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FATS5
A strategy for the use of cholesterol lowering drugs in
Newcastle, North Tyneside and Northumberland
A summary of the evidence used to develop FATS5 from FATS4
The recommendations are presented in summary form as a quick reference
guide on the last page
FATS Steering Group February 2009
1
INDEX
Page
INTRODUCTION
3
SUPPORTING NOTES
4
People with symptomatic or prior occlusive vascular disease
4
People with diabetes (Type 1 of Type 2), or IGT (OGTT)
12
High risk people without symptomatic or prior occlusive
vascular disease and without diabetes / IGT (OGTT)
15
Additional notes
20
Appendix; Membership of the group
24
Summary form as quick reference guide
26
2
INTRODUCTION
FATS5 has been developed following a review of FATS4. The following have been
published since the development of FATS4 and have been taken into consideration;
 NICE Lipid Modification Guideline, CG0671.
 NICE Guideline for the Management of Type 2 diabetes, CG0662
 NICE Guideline for Chronic Kidney Disease, CG0733.
 NICE Guideline for Identification and Management for familial
hypercholesterolaemia, CG0714
 Important statin trials published / presented since the NICE lipid modification
guideline.
As in previous iterations of the FATS guidelines, FATS5 not only incorporates new
evidence, but also considers how the guideline will be implemented. The aim has
been to provide a practical tool drawing on the evidence of clinical and cost
effectiveness, which can be used in everyday practice. The FATS group recognised
that occasional people as a result of their specific lipid abnormalities, drug
intolerances and co-morbid conditions may need to be managed outside the
guidelines, but this will usually be following specialist advice, and the reasons should
be explicitly stated.
FATS5 is intended for all clinicians in the Newcastle, North Tyneside,
Northumberland areas involved in treating people for primary and secondary
prevention of cardiovascular disease, including coronary disease, cerebro-vascular
disease and peripheral arterial disease.
How to use the FATS5 guideline
The guideline has two parts; the summary part, a quick reference guide which can be
easily folded over and laminated into a double sided A5 sheet and kept readily
available, is at the end of the supporting notes.
The notes contain each of the recommendations in the summary highlighted in bold
in text boxes with background detail of how the decision to include the
recommendation was reached, and in some cases expand the recommendation
providing more detailed guidance.
The summary is intended as a quick reference guide and an everyday reminder. The
notes contain additional supporting information and clinicians are encouraged to be
familiar with these and use them to refer to for further clarification of management in
individual people as needed. The BNF should be referred to as necessary.
1
http://www.nice.org.uk/Guidance/CG67/NiceGuidance/pdf/English
http://www.nice.org.uk/nicemedia/pdf/CG066NICEGuidelineCorrectedDec08.pdf
3 http://www.nice.org.uk/nicemedia/pdf/CG073NICEGuideline.pdf
4 http://www.nice.org.uk/nicemedia/pdf/CG071NICEGuideline.pdf
2
3
SUPPORTING NOTES
FATS5 is a lipid lowering drug strategy which should only be used within an overall
lifestyle and clinical management strategy
It is assumed that people with contraindications to specific drugs will be identified and
excluded (refer to the BNF).
Statins and fibrates are contra-indicated in pregnancy. In all women in whom
pregnancy is possible, the following should be specifically clarified before
starting treatment; whether pregnant, contraceptive status and future
pregnancy plans or possibility of pregnancy.
PEOPLE WITH SYMPTOMATIC OR PRIOR OCCLUSIVE VASCULAR DISEASE
All people with symptomatic or prior occlusive vascular disease should be considered
for lipid lowering drugs. This is consistent with FATS4 and with relevant NICE
guidance. Occlusive vascular disease includes people with coronary heart disease,
atheromatous stroke disease and people with peripheral arterial disease.
Measure lipid profile (total cholesterol, HDL cholesterol, triglycerides)
This is the same as in FATS4. The NICE lipid modification guideline recommends at
least one fasting sample be measured and it was agreed that a fasting sample was
preferred, but not mandatory and a non-fasting sample was acceptable. It is
important to measure a full lipid profile including total cholesterol, HDL cholesterol
and triglycerides. LDL cholesterol can only be calculated from a fasting sample.
However, non-HDL cholesterol can be calculated from a non-fasting sample and may
be used to monitor the response to treatment. If non-fasting triglyerides are markedly
raised (> 4.5 mmol/l), a fasting sample is required for an accurate assessment.
All people presenting with ACS/acute MI should also have a full lipid profile
measured on presentation, taking note of the timing of the sample from the onset of
symptoms. The NICE lipid modification guideline did not recommend measuring a
lipid profile prior to starting treatment in people with ACS/acute MI, but the FATS
group felt that it was important to do so. Interpretation of the result should be made
taking into account the duration from onset of symptoms. Studies have shown that
lipid profiles taken in the first 6 to 12 hours after the onset of an acute MI are
reflective of the patients’ baseline steady state lipid levels. After that time frame an
acute phase response occurs, with a fall in total and LDL cholesterol levels. This can
decrease the LDL cholesterol levels by as much as 50%. However, this fall does not
protect from atherosclerosis as the acute phase response makes the LDL cholesterol
more prone to oxidation and the HDL cholesterol pro-inflammatory. Following an
acute MI, it can take up to 6 weeks for the lipid levels to return to baseline. Thus, a
non fasting sample obtained on or shortly after admission can be used to assess the
patients baseline lipid status, and aid in diagnosing lipid abnormalities. Lipid profiles
taken 24 hours to 6 weeks after the onset of MI should be interpreted knowing that
the usual LDL cholesterol may be as much as twice the measured value.
4
Measure ALT or AST at baseline (and after 3 months if high dose statin)
No change from FATS4 in patients treated with simvastatin 40 mg od or other
low/moderate dose statins, but an additional recommendation to measure liver
enzymes after 3 months in those treated with high dose statins (ie simvastatin 80 mg
od, atorvastatin 80 mg od).
The FATS group discussed the recommendation in the NICE lipid modification
guideline to measure LFTs at baseline, 3 months and 12 months in all patients. The
evidence statements informing this recommendation were;
6.3.1.5 In a systematic review of cohort studies, randomised trials, voluntary
notifications to regulatory authorities and published case reports, the incidence of
major adverse events associated with skeletal muscle and the liver was low.
6.3.1.8 Elevations of the liver enzymes alanine aminotransferase and / or aspartate
aminotransferase were reported more frequently in those treated with statins
compared with placebo, especially at higher doses. Trials showed no excess of liver
disease or chronic kidney disease in statin allocated participants.
The NICE lipid modification guideline also acknowledged that there was little
evidence to support the recommendation to monitor LFTs in all patients and that this
was reached by consensus. However, there is evidence of an increased risk of a
sustained rise in liver enzymes in patients treated with high dose statins.
FATS5 recommends checking LFTs (ALT or AST) at baseline to identify those with
raised levels before initiating treatment, but only recommends routine monitoring
after 3 months in those treated with high dose statins. FATS5 also emphasises that if
liver enzymes are abnormal during monitoring, the test must be repeated before any
action based solely on the results of the blood test is taken. In many cases the
abnormality may not be sustained, and the statin can be safely continued.
The main purpose of measuring ALT or AST before treatment is to identify people
with abnormal results prior to starting drug treatment, but not to exclude them from
treatment. Fatty liver is one cause of a raised ALT/AST and is certainly not an
indication to exclude people from treatment.
Members of the FATS group felt that statins were sometimes inappropriately stopped
in people who develop abnormal LFTs, and clinical status, repeat blood testing and
other causes of abnormal LFTs should be considered before statins are stopped.
In some people with raised liver enzymes a lower dose of statin may be started
initially, and liver function may be monitored during treatment. The locally available
liver enzyme assay should be used.
5
If ALT or AST < 2 fold normal, prescribe a statin as below
This is consistent with FATS3 and FATS4, and is based on the recruitment criteria to
the Heart Protection Study. In some people with raised liver enzymes a lower dose of
statin may be started initially, and liver function may be monitored during treatment.
The FATS group emphasised that people with raised liver enzymes should not be
automatically excluded from statin treatment.
In acute coronary syndrome/ acute MI ;
In all others;
Atorvastatin 80mg od
Initiate simvastatin 40mg od
Consider titration to simvastatin 80mg od (benefits/risks)
Repeat lipid profile 8 weekly until TC < 4 mmol/l, LDL-C (fasting) < 2 mmol/l,
or non-HDL-C < 2.8 mmol/l or maximum drug flow reached (see supporting
notes)
People intolerant of recommended statin; see supporting notes
Background evidence
There is good clinical evidence that in people with coronary disease higher intensity
statins and hence greater proportional reductions in LDL cholesterol, compared with
lower intensity statins, are associated with a reduction in major vascular events. The
NICE lipid modification guideline has analysed the cost effectiveness of higher
intensity statins in different sub-groups, and concluded that treatment with either
simvastatin 80 mg od or atorvastatin 80 mg od is cost effective when this is initiated
in people with a spontaneous acute coronary syndrome / acute MI.
In people with established vascular disease (see above if ACS/acute MI, see below if
diabetes), it is cost effective with current pricing in the setting of secondary
prevention to titrate to simvastatin 80 mg od when treated with simvastatin 40 mg
daily to achieve a target total cholesterol of 4 mmol/l. In people without diabetes it is
not cost effective to use a non-generic statin.
Health economic analysis in the NICE type 2 diabetes guideline found that in people
with type 2 diabetes and known vascular disease it was cost effective to further titrate
to atorvastatin 80 mg od if total cholesterol remained > 4 mmol/l or LDL cholesterol
remained > 2 mmol/l when treated simvastatin 80 mg od.
FATS5 does not make recommendations for treating people with familial
hypercholesterolaemia in whom a non-generic statin may be required – see the NICE
guideline for familial hypercholesterolaemia, CG071.
Acute coronary syndrome / MI in FATS5
The FATS group discussed whether people with an acute coronary syndrome / acute
MI should be treated with simvastatin 80 mg od or atorvastatin 80 mg od. No
published trials in people with acute coronary syndrome / acute MI have initiated
6
simvastatin 80 mg od, (A-Z5 titrated after a month), whilst PROVE-IT6 initiated
atorvastatin 80 mg od. The cost impact with atorvastatin 80 mg is higher than with
simvastatin 80 mg od, but the number of people to be treated is relatively small and
the patent expiry for atorvastatin is November 2011. The group also considered the
results of SEARCH7, a randomised trial of simvastatin 20 mg od compared to
simvastatin 80 mg od in people with a past history of MI. The (non-peer reviewed),
results indicate a higher incidence of myopathy and rhabdomyolysis with simvastatin
80 mg od compared to that reported in clinical trials with atorvastatin 80 mg od.
The consensus was to recommend early use of atorvastatin 80 mg od in people
presenting with an acute coronary syndrome / acute MI, taking into account any
potential interactions / increased risk of adverse side effects. Further titration is not
recommended, although lipids should be monitored. There is no recommendation to
routinely reduce the dose after an interval.
People without acute coronary syndrome / MI in FATS5
In people with vascular disease who do not present with an acute coronary
syndrome/ acute MI, treatment should be initiated with simvastatin 40 mg od, with
titration to simvastatin 80 mg od being considered if necessary to achieve a total
cholesterol < 4 mmol/l, LDL cholesterol < 2 mmol/l or non-HDL cholesterol < 2.8
mmol/l. Reductions in total and LDL cholesterol with simvastatin 40 mg od and
simvastatin 80 mg od (summary estimates from 164 randomised controlled trials)
were included in the full version of the NICE lipid modification guideline8;
Statin
Daily
dose
(mg)
Absolute total
cholesterol
reduction (95% CI)
mmol/l
Simvastatin
Simvastatin
40
80
2.14 (1.99-2.28)
2.41 (2.20-2.63)
% reduction
in total
cholesterol
(95% CI)
mmol/l
31%
35%
Absolute LDL-C
reduction (95%
CI) mmol/l
% reduction
in LDL-C
(95% CI)
mmol/l
1.78 (1.66-1.90)
2.01 (1.83-2.19)
37%
42%
The group discussed the results of SEARCH1 which had been presented, but not
published. The group took note of the reported incidence of myopathy in people
treated with simvastatin 80 mg od, particularly during the first year. The group
reached the consensus that before considering titration the likely benefits of the dose
increase and the risk of adverse effects should be taken into account. In some
people, in whom the risk of treatment with simvastatin 80 mg od may be higher and
the benefits lower, treatment with simvastatin 40 mg od may be continued rather than
making any titration.
Thus in those not achieving a total cholesterol < 4 mmol/l, LDL cholesterol < 2 mmol/l
or non-HDL cholesterol < 2.8 mmol/l, the following should be considered;

The initial response in the lipid profile to treatment with simvastatin 40 mg od, and
the likely benefits of further titration to simvastatin 80 mg od.
5
JAMA 2004;292:1307-1316
NEJM 2004;350:1495-1504
7 http://www.ctsu.ox.ac.uk/search/ accessed 9/1/2009
8 http://www.nice.org.uk/nicemedia/pdf/CG67FullGuideline1.pdf accessed 9/1/2009
6
7

The likely risk of adverse side effects from increasing the dose to simvastatin 80
mg od.
The risk of adverse side effects, particularly myopathy/rhabdomyolysis with high dose
simvastatin, should be informed by an assessment of;



The development of any mild myalgia taking simvastatin 40 mg od
The presence of some co-morbidities (see below)
Treatment with other drugs which interact (see below)
Further information about co-morbidities and drug interactions is given in the
‘Additional notes below’. The BNF should also be referred to.
Patients treated with simvastatin 80 mg od should be reviewed to assess the
additional response from the increased dose, and ensure there has been additional
demonstrable benefit and maintaining the higher dose is justified.
A lower dose of simvastatin may be considered initially in people with co-morbidity
which increases the risk of adverse side effects or who are taking other drugs which
interact with simvastatin. In some cases the maximum dose may also be lower.
Statin intolerance
The FATS group also further discussed the issues of tolerability and efficacy, and
recognised the importance of equitable access to treatment. In FATS5 people
intolerant of simvastatin, alternative statins, of similar cost, such as pravastatin, can
be considered as recommended by the NICE lipid modification guideline. In some the
addition of ezetimibe to lower dose generic statin may be needed as recommended
by the NICE technology appraisal guidance, TA132, ‘Ezetimibe for the treatment of
primary (heterozygous familial and non familial) hypercholesterolaemia’, although this
has a higher acquisition cost at present. Pravastatin is not as efficacious in terms of
cholesterol lowering, but seems better tolerated by some people than simvastatin.
Tolerability includes people who develop adverse side effects as well as those
treated with other drugs which interact with higher dose simvastatin. This is
consistent with the NICE lipid modification guideline which recognises the need to
consider patient preferences, co-morbidities, other drug treatment, and benefits and
risks of treatment.
People intolerant of any statin should be assessed on an individual basis. A fibrate
(fenofibrate is recommended) may be considered. The recommended initial dose is
one capsule of Lipantil Micro 200 daily with food. Patients with more severe
dyslipidaemia may require an increased dose of 267 mg daily (Lipantil Micro 267),
which should always be taken with food as it is less well absorbed from an empty
stomach. The dose should be reduced in patients with renal impairment (refer to the
BNF, but in brief reduce dose to 2x67 mg capsules if eGFR < 60 ml/min/1.73m 2, and
to one 67 mg capsule if eGFR is < 20 ml/min/1.73m2, avoiding altogether if the eGFR
is less than 10 ml/min/1.73m2). However, those people who have had a serious
adverse reaction to a statin such as rhabdomyolysis should be referred to a lipid
clinic for assessment first, if this is being considered. Ezetimibe 10 mg od is an
alternative. There is far less clinical outcome data with either of these drugs than
8
there is with statins. The table below includes estimates of the average change in
total and LDL cholesterol with the two drugs.
Drug
Fenofibrate 267 mg daily
Ezetimibe 10 mg daily
Mean change total cholesterol
- 22%
- 13%
Mean change LDL cholesterol
- 26%
- 19%
Treatment with the combination of a fibrate and ezetimibe is not a licensed indication,
although has been shown to be effective in a published clinical trial and may be
considered in some circumstances.
Higher risk people
Higher risk people ie diabetes, disease in > 1 arterial bed (CHD,
cerebrovascular, PAD), after CABG or recurrent spontaneous acute CVD
events within a year, consider titration to atorvastatin 80 mg od / simvastatin
40 mg plus ezetimibe 10 mg; see supporting notes
The NICE lipid modification guideline reported that in people not presenting with an
acute coronary syndrome / acute MI, routine titration beyond simvastatin 80 mg od is
not cost effective. However, the NICE lipid modification guideline does not address
the management of people with diabetes, and health economic analysis reported in
the NICE guideline for the management of type 2 diabetes found that titration to
atorvastatin 80 mg, if a total cholesterol < 4 mmol/l or LDL cholesterol < 2 mmol/l is
not reached, was cost effective in people with type 2 diabetes and established
vascular disease. The Markov model reported in the NICE type 2 diabetes guideline9
assumed the risk of developing cardiovascular disease events in people with type 2
diabetes compared with non-diabetics was 1.9 fold. Evidence from the literature
suggested the risk could be between 1.5 to 2.6 fold and in a sensitivity analysis the
risk of developing cardiovascular disease events has to be at least 1.6 fold for twostep titration (to atorvastatin 80 mg od) to a total cholesterol < 4 mmol/l to be costeffective at £20,000/QALY.
People with type 2 diabetes and established vascular disease are a higher risk
group, and whilst titration to atorvastatin 80 mg od is not cost effective in ‘average
people without diabetes’ being treated for secondary prevention, there will be some
in whom the absolute risk is similar to that of people presenting with acute coronary
syndrome/ acute MI, or of those with type 2 diabetes and established vascular
disease. The FATS group felt that by extrapolation, titration in such people could be
anticipated to be cost effective, and agreed to recommend titration to atorvastatin 80
mg od be considered in such people if total cholesterol remains ≥ 4 mmol/l, LDL
cholesterol ≥ 2 mmol/l or non-HDL cholesterol ≥ 2.8 mmol/l. These people are strictly
defined as those in the following groups: with diabetes, or with disease in more than
1 arterial disease location (coronary disease, cerebrovascular disease and PAD)10, or
9
National Collaborating Centre for Chronic Conditions. Type 2 diabetes: national clinical Guideline for
management in primary and secondary care (update). London: Royal College of
Physicians, 2008. Appendix D accessed www.nice.org.uk on 21/12/2008.
10
Steg PG et al for the REACH Registry One year cardiovascular event rates
in outpatients with atherothrombosis. JAMA 2007;297:1197-1206.
9
after CABG or with recurrent acute events within a year (although these latter people
may already be treated if they have an acute coronary syndrome. In other people
statins should not be routinely titrated beyond simvastatin 80 mg od.
The FATS group discussed the option of titration to atorvastatin 80 mg od or to
simvastatin 40 mg od plus ezetimibe 10 mg od if a two-step titration is being
considered. There is good evidence for efficacy of atorvastatin 80 mg od in reducing
cardiovascular events and this is the recommended option, unless tolerability of high
dose statin is a concern.
Non-HDL cholesterol and assessing response to therapy
This is unchanged from FATS4. Some clinicians may prefer to use non-HDL
cholesterol measurements instead of LDL cholesterol when assessing response to
treatment. Total cholesterol includes the cardio-protective HDL cholesterol fraction,
but it is the atherogenic fraction of total cholesterol, which needs to be the primary
focus for treatment. LDL cholesterol is a major atherogenic fraction of total
cholesterol and is calculated from the Friedewald formula using total cholesterol,
HDL cholesterol and triglyceride. It requires a fasting sample, and is only valid when
triglycerides are below 4.5 mmol/l. In some people (for example those with lower total
and LDL cholesterol levels and those with diabetes), the triglyceride rich lipoprotein
fraction, VLDL, accounts for a greater proportion of serum lipids. When enriched in
cholesterol, VLDL fractions are considered to be atherogenic and use of LDL
cholesterol as a therapeutic target may result in under treatment.
Non-HDL cholesterol includes LDL and VLDL cholesterol. A reduction in non-HDL
cholesterol is associated with a reduction in coronary risk11 and has been proposed
in the US NCEP ATP III guidelines as an alternative to LDL cholesterol as a
therapeutic target12. It has the advantage of not requiring a fasting sample and can
be used in people with raised triglycerides. Non-HDL cholesterol is a simple
calculated measure which is reported alongside LDL cholesterol by the biochemistry
laboratories in Newcastle Hospitals and Northumbria Healthcare Trust and may be
preferred as a therapeutic target.
Some clinicians measure cholesterol alone, and this may be used for monitoring
purposes, but only if HDL cholesterol and triglycerides are known to be normal. A full
lipid profile should always be measured at baseline.
44% of patents had diabetes at baseline and the rate of cardiovascular death, acute MI and stroke at 1
year was 2.15% for patients with at least 3 risk factors only, 3.06% (PAD), 3.64% (coronary artery
disease), 5.54% (cerebrovascular disease) for patients with one, 5.54% (PAD and coronary artery
disease), 7.35% (coronary artery disease and cerebrovascular disease), 7.76% (PAD and
cerebrovascular disease) in patients with two, and 9.21% for patients with three symptomatic arterial
disease locations. The rate of cardiovascular death, MI, stroke or hospitalisation for an
atherothrombotic event at 1 year was 5.31% for patients with at least 3 risk factors only, 17.44%
(PAD), 13.04% (coronary artery disease), 9.87% (cerebrovascular disease) for patients with one,
23.11% (PAD and coronary artery disease), 19.81% (coronary artery disease and cerebrovascular
disease), 21.95% (PAD and cerebrovascular disease) in patients with two, and 26.29% for patients
with three symptomatic arterial disease locations.
11
12
JACC 2009;53:316-322
Although is not included in the NICE lipid modification guidelines
10
Low HDL cholesterol
There is no new evidence for the clinical effectiveness of using drug therapy targeted
at increasing HDL cholesterol and no changes have been made for FATS5, although
the results of HPS2-THRIVE are awaited. In people with low HDL cholesterol, diet
and physical activity should be specifically discussed, but routine initiation of drug
treatment such as modified release nicotinic acid is not currently routinely
recommended. Drug treatment targeted at raising HDL cholesterol per se should only
be prescribed following recommendation from specialist care.
11
PEOPLE WITH DIABETES (Type 1 or Type 2), OR IGT (OGTT)
Statins and fibrates are contra-indicated in pregnancy. In all women in whom
pregnancy is possible, the following should be specifically clarified before
starting treatment; whether pregnant, contraceptive status and future
pregnancy plans or possibility of pregnancy.
Impaired glucose tolerance (IGT) is diagnosed from a 75g oral glucose tolerance test
(OGTT) and the indications for a OGTT are included in the local diabetes guidelines.
People with IGT should be considered to have a similar vascular risk to those with
Type 2 diabetes.
Consider drug treatment in people with;
 Type 1 and Type 2 diabetes with microalbuminuria/proteinuria
 Type 1 diabetes / Type 2 diabetes / IGT aged ≥ 40 years
 Type 1 diabetes / Type 2 diabetes / IGT aged < 40 years if other
cardiovascular risk factors present and using clinical judgement
As in FATS4, all people with diabetes (Type 1 or Type 2) with microalbuminuria /
proteinuria should be considered for statin treatment.
Those with Type 1 diabetes, Type 2 diabetes or IGT aged ≥ 40 years should be
considered for statin treatment unless all of the following are present;
 Not overweight, tailoring this with an assessment of body weight associated risk
according to ethnic group
 Normotensive (<140/80 mmHg in the absence of antihypertensive therapy)
 Does not have microalbuminuria
 Does not, and has not recently, smoked
 Does not have a high-risk lipid profile; ie total cholesterol ≥ 6.0 mmol/l, HDL < 1.0
mmol/l in men, < 1.2 mmol/l in women, fasting triglycerides > 1.7 mmol/l (non-fasting
> 2.5 mmol/l)
 Has no history of cardiovascular disease, and
 Has no family history of premature cardiovascular disease.
Those who are older may still be considered for treatment even if the above are the
case, as cardiovascular risk increases with age.
Assessment of cardiovascular risk in people with Type 1 diabetes, Type 2 diabetes or
IGT aged < 40 years remains difficult, and it was agreed to make a single
recommendation for these people in FATS5. Clinical judgement is required, and
treatment should be considered in those with one or more other cardiovascular risk
factors, with the indications becoming stronger as the number of cardiovascular risk
factors increases, and particularly as people near the age of 40 years.
Cardiovascular risk factors include:
 Family history of premature coronary disease; first degree relative in men< 55
years, women< 65 years)
12
 Of ethnic group with high risk, eg those of South Asian origin
 More severe abnormalities of blood lipids; total cholesterol ≥ 6 mmol/l, HDL < 1.0
mmo/l in men, < 1.2 mmol/l in women, fasting triglycerides > 1.7 mol/l (non-fasting >
2.5 mmol/l)
 Blood pressure ≥ 140/90 mmHg or requiring anti-hypertensive treatment
 Current or recent smoking
 Two or more features of the metabolic syndrome which are;
o Raised blood pressure (requiring anti-hypertensive treatment)
o Excess body fat, particularly abdominal fat – ‘central obesity’ ie BMI ≥
30 kg/m2, or BMI < 30 kg/m2 with increased waist circumference
(Caucasian men ≥ 102 cm (40 in), women ≥ 88 cm (35 in), Asian men
≥ 90 cm (35 in), women ≥ 80 cm (32 in))
o Low HDL-cholesterol (< 1.0 mmol/l in men and < 1.2 mmol/l in women)
o High triglycerides (fasting triglycerides > 1.7 mmol/l, non-fasting
triglycerides > 2.5 mmol/l)
A non-fasting triglyceride level has been included for those in whom fasting samples
may be particularly difficult to obtain.
It was noted that some features of the metabolic syndrome are alone also included
as cardiovascular risk factors.
Drug flow;
Simvastatin 40 mg od
Consider simvastatin 80 mg od (benefits/risks)
Atorvastatin 80 mg od / simvastatin 40 mg plus ezetimibe
10 mg od only if established CVD
Threshold for titration and additional notes see other sections
The NICE guideline for management of type 2 diabetes reports that initiation of
simvastatin 40 mg od with a 1 step titration to simvastatin 80 mg od if total
cholesterol remains above 4 mmol/l, LDL cholesterol > 2 mmol/l is cost effective in
people with type 2 diabetes without known symptomatic vascular disease, but that a
2 step titration to atorvastatin 80 mg od is not. However, in people with type 2
diabetes who have established vascular disease a second titration to atorvastatin 80
mg od is cost effective.
If total cholesterol remains ≥ 4 mmol/l, LDL cholesterol ≥ 2 mmol/l, non-HDL
cholesterol ≥ 2.8 mmol/l when treated with simvastatin 40 mg od, FATS5
recommends titration to simvastatin 80 mg od, but with a second titration to
atorvastatin 80 mg od only in those with established vascular disease. Titration to
simvastatin 80 mg od should take into consideration the benefits and risks of this. In
people intolerant of simvastatin other statins may be considered. Refer to the section
entitled ‘People with symptomatic or prior occlusive vascular disease’.
13
Type 2 diabetes and triglycerides > 1.7 mmol/l < 10 mmol/l; therapeutic
lifestyle measures for 6 months then consider adding a fibrate (see
supporting notes)
Previous iterations of FATS have not recommended combinations of statins and
fibrates unless recommended by specialist care. The NICE guideline for the
management of Type 2 diabetes recommends a combination of a statin and a fibrate
be considered in people with diabetes if triglycerides are raised. The FATS group
discussed this and came to the following consensus;








If triglycerides are > 10 mmol/l seek specialist advice, eg by phone, as these
people are at risk of acute pancreatitis.
Look for and address secondary causes of high triglycerides, including poor
glycaemic control, (others include untreated hypothyroidism, renal impairment and
liver inflammation, particularly from alcohol) and make recommendations for
intensive therapeutic lifestyle interventions (diet, alcohol reduction and physical
activity).
Consider treatment with a combination of statin and fibrate if fasting triglycerides
remain > 4.5 mmol/l, or if fasting triglycerides are between 2.3 and 4.5 mmol/l if
known cardiovascular disease or particularly high cardiovascular disease risk. The
BNF recommends adding a fibrate to a statin after 6 months of therapeutic lifestyle
interventions, if triglycerides remain high and it was agreed to adopt this time
interval.
A fasting lipid profile should be measured prior to considering combination
treatment. However, raised triglycerides may be noted on an initial non fasting
sample, and treatment with a statin, lifestyle interventions, and optimising
glycaemic control could be initiated with the aim of arranging a fasting sample at
the 6 month assessment when, if triglycerides remain raised, a fibrate might be
added.
It was recognised that whilst it is ideal that glycaemic control is optimised prior to
treating with the combination of a statin and fibrate, this is not always achievable
(although should be aspired to).
Fenofibrate (such as 200 mg micronised fenofibrate) is the preferred fibrate, and if
combined with a statin this should only be simvastatin 40 mg od, not higher
intensity statins such as simvastatin 80 mg od or atorvastatin 80 mg od (unless
following specialist recommendation). It was noted that fenofibrate has some LDL
cholesterol lowering effect, which will offset the impact of any reduction in the dose
of the statin. Higher doses of fenofibrate are not recommended in combination with
a statin.
Gemfibrozil should not be prescribed in combination with a statin (increased risk
of myopathy).
The combination of a statin and fibrate is associated with an increased risk of
adverse effects, and this should be taken into account when considering whether
to initiate combination therapy.
14
HIGH RISK PEOPLE WITHOUT SYMPTOMATIC OR PRIOR OCCLUSIVE
VASCULAR DISEASE AND WITHOUT DIABETES / IGT (OGTT)
FATS advice is based on risk not cholesterol, discuss risk not just cholesterol
Overall vascular risk should be discussed, not just cholesterol. Clinicians should
consider carefully how they are going to do this with people and the tools they will
use to support the discussion.
In people at high risk of developing vascular disease
Measure total and HDL cholesterol, triglycerides (non-fasting acceptable)
A non-fasting sample is acceptable, but as above a fasting sample is required to
accurately assess triglycerides, and for calculation of LDL cholesterol.
A cholesterol cannot be interpreted in isolation when assessing people for primary
prevention and a full lipid profile must be measured.
Estimate 10 year CVD risk (Framingham)
There are different cardiovascular risk assessment tools available. The NICE lipid
modification guideline recommends adopting a risk assessment tool based on
Framingham. QRISK was discussed by the FATS group, but the consensus was to
recommend Framingham risk assessment as the preferred option, although
acknowledging other risk assessment methods exist.
Any initial cardiovascular risk assessment should incorporate;
 Age
 Gender
 Total to HDL cholesterol ratio (prior to treatment)
 Blood pressure (prior to treatment)
 Smoking status
A total to HDL cholesterol ratio and blood pressure before treatment may not always
be available. In this case, available measurements should be used, recognising that
the calculated risk will be lower than if pre-treatment levels had been used, and
clinical judgement used to incorporate this into the overall assessment.
If definite LVH on ECG, double 10 year CVD risk (if not already included)
In people with hypertension an ECG is required to look for left ventricular hypertrophy
(LVH). Some risk calculators may already include LVH in the 10 year CVD risk
estimate, but if not, the 10 year CVD risk estimated from the risk factors age, gender,
total cholesterol to HDL cholesterol ratio, blood pressure and smoking status should
be doubled. Possible LVH on an ECG is not an indication to double the risk.
15



Possible ECG-LVH with only voltage criteria for LVH is not associated with a
marked excess vascular risk over and above that associated with the raised blood
pressure, and should not be included as an additional factor in the risk
assessment.
Definite ECG-LVH with ST depression / T wave flattening or more marked ST / T
wave changes as well as increased voltages is associated with a significantly
increased risk, independent of the raised blood pressure, and should be included
as an additional risk factor in the risk assessment.
If the significance of the voltages on an ECG is uncertain, the ECG might be
repeated after 2 years looking for progression of ECG changes of LVH and thus
an increased risk, particularly if this would lead to a change in treatment.
In the Framingham Study, the criteria for definite ECG-LVH included some, but not
all, of the following:
 an increased R wave amplitude in leads reflecting potentials from the left ventricle
associated with S-T segment depression and T wave flattening or inversion;
 deep S waves over the right precordial leads;
 left axis deviation (> - 30 degrees);
 prolongation of the QRS complex duration;
Possible ECG-LVH was defined if tracings showed similar abnormalities which were
less marked and for which the principal findings included in this category were
increased R wave amplitude without prominent ST and T wave abnormalities13.
After adjustment for blood pressure, vascular risk became markedly attenuated or
disappeared in those with possible ECG-LVH. In those with definite ECG-LVH, the
four fold increased risk was reduced by about 25% after adjustment for blood
pressure14.
People with the greatest increases in voltages and those with the most marked
repolarisation changes are at greatest risk15. Serial change in voltages and
repolarisation changes also predicted future risk, with a reduction associated with a
lower risk and an increase with a higher risk16.
Consider other additional risk factors:
Family history of premature CHD (men< 55 yrs, women< 65 yrs)
South Asian origin
Fasting triglycerides > 1.7 mmol/l
High level of deprivation
Premature female menopause aged ≤ 45 years
Other conditions (eg CKD, inflammatory arthritis, connective tissue
disease, severe mental illness, other severe inflammatory conditions)
The current national recommendation is to consider statin treatment in people with a
10 year cardiovascular disease risk of 20% or more. In addition to the conventional
13
Kannel WB Ann Intern Med 1970;72:813
Kannel WB Ann Intern Med 1970;72:813
15 Levy D Circulation 1994;90:1786-1793
16 Levy D Circulation 1994;90:1786-93
14
16
risk factors used in the Framingham assessment, other factors increase
cardiovascular risk. These include the factors above.
The presence of other co-morbid conditions such as CKD, inflammatory arthritis,
connective tissue disease, and severe mental illness increase cardiovascular risk.
Other inflammatory conditions may be associated with an increased risk, and for
example, people with severe psoriasis which requires systemic treatment may also
have a higher risk. People with HIV also have a heightened cardiovascular disease
risk, but drug treatment needs tailoring (avoiding simvastatin because of drug
interactions).
It was uncertain how useful the FATS4 recommendation to add 5% to an initial
cardiovascular risk assessment had been if additional markers of risk were present.
The NICE lipid modification guideline recommends that the risk is 1.5 fold higher with
a family history of premature coronary heart disease with one family member affected
and between 1.5 and 2.0 fold higher if more than one family member is affected.
The NICE lipid modification guideline distinguishes South Asian men from South
Asian women and recommend an incremental risk only in men, recommending a 1.4
fold increased risk. The FATS group further considered the available evidence and
agreed that both men and women of South Asian origin should be considered as
being at increased risk.
There was general agreement that clinical judgement was required. An initial risk
assessment should be made using conventional risk factors, incorporating additional
risk factors using clinical judgement. For example, a statin would be recommended in
a patient with an initial 10 year cardiovascular disease risk of 18% if there was also
an additional risk factor such as a family history of premature coronary heart disease.
As a general guide, a statin should be considered in those with additional risk factors
when 10 year cardiovascular disease risk estimated from conventional risk factors is
15% or more. However clinical judgement is required, particularly when there are
multiple additional risk factors.
Communication and negotiation with people to explain and agree a management
plan, and encourage concordance is important.
Consider simvastatin 40 mg od if 10 year CVD risk ≥ 20%, or ≥ 15% with
additional risk factors (use clinical judgement, discussion with patient)
The NICE lipid modification guideline recommends simvastatin 40 mg od as first line.
If simvastatin 40 mg od is not tolerated, a lower dose may be considered, or an
alternative statin, with similar acquisition costs, such as pravastatin. In all people
secondary causes should be excluded, and the NICE lipid modification recommends
a fasting lipid profile is measured before a statin is initiated.
17
3 month lipid profile to assess concordance, not for dose titration, then
annual review
The NICE lipid modification guideline does not recommend that the lipid profile is
monitored in people treated for primary prevention. However, there was a consensus
to recommend this for FATS5, with the rationale that high risk people being treated
for primary prevention with drug treatment will require review, and the purpose of
monitoring is to review the response to treatment. If the fall in cholesterol is < 1
mmol/l, concordance both with drug treatment and with diet should be reviewed, as
well as ensuring secondary causes have been excluded. However, routine titration of
statins is not recommended in this group of people, consistent with the NICE lipid
modification guideline.
All people being treated with drugs for primary prevention should have an annual
review.
If metabolic syndrome or impaired fasting glycaemia; ensure
intensive therapeutic lifestyle interventions (see supporting notes)
People with a combination of factors which increase the future risk of cardiovascular
disease and diabetes may be diagnosed as having the metabolic syndrome. The
metabolic syndrome is diagnosed when 3 or more of the following are present;





Excess body fat, particularly abdominal fat – ‘central obesity’.;
BMI ≥ 30, or
BMI < 30 with increased waist circumference (Caucasian men ≥ 102 cm (40 in),
women ≥ 88 cm (35 in), Asian men ≥ 90 cm (35 in), women ≥ 80 cm (32 in))
Raised fasting triglycerides > 1.7 mmol/l
Low HDL cholesterol < 1.0 mmol/l in men and < 1.2 mmol/l in women
Blood pressure ≥ 130/85 mmHg (using the large cuff if appropriate), or treated
hypertension
Impaired fasting glycaemia (see local diabetes guidelines), or diagnosed diabetes
or IGT
Lifestyle interventions are recommended for all people treated for cardiovascular
prevention, as part of an overall management plan, but in FATS5, as in FATS4, the
particular importance of therapeutic lifestyle interventions in those with the metabolic
syndrome, and impaired fasting glycaemia, as well as in those with diabetes and IGT,
is emphasised.
Vascular risk factors in people with the metabolic syndrome and impaired fasting
glycaemia are usually particularly responsive to intensive therapeutic lifestyle
changes which include;



Reduced intake of total and saturated fat
Increased physical activity
Weight reduction
18
Thus, intensive therapeutic lifestyle changes are particularly emphasised, with
cardiovascular risk assessed annually. Any hypertension should be appropriately
managed and lipid lowering drugs offered as appropriate, based on an overall
cardiovascular risk assessment.
19
ADDITIONAL NOTES (SEE FULL SUPPORTING NOTES FOR MORE
INFORMATION):
Consider familial hypercholesterolaemia (FH) if total cholesterol > 7.5
mmol/l, LDL cholesterol > 4.9 mol/l. Suspected FH or if triglycerides > 4.5
mmol/l, treat individually, consider discussion with local advisor - see
supporting notes
These thresholds are included as people with very high total cholesterol and/or
triglycerides may require different drug therapies to those routinely recommended in
FATS5, and some may have familial conditions and also require family screening. It
is recommended that the Simon Broome criteria are used for a clinical diagnosis of
familial hypercholesterolaemia (FH) (see NICE guideline CG071 for details). In brief
that is in adults;
Definite FH
Total cholesterol > 7.5 mmol/l (either pre-treatment or highest on treatment) in adults
over 16 years, or LDL cholesterol > 4.9 mmol/l
plus
Either tendon xanthomata in the person or 1st or 2nd degree relative and/or DNAbased evidence of an LDL receptor mutation or familial defective apoB-100.
Possible FH
Total cholesterol > 7.5 mmol/l (either pre-treatment or highest on treatment) in adults
over 16 years, or LDL cholesterol > 4.9 mmol/l
plus one of the following
Family history of myocardial infarction before age 50 years in 2nd degree relative or
before 60 years in 1st degree relative
Family history of raised total cholesterol > 7.5 mmol/l in 1st or 2nd degree relative.
People with definite or possible FH should be considered for referral to the lipid clinic
for confirmation of the diagnosis and initiation of family cascade testing, where
appropriate.
High triglycerides
People with high triglycerides require individual assessment and management.
Those with triglycerides above 10 mmol/l are at risk of acute pancreatitis and
specialist advice should be obtained urgently. In others, intensive therapeutic lifestyle
changes should be recommended (diet, alcohol, physical activity), and some will
require specialist referral. See above for management of people with Type 2
diabetes.
Local advisors
These can be contacted by email;
Dr Neely in Newcastle upon Tyne Hospitals NHS Foundation Trust
([email protected])
Dr McKenna in Northumbria Healthcare NHS Foundation Trust
([email protected])
20
Consider secondary causes of hyperlipidaemia – alcohol / thyroid / diabetes /
nephrotic syndrome / liver disease / drug induced
This is consistent with previous iterations of FATS. All people with hyperlipidaemia
being considered for lipid lowering drug treatment should have secondary causes of
dyslipidaemia excluded. The table below describes some of the causes of secondary
dyslipidaemia.
Secondary causes of dyslipidaemias
Condition / drug
treatment
Lipid change
Cholesterol
Diabetes mellitus
Untreated
hypothyroidism
Alcohol excess
Obesity
Chronic renal failure
Nephrotic syndrome
Cholestasis
Gout
Pregnancy
Anorexia nervosa
Hypopituitarism
Long term drug
treatment
Anticonvulsants
Androgens
Atypical
antipsychotics
Beta blockers
Corticosteroids
Ciclosporin
HIV/anti-retroviral
drugs
Oral oestrogens
Retinoids
Triglycerides
++/+
Lipoprotein
elevated
HDL
cholesterol
-
++
++/+
-
VLDL
VLDL
VLDL/ LDL
VLDL/ LDL
LDL
VLDL
VLDL
LDL
VLDL/ LDL/ IDL
+/+++
+/+++
+/++
-/--
HDL
Lowers HDL
VLDL/LDL
+
+
+
+
+
+/++
-
VLDL
VLDL/ LDL
LDL/ VLDL
VLDL
+
++/+
+
-
VLDL
VLDL
+
++
++
+/+
+/+++
++/+
+
++
+
+
-
VLDL
LDL
+
+/++
Initiate with a lower dose if at increased risk of adverse side effects or if treated
with other drugs which may interact (eg verapamil, diltiazem, amiodarone,
fibrates, ciclosporin. Temporarily stop simvastatin if treated with erythromycin,
clarithromycin, some anti-fungals. ) See supporting notes/BNF
No revision has been made about this for FATS5. Some people may be at increased
risk of adverse side effects with higher doses of simvastatin and it is recommended
21
that lower doses of simvastatin be considered in such people, and simvastatin 80 mg
is only recommended after careful consideration of the risks and benefits (see
above).

CKD with eGFR ≤ 30 ml/min/1.73m2 (initial dose of simvastatin 10 mg od, higher
doses with caution)
 Older people particularly those who are frail and or have a low muscle mass
 Untreated muscle disorder, or other conditions which may be associated with
‘vulnerable’ muscles eg PMR (CK measurement recommended at baseline in these
groups, but not in all people)
 Untreated hypothyroidism (until corrected)
 Alcohol abuse
Grapefruit juice should be avoided, as it interferes with simvastatin metabolism.
All statins and fibrates are contra-indicated in pregnancy.
A number of other drugs interact with simvastatin and dosage modifications may be
required. Information is available in the BNF. Examples are included in the table
below (the list is not exhaustive, but includes some of the commoner drugs used, and
the BNF should be referred to);
Drug
Amiodarone
Anti-fungal agents
(ketocoanzole, itraconazole,
miconazole, posaconazole)
Ciclosporin
Danazol
Diltiazem
Erythromycin / clarithromycin /
telithromycin
Fibrates
Gemfibrozil
HIV protease inhibitors
Nicotinic acid
Verapamil
Recommended doses of simvastatin
Maximum simvastatin 20 mg od
Avoid concomitant use, temporarily discontinue simvastatin
during treatment with anti-fungal agents
Maximum simvastatin 10 mg od
Maximum simvastatin 10 mg od
Maximum simvastatin 40 mg od
Avoid concomitant use. Temporarily discontinue simvastatin
during treatment with erythromycin, clarithromycin or
telithromycin
Combination treatment generally following recommendation
from specialist care only. Increased risk of myopathy
Avoid concomitant use
Avoid concomitant use. Consider alternative statin. Refer to
BNF
Combination treatment generally following recommendation
from specialist care only. Increased risk of myopathy.
Maximum dose of simvastatin 10 mg od
Maximum simvastatin 20 mg od
Simvastatin/fibrate potentiates warfarin – initiate 3 - 5 days before INR
check
The interaction between simvastatin and warfarin has been addressed in previous
iterations of FATS. Simvastatin modestly potentiates warfarin, but can still be used in
combination. Fenofibrate also potentiates warfarin. People should be advised to start
or up-titrate simvastatin or fenofibrate 3 to 5 days before the date of the next INR and
a note made in the ‘yellow book’ that the drug has been started or dose changed.
22
Clinical judgement should be used to decide if an adjustment in the warfarin dose is
required prior to starting treatment, particularly when starting fenofibrate.
Review concordance and lifestyle if initial cholesterol or non HDL
cholesterol falls < 1 mmol/l
It is anticipated that in the majority of people treated with simvastatin 40 mg daily or
higher intensity statin, total cholesterol and non HDL cholesterol will fall by at least 1
mmol/l from baseline, and usually more. Evidence from the Heart Protection Study is
that the average cholesterol lowering during the trial with simvastatin 40 mg daily
was about 1.8 mmol/l In a summary estimate from 164 trials reported in the full
version of the lipid modification guideline, the average fall in total cholesterol was
2.14 mmol/l. If cholesterol fails to fall, it is recommended that the notes are reviewed
to ensure secondary causes have been excluded and concordance is reviewed with
the patient. In people being considered for further increments in the drug flow
concordance with medication and lifestyle should be considered at each step.
Treatment in older people; see supporting notes
This was discussed for FATS4 and is maintained for FATS5. The following was
noted;
 Life expectancy in people of different ages (this included all people, not just those
who are well) was reviewed. At the age of 80 years, the average life expectancy in
men is about 7 years and in women 9 years. At the age of 90 years, the average
life expectancy in both men and women is about 4 years
 People who are older are more likely to have a circulatory death than those who
are younger. If statins are of benefit, that benefit may be greater in an older person
than a younger
 Correcting for frailty, co-morbidity and first year events, cholesterol is a risk factor
in older people
 The statin trials show no trend in difference in efficacy of statin treatment with
older age
People with occlusive vascular disease and diabetes / IGT should be offered
treatment irrespective of age. For those without known vascular disease or diabetes,
the cardiovascular risk assessment tools are not validated and the recommendation
in the NICE lipid modification guideline is appropriate. People aged 75 years and
over should be considered to be at increased risk, particularly those who smoke and
or have hypertension. People should be assessed for the benefits and risks of
treatment, including considering any co-morbidities and the preferences of the
patient, when deciding about treatment.
Older people have a higher risk of drug side effects and a lower initial dose of
simvastatin may be preferred in this group.
23
APPENDIX
Membership of the FATS steering group
Dr Jane Skinner, Consultant Community Cardiologist, Newcastle upon Tyne
Hospitals NHS Foundation Trust (guideline co-ordinator)
Dr Phil Adams, Consultant Cardiologist, Newcastle upon Tyne Hospitals NHS
Foundation Trust
Dr Stuart Bennett, Consultant in Diabetes, Northumbria Healthcare NHS Foundation
Trust
Dr Sibal Bharat, Consultant in Public Health Medicine, North Tyneside PCT
Dr Steve Blair, GP, Village Green Surgery
Dr John Bourke, Consultant Cardiologist, Newcastle upon Tyne Hospitals NHS
Foundation Trust
Dr Andrew Chalmers, GP, Beaumont Park, Whitley Bay
Dr Richard Curless, Northumbria Healthcare Trust
Dr J Colin Doig, Consultant Cardiologist, Northumbria Healthcare NHS Foundation
Trust
Tim Donaldson, Medicines Management Lead, Northumberland Tyne and Wear NHS
Trust
Christine Dryden, Community Cardiology, North Tyneside PCT
Dr Sharon Gandy, GP, North Shields
Dr Akif Gani, Consultant in Elderly Care, Newcastle PCT
Dr Ifit Haq, Consultant Cardiologist, Newcastle upon Tyne Hospitals NHS Foundation
Trust
Dr Gillian Hawthorne, Consultant Community Diabetologist, Newcastle PCT
Prof Philip Home, Consultant in Diabetes, Newcastle upon Tyne Hospitals NHS
Foundation Trust
Zahra Irranejad, Pharmaceutical Advisor, Newcastle PCT
Dr Suren Kanagasundaram, Consultant in Renal Medicine, Newcastle upon Tyne
Hospitals NHS Foundation Trust
Margaret King, Programme Co-ordinator, Community Cardiac Care, Newcastle PCT
Dr Nick Lewis-Barned, Consultant in Diabetes, Northumbria Healthcare NHS
Foundation Trust
Dr Paul Mackin, Consultant Psychiatrist, Northumberland Tyne and Wear NHS Trust
Dr Paul McKenna, Consultant Chemical Pathologist, Northumbria Healthcare NHS
Foundation Trust
Dr Dermot Neely, Consultant in Clinical Biochemistry and Metabolic Medicine,
Newcastle upon Tyne Hospitals NHS Foundation Trust
Dr Wan-Fai Ng, Consultant Rheumatologist, Newcastle upon Tyne Hospitals NHS
Foundation Trust
Dr Matthew Pettifer, GP, Northumberland
Dr Mike Scott, GP, Newburn Surgery, Newcastle
Dr Caroline Sprake, GP, North Tyneside
Prof Gerry Stansby, Consultant Vascular Surgeon, Newcastle upon Tyne Hospitals
NHS Foundation Trust
Deb Stone, Dietician, Healthy Hearts, Northumbria Healthcare NHS Foundation Trust
Dr Simon Thomas, Consultant Physician, Newcastle upon Tyne Hospitals NHS
Foundation Trust
Mr Glyn Trueman, Formulary Pharmacist, Newcastle upon Tyne Hospitals NHS
Foundation Trust
24
Susan Turner, Pharmaceutical Advisor (commissioning), NHS North of Tyne
Dr John Waddell, GP, Northumberland
Dr Mark Walker, Consultant Physician, Newcastle upon Tyne Hospitals NHS
Foundation Trust
Rachael Wiedmann, Pharmacist, Northumbria Healthcare NHS Foundation Trust
Dr Azfar Zaman, Consultant Cardiologist, Newcastle upon Tyne Hospitals NHS
Foundation Trust
Declared conflicts of interest
JSS has received travel grants and honoraria from various pharmaceutical
companies that manufacture lipid lowering drugs. PCA has received support from
drug companies involved in statin and ezetimibe trials and promotion for research,
travel and received honoraria for speaking. CD has received funding support for
training from various pharmaceutical companies that manufacture lipid lowering
drugs. JCD has received honoraria from various pharmaceutical companies which
manufacture lipid lowering drugs and has participated in advisory boards for Merck
and Astra-Zenica. IUH has received travel grants and honoraria from various
pharmaceutical companies that manufacture lipid lowering drugs, and is an
investigator for sponsored trials which include simvastatin and ezetimibe. PH has
declared non-personal, non-specific duality of interests as various manufacturers of
blood lipid modifying drugs support educational and research activities of his
University, Trust, the International Diabetes Federation, the Worldwide Initiative for
Diabetes Education in regard of diabetes products and activities, and was the clinical
advisor for the NICE guidelines for management of Type 2 diabetes. NL-B has
participated in an independent advisory board meeting for Astra-Zeneca. ST was an
ASCOT investigator (Pfizer) and has received travel grants and honoraria from
various pharmaceutical companies that manufacture lipid lowering drugs. PM was an
investigator in the HPS and SEARCH trials, and is an investigator for HPS2-THRIVE
trial organised by the CTSU, Oxford, and has received travel grants from various
pharmaceutical companies that market lipid lowering drugs. RGDN is chair of Heart
UK and has received travel grants and honoraria from various pharmaceutical
companies that manufacture lipid lowering drugs and has participated in advisory
boards for MSD-Schering Plough and Pfizer. MS has received honoraria for
speaking and educational grants from various pharmaceutical companies, and works
for Mediproof which is funded by pharmaceutical companies. GS has received
honoraria from various pharmaceutical companies for speaking and chairing
meetings
Date of review
February 2012, or earlier if required by new evidence.
25
FATS5 : 2009

This is a lipid lowering drug strategy which should only be used
within an overall lifestyle and clinical management strategy
 It is assumed that people with contraindications will be identified
and excluded (refer to the BNF).
 This summary should be used with the supporting documentation
People with symptomatic or prior occlusive vascular disease
 Measure lipid profile (total cholesterol, HDL cholesterol, triglycerides)
 Measure ALT or AST at baseline (and after 3 months if high dose statin)

If ALT or AST < 2 fold normal, prescribe a statin as below
 In acute coronary syndrome/ acute MI ; Atorvastatin 80 mg od
 In all others; Initiate simvastatin 40 mg od
Consider titration to simvastatin 80 mg od (benefits/risks)

Repeat lipid profile 8 weekly until TC < 4 mmol/l, or LDL-C (fasting) <
2 mmol/l, or non-HDL-C < 2.8 mmol/l or maximum drug flow reached
(see supporting notes)

People intolerant of recommended statin; see supporting notes
 Higher risk people ie diabetes, disease in > 1 arterial bed (CHD,
cerebrovascular, PAD), after CABG and recurrent spontaneous acute CVD
events within a year, consider titration to atorvastatin 80 mg od /
simvastatin 40 mg plus ezetimibe 10 mg od; see supporting notes.
People with Type 1, Type 2 diabetes, or IGT (OGTT)
Consider drug treatment in people with;
 Type 1 and Type 2 diabetes with microalbuminuria/proteinuria
 Type 1 diabetes / Type 2 diabetes / IGT aged ≥ 40 years
 Type 1 diabetes / Type 2 diabetes / IGT aged < 40 years if other
cardiovascular risk factors present using clinical judgement
 Drug flow;
Simvastatin 40 mg od
Consider simvastatin 80 mg od (benefits/risks)
Atorvastatin 80 mg od / simvastatin 40 mg plus
ezetimibe 10 mg od only if established CVD
 Threshold for titration and additional notes; see other sections
 Type 2 diabetes and triglycerides > 1.7 mmol/l < 10 mmol/l; therapeutic
lifestyle measures for 6 months, then consider adding a fibrate (see
supporting notes)
February 2009
PTO
High risk people without symptomatic or prior occlusive vascular disease
and without diabetes / IGT (OGTT)
FATS advice is based on risk not cholesterol, discuss risk not just cholesterol
In people at high risk of developing vascular disease
 Measure total and HDL cholesterol, triglycerides (non-fasting acceptable)
 Estimate 10 year CVD risk (Framingham)
 If definite LVH on ECG, double 10 year CVD risk (if not already included)
 Consider other additional risk factors:
Family history of premature CHD (men< 55 yrs, women< 65 yrs)
South Asian origin
Fasting triglycerides > 1.7 mmol/l
High level of deprivation
Premature female menopause aged ≤ 45 years
Other conditions (eg CKD, inflammatory arthritis, connective tissue
disease, severe mental illness, other severe inflammatory conditions)
 Consider simvastatin 40 mg od if 10 year CVD risk ≥ 20%, or ≥ 15% with
additional risk factors (use clinical judgement, discussion with patient)
 3 month lipid profile to assess concordance, not for dose titration, then
annual review
 If metabolic syndrome or impaired fasting glycaemia; ensure intensive
therapeutic lifestyle interventions (see supporting notes)
Additional notes (see full supporting notes for more information):
1. Consider familial hypercholesterolaemia (FH) if total cholesterol > 7.5
mmol/l, LDL cholesterol > 4.9 mol/l. Suspected FH or if triglycerides > 4.5
mmol/l, treat individually, consider discussion with local advisor.
2. Consider secondary causes of hyperlipidaemia – alcohol / thyroid / diabetes /
nephrotic syndrome / liver disease / drug induced
3. Initiate with a lower dose if increased risk of adverse side effects or treated
with other drugs which may interact (eg verapamil, diltiazem, amiodarone,
fibrates, ciclosporin). Temporarily stop simvastatin if treated with
erythromycin, clarithromycin, some anti-fungals (supporting notes/BNF)
4. Simvastatin/fibrate potentiate warfarin – initiate 3 - 5 days before INR check
5. Review concordance and lifestyle if initial total cholesterol and non HDL
cholesterol falls < 1 mmol/l
6. Treatment in older people; see supporting notes
FATS5 developed in the light of new evidence and monitoring of FATS1,2, 3 & 4
Agreed with Primary and Secondary Care Users North of Tyne
February 2009
February 2009
PTO
February 2009