduced the risk of further vascular

events, non-fatal stroke, non-fatal MI and vascular

death.63,64 However, concern about gastrointestinal

tolerability, especially bleeding, exists due to concurrent

multi-morbidity. Greater vigilance and consideration of

comorbidities, as well as cognitive and functional status

may be required.

DISCUSSION

The paucity of published cardiology trials which include

patients of extreme old age has been reported previously.Gurwitz et al.65 searched the literature (January 1966 to

September 1991) to identify drug trials in acute MI and

of the 214 trials, more than 60% excluded patients over

75 years. The bulk of literature in the elderly continues

to report on those aged 65 years and older, however

subgroup analyses are being presented more frequently,

as increasing lifespan is acknowledged. Some evidence is

available for the extreme elderly in cardiac risk reduction

but the evidence base is sparse when compared to all

available literature.

There are difficulties conducting clinical research

in the extreme elderly. Patient recruitment remains a

challenge as comorbidities limit their inclusion in trials.

Clinical drug trials often involve numerous visits to

hospital for investigations, which can impact on an older

persons ability to comply with study requirements.66

Issues of cognitive impairment and capacity to consent

can also present ethical dilemmas. There are implications

for resource allocation and preventive medical services

if we do not know the effect of interventions in the

extreme elderly, especially in the context of an ageing

population. Trials must attempt to enrol participants more

representative of older populations.

Goals of care of the extreme elderly must also be

considered on an individual basis. At this extreme end

of the age spectrum, patients wishes and life satisfaction

need to be acknowledged. Interventions that have animmediate effect on wellbeing may be more important

than preventing future illness. A longitudinal population

study of individuals aged 78 to 98 years found diagnoses,

such as stroke, dementia and cardiac disease were not

related to life satisfaction. Alternatively, depressive mood

and number of symptoms were significant predictors of

poor life satisfaction at 3 years.67

Underutilisation of preventive and treatment measures

addressing chronic disease has been documented in older

populations.68 Clinicians may be reluctant to initiate

medications because of the risks of polypharmacy

and increasing the risk of falls, cognitive decline and

various geriatric syndromes.69Medication adherence also

needs to be considered when prescribing and patient-friendly dosing regimens formulated. Clinicians need

to incorporate a comprehensive assessment of function,

cognition, comorbidities and goals of care into decision

making for cardiac prevention.



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In conclusion, there is insufficient evidence to reach

major conclusions with respect to cardiac risk reduction in

the extreme elderly. Further trials involving older patients

are needed before evidence-based recommendations can

be formulated for this population.

Competing interests:None declared

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Received: 20 April 2012

Revisions requested after external review: 5 February 2013

Revised version received: 19 March 2013

Accepted: 25 March 2013

Grant Value Closing date

Auditmaker Clinical Audit Grant $5000 31 August 2013

Hospira Pharmacist Award $10 000 31 July 2013

Roche Research Grant on

Quality and Safety

$10 000 31 August 2013

Celgene Pharmacy Grant $20 000 30 September2013

Grant schedule for 2013

SHPA Research and Development GrantsProgram

In 2013 the RDGAC transitioned to Queensland and willbe in the capable hands of a group of experienced clinicalpractitioners and researchers. Many thanks to the South

Australian team for their time and expertise in leading asuccessful RDGAC over the past 5 years. We congratulateAnna McClure, Joy Gailer, Sepehr Shakib, Manya Angley,Greg Roberts, Luke Grzeskowiak, Helen Lovitt and DellaAbsalom for their achievements.

The new committee includes: Tony Hall SHPA Federal Councillor and Lecturer,

Griffith University Dr Jason Roberts SHPA Fellow and Consultant

Pharmacist, Royal Brisbane and Womens Hospital Arna Neilson SHPA Queensland State Branch

representative Dr Neil Cottrell SHPA Fellow and Senior lecturer,

University of Queensland Jo Sturtevant Consultant Pharmacist, Princess

Alexandra Hospital Dr Peter Donovan Clinical Pharmacologist, Royal

Brisbane and Womens Hospital Dr Michael Barras (Chair) Assistant Director of

Pharmacy, Royal Brisbane and Womens Hospital Della Absalom Assistant to Federal Secretariat,

SHPAThe committee is privileged to retain Joy Gailer to

help guide the transition.The first two SHPA grants for the year have closed and

we thank all applicants. The remaining grants for 2013 arelisted, along with the respective closing dates. This year, to

compliment the Hospira Pharmacy Award and the RocheSafety and Quality Grant, will see the re-introduction ofthe Auditmaker Clinical Audit Research Grant. This grantis aimed at a researcher with aspirations to undertake aclinical audit using the Auditmaker software. The softwareis designed to assist with multi-centre data collection andanalysis; therefore we recommend applying for fundsto support a multi-site, collaborative project. The othermajor grant is the Celgene Pharmacy Grant to supportinformation technology in hospital pharmacy. This grantwas not awarded in 2012 and therefore $20 000 is nowavailable.

We encourage all pharmacists and technicians to

consider applying for one of these exciting grants. First-time research applicants should seek the advice andexpertise of peers and/or consult with the relevant COSPfor guidance. If you have queries about the applicationprocess, consult the SHPA web site or contact Della Absalom, Assistant to the FederalSecretariat .

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