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PHARMACISTS EDUCATION : Updates and refreshers

High blood pressurewhat

was old is now new again
In the 1980s, hypertension was
trendy and there was a plethora of
new medicines to treat the problem reserpine and methyldopa
had their day. Then came the era of
heart failure, followed by dyslipidaemia for the new century, and
then a holistic approach to cardiovascular risk.
Until recently, high blood pressure was considered as just another
cardiovascular risk factor but, in
the last five years, a bigger focus on
blood pressure has occurred, as the
consequences of high blood pressure have become more evident. A
recent large study of hypertension
from the UK confirms the need to
refocus on high blood pressure.1,2

jOHN DUNLOP

&

LINDA BRYANT

CLINICAL ADVISORY PHARMACISTS

Clinical medication
review

Aetiology
The cause of blood
pressure is largely
unknown and thought to
GROUP 2
be the result of a number
of possible haemodynamic
and pathophysiological disorders.

Learning objectives
To understand the

importance of blood
pressure control.
To recognise the change

Pathology
Early primary hypertension is
not normally associated with pathological changes. Over time, there
is progression to atherosclerosis,
most obviously in the kidney.
Continued hypertension leads
to left ventricular hypertrophy
with coronary, cerebral, aortic,
renal and peripheral vascular
systems being compromised.
High blood pressure does
increase the risk of a cardiovascular event, but also causes end organ
damage, such as renal and retinal

in blood pressure
targets.
To understand the

p harmacological treatment of high blood

pressure.

Figure 1. Hypertension categories

Ambulatory BP mmHg

200
180
160

Masked
hypertension

True
hypertension

True
normotension

White Coat
hypertension

140
120
100
100

PharmacyToday.co.nz

120
140
160
180
Manual office BP mmHg

200

disease, which are costly medical

conditions.
The most important risk for
hypertensives is stroke.
High blood pressure is a difficult cardiovascular risk factor
to treat variable measurement
of blood pressure, a number of
different classes of blood pressurelowering medicines with a variety
of adverse effects, and conflicting
guidelines for first-line therapy.
Is there a target BP?
There is confusion about blood
pressure targets. In New Zealand,
we take a holistic approach to
blood pressure for primary prevention, rather than treating it in isolation, but there is still a tendency
to want to aim for a target blood
pressure.
The recent international guidelines include the Joint National
Committee;3 The American
College of Cardiologists/American
Heart Association;4 the American
Society of Hypertension/
International Society of
Hypertension;5 the European
Society of Hypertension6 and
the NICE guidance. While these
guidelines have been controversial
because of their differences, there
is some consistency.
There has been a relaxation
of target blood pressures, with
most guidelines recommending
a target blood pressure of less
than 140/90mmHg for all people
except those people over 80 years
old in whom the target systolic
blood pressure (SBP) is less than
150mmHg.
The JNC-8 recommends less
than 150mmHg for those older
than 60 years. This relaxation of
blood pressure targets is due to
the lack of evidence of benefit for
lower blood pressure.
A philosophy of lower is better was based on studies such as
the UKPDS study in people with
diabetes, and a lower blood pressure had improved outcomes.7,8
In this study, the mean blood
pressure in the tight control group
was 144/82mmHg compared with
154/87mmHg in the non-tight
control group. The important
aspect of the target though is that it
is less than 140mmHg, not around

about 140mmHg for SBP.

There is also consistency in the
strengthening of the importance of
ambulatory and home blood pressure monitoring in all guides. This
is important due to recognition
of the increased risks of masked
hypertension, white coat hypertension and a lack of night-time blood
pressure.
The older person
There have been two randomised controlled trials investigating blood pressure control
for people over 80 years old with
coronary artery disease.
The INVEST study9 found the
maximal benefit for blood pressure
to be 140/70mmHg for people
over 80, and 135/75mmHg for
those between 69 and 75 years old.
Coronary artery disease appeared
to reduce the tolerance of the very
elderly to low blood pressure.
The mean age of people in the
HYVET study10 was 83.6 years,
with a mean blood pressure of
173/91mmHg. Blood pressure
lowering medicines were a thiazide
and an ACE inhibitor.
Results indicated reducing
systolic blood pressure in the very
elderly from greater than 160
mmHg to a target of 140 mmHg
to 150mmHg is beneficial. Taken
in conjunction with the INVEST
study,7 lower than 140mmHg may
result in detrimental effects.
In terms of extended life
expectancy, a person of 83.6 years
has a remaining expectancy of 1.8
years3 and so maintaining systolic
blood pressure at 140mmHg to
150mmHg extends life by on
average 0.05 years (2.6 weeks).3
Blood pressure-lowering treatment should therefore take into
account other clinical factors for
the patient, such as frailty, adverse
effects and risk of falls.
Another study indicating the
life extension obtained from treating older people is the SHEP study
with a follow-up after 22 years
since the start in 1982. For each
month of treatment, there was a
mean one-day life extension.11
Measuring blood pressure
Blood pressure is variable during the day and dependent on a

number of factors, including the

operator. One-off measures of
blood pressure are not very reliable
and hence the move to ambulatory or home blood pressure
monitoring.
Home blood pressure monitoring
It is important home blood
pressure monitoring is done correctly. It should be done morning
and evening after sitting in a quiet
room for at least five minutes, with
the arm and back supported and
the cuff at the level of the heart.
This is done for seven days, and
the blood pressure for days two
to seven is averaged, and should
be less than 135/85mmHg, which
equates to an office measurement
of less than 140/90mmHg.
Ambulatory blood pressure
monitoring
An advantage of 24-hour ambulatory blood pressure monitoring is
that it allows a better understanding of the diurnal variation of blood
pressure and helps identify those
people who are not night-time
dippers, ie, their blood pressure
does not reduce overnight. Nondippers are more likely to experience cardiovascular events and end
organ damage.
Masked and white coat
hypertension (Figure 1)
Masked hypertension, which
is an office systolic blood pressure less than 140mmHg but high
ambulatory blood pressure, is
increasingly recognised as having a
higher cardiovascular event rate.
For 1000 people during one
year, 11 normotensive will have
a cardiovascular event; 12 people
with white-coat hypertension, 25
people with uncontrolled hypertension and 30 people with masked
hypertension.12
Masked hypertension is associated with younger males, diabetes,
renal disease and a family history of
high blood pressure. It occurs in 12
to 15% of the population.
Non-pharmacological therapy
Weight reduction by 5kg
approximately reduces SBP approximately 4mmHg. Restricting
Continued on page 30
August 2014 | 29

CLINICAL PRACTICE : Updates and refreshers

From page 29
sodium from about 10g to about
5g daily reduces SBP 4mmHg to
5mmHg for those with high blood
pressure, and about 1mmHg for
those with normal blood pressure.
Thirty minutes of activity a
day may reduce SBP 4mmHg to
9mmHg.
Blood pressure-lowering
medicines reduce blood pressure
10mmHg to 15mmHg.

Table 1. Benefits of treating with a thiazide instead

of the comparator

Treatment
The guidance around which
blood pressure medicine to use is
conflicting, but the bottom line is
to get SBP below 140mmHg, and
it is likely that a combination of
blood pressure-lowering medicines
will be necessary.
Thiazides
Thiazides are still very valuable
blood pressure-lowering medicines
and are underused. The ALLHAT
study13 is a crucial study indicating
there was no significant difference
in cardiovascular events or allcause mortality between chlorthalidone, an ACE inhibitor (lisinopril) or a calcium channel blocker
(amlodipine). Chlorthalidone was
significantly better than lisinopril
in preventing the development of
angina, stroke and heart failure,
and significantly better than a calcium channel blocker for preventing heart failure (Table 1).
ACE inhibitors
ACE inhibitors are particularly
effective for people with microalbuminuria, post-myocardial infarction and heart failure. For the up
to 5% of people who need to discontinue an ACE inhibitor due to
cough, an angiotensin II antagonist
is suitable. Adverse renal effects
generally outweigh any benefit of
using an ACE inhibitor and angiotensin II antagonist together.
Calcium channel blockers
Dihydropyridine calcium
channel blockers are effective for

Medical condition

Comparator
(to chlorthalidone)

Number needed to treat

for five years to prevent
the development of the
medical condition

Combined CVD

ACE inhibitor

42

Angina

ACE inhibitor

100

Stroke

ACE inhibitor

143

Heart failure

ACE inhibitor

100

Heart failure

Calcium channel blocker

40

lowering systolic blood pressure.

Swollen ankles appears to be
the most limiting adverse effect,
and these swollen ankles do not
respond well to diuretics.
Discontinuation is required if
the patient finds swollen ankles
unacceptable.
Spironolactone
With a reprisal of renal denervation there was a need to define
resistant hypertension, and then
define the maximal therapy.
The definition is SBP of
160mmHg despite compliance
with three or more antihypertensive drugs (including a thiazide).
The SYMPICITY HTN-3 study
showed no significant difference
between renal denervation and
medicines-based management, but
this has emphasised the optimal
use of blood pressure lowering
medicines and, in particular, the
re-emergence of spironolactone
as an important blood pressure
lowering medicine that we have
neglected lately.
A meta-analysis found that
spironolactone may reduce systolic blood pressure by a mean of
20mmHg, with a dose response
effect up to spironolactone 50mg
daily.14
There is increasing evidence
spironolactone may reduce microalbuminuria.15
Start at spironolactone at
12.5mg daily and titrate up
to 50mg four to six weekly,

Atrial Fibrillation
A200 AFIB

and blood pressure

screening in a click

The Microlife A200 AFIB Blood

Pressure monitor has exclusive patented technology
that simultaneously measures blood pressure and detects
Atrial Fibrillation, enabling people to be referred for diagnosis.

HYPERTENSION and ATRIAL FIBRILLATION (AF) are major risk factors for STROKE
AF is responsible for 15 - 20% of all STROKE cases1
AF increases the risk of stroke 5 times2
30% of New Zealanders with AF (approximately 10,000 people) have no symptoms1,3
3 out of 4 AF related strokes can be prevented if you are already diagnosed4
Always follow the manufacturers instructions and use as directed
References: 1. Kirschof, P. et. al., How can we avoid a stroke crisis? 2009. http://www.escardio.org/communities/EHRA/publications/papersinterest/Documents/ehra-stroke-report-recommend-document.pdf 2. European Heart Rhythm, A., et.al., Guidelines for the Management
of atrial fibrillation: the Task Force for the Management of Atrial Fibrillation of the European Society of Cardiology (ESC). Eurospace, 2010.
12: p1360-420 3. Management of atrial fibrillation in general practice. BPJ, 2011. 39: p22-29. 4. National Stroke Association, Atrial
fibrillation (Afib) and stroke. 2009. http://www.stroke.org/site/DocServer/NSAFactSheets_Afib_9-09.pdf?docID=4901

For further details contact:

Jackel NZ Ph: 0800 877 876
Cons 970-07-14

30 | August 2014

TAPS Approval No: PP5394

Table 2. Risk factors for

hyperkalaemia when using
spironolactone
Creatinine clearance less than
45ml/min
Age over 75 years
Serum potassium concentration over
5mmol/L

monitoring serum potassium,

sodium and creatinine at baseline,
one, two, four, eight, 12 and 24
weeks (Table 2).
Beta-blockers are still valuable
in the presence of comorbidities,
such as angina, previous myocardial infarction and heart failure,
but are no longer first-line therapy,
particularly in the older person.
How can pharmacists help?
Pharmacists can help by
encouraging adherence to blood
pressure medicines and, for suitable people, self-monitoring of

blood pressure. Ongoing reinforcement of lifestyle options is also

helpful, though remember to be
realistic about the level of blood
pressure reduction that can be
realistically expected with lifestyle
changes. n
References
1. Rapsomaniki E, Timmis A, George J et al.
Blood pressure and incidence of twelve
cardiovascular diseases: lifetime risks,
healthy life-years lost, and age-specific
associations in 1.25 million people. The
Lancet 2014;383(9932):1899911.
2. Falaschetti E, Mindell J, Knott C et al.
Hypertension management in England: a
serial cross-sectional study from 1994 to
2011. The Lancet 2014;383:19129.
3. James P, Oparil S, Carter B et al. Evidencebased guideline for the management
of high blood pressure in adults: report
from the panel members appointed to the
eighth Joint National Committtee (JNC
8). JAMA 2014;311:50720. doi:10.1001/
jama.2013.284427
4. Go A, Bauman M, Coleman King S et al. An
effective approach to high blood pressure
control: a Science advisory from the
American Heart Association, the American
College of Cardiology and the Centers for
Disease Control and Prevention. Hypertension 2014;63:878-85.
5. Weber M, Schiffrin E, White W et al.
Clinical practice guidelines for the management of hypertension in the community.
A statement by the American Society of
Hypertension and the International Society
of Hypertension. J Hypertens 2014;32:315
6. Mancia G, Fagard R, Narkiewicz et al.
2013 ESH/ESC guideline for the management of arterial hypertension. Eur Heart J
2013;31:192538. Doi: 10.1093/eurheartj/
eht.151

7. UKPDS study Group. Tight blood pressure

control and risk of macrovascular and
microvascular complications in type 2 diabetes: UKPDS 38. UK Prospective Diabetes
Study Group. BMJ 1998;317:70313.
8. Holman R, Paul S, Bethel M et al. Longterm follow-up after tight control of blood
pressure in type 2 diabetes. N Engl J Med
2008;359:156576.
9. Denardo S, Gong Y, Nichols W et al. Blood
pressure and outcomes in very old hypertensive coronary artery disease patients: An
INVEST substudy. Am J Med 2010;123:719
26.
10. Beckett N, Peters R, Fletcher A et al. Treatment of hypertension in patients 80 years of
age and older. NEJM 2008;358:188798.
11. JKostis JB1, Cabrera J, Cheng JQ et al.
Association between chlorthalidone treatment of systolic hypertension and long-term
survival. JAMA 2011;306:258893.
12. Bobrie G, Chatellier G, Genes N et al.
Cardiovascular prognosis of masked
hypertension detected by blood pressure
self-measurement in elderly treated hypertensive patients. JAMA 2004;291:134249.
13. ALLHAT Officers and Coordinators for the
ALLHAT Collaborative Research Group. Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting
enzyme inhibitor or calcium channel blocker
vs diuretic: The Antihypertensive and LipidLowering Treatment to Prevent Heart Attack
Trial (ALLHAT). JAMA 2002;288:298197.
14. Batterink J, Stabler S, Tejani A et al.
Spironolactone for hypertension. Cochrane
Database Syst Rev 2010;8:CD008169.doi:
10.1002/14651858.CD008169.pub2
15. Oxlund C, Henriksen J, Tarnow L et al. Low
dose spironolactone reduces blood pressure
in patients with resistant hypertension
and type 2 diabetes mellitus: a double
blind randomised clinical trial. J Hypertens
2013;31:2094102.

Pharma companies reporting

more reactions in Australia
Denise Piper

Pharmaceutical companies are

reporting an increasing number
of adverse reactions in Australia,
where reporting is compulsory.
A report by Australias
Therapeutic Goods Administration
(TGA) shows 17,500 total reports
of medicine and vaccine adverse
events in 2013.
Of these, 55% (9563) were
filed by sponsors companies
responsible for the supply and
manufacture of pharmaceuticals
and vaccines.
The rest came from health
departments after immunisation (17%), hospitals and hospital
pharmacists (10%), community
pharmacists (7%), GPs (4%) and
consumers (3%).
Health professionals are
encouraged to report suspected
adverse events directly to TGA,
although they can also report
directly to the manufacturer or
sponsor, the TGA report says.
However, sponsors are required
to report any adverse reactions.
The number of reports made

by sponsors has steadily increased

over the past five years, more than
double since 2009, the report says.
But Medicines New Zealand
says, while the overall number
of adverse events reported has
increased, this is potentially attributable to the Australian pharmacovigilance requirements expanding to include non-prescription
medicines.
In New Zealand, it is not
compulsory for pharmaceutical
companies to report adverse reactions, and Medsafe does not record
the percentage of reports filed by
sponsors.
In 2013, there were 4138
reports of suspected adverse reactions reported to New Zealands
Centre for Adverse Reactions
Monitoring.
The number has remained
consistent over the last five years,
according to a Medsafe report.
Of the reports filed by healthcare professionals:
nurses report the most adverse
reactions (39%), followed by
GPs (25%)
hospital doctors (14%)

Reports of adverse reactions are

increasing from pharmaceutical
companies in Australia, but reporting
requirements are different in New
Zealand

hospital pharmacists (7%)

community pharmacists (6%)
the public (2%), plus
others (7%). DP
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