Update'on'NICE'Lipid'Guidelines'
Dr'Jim'Moore''
GP'and'GPSI''
Pathological*process**
LDL-C: Lower is better
Summary of key outcomes trials
Adapted from Rosenson R. Exp Opin Emerg Drugs (2004); LaRosa J. NEJM (2005); and Calhoun H. Lancet (2004)
Lipid'modifica=on:'cardiovascular'risk'
assessment'and'the'modifica=on'of'
blood'lipids'for'the'primary'and'
secondary'preven=on'of'
cardiovascular'disease'
Iden=fying'and'assessing'CVD'risk'
Primary prevention
Identifying people for a full formal risk assessment
Use a systematic strategy to identify those likely
to be at high risk of CVD
•  estimate CVD risk and prioritise those with a
10 year CVD risk of 10% or more for a full
formal risk assessment
•  Review risk in over 40’s on an ongoing basis
Do not use opportunistic assessment as the
main strategy to identify CVD in unselected
people
Primary Prevention
Full formal risk assessment
Use QRISK 2 risk calculator
•  Up to 84 years old
•  In Type 2 Diabetes
•  Consider other factors not included in formal risk score
Do not risk assess
•  Existing CVD or familial lipid disorder
•  Type 1 diabetes
•  CKD(3 or more)
•  85years or older…assume they have CVD
Discuss absolute risk of CVD including benefits and harms of
treatment over a 10 year period.
QRISK®2-2014 risk calculator: http://qrisk.org
NICE
JBS3
Lipid'measurement'and'referral''
•  Ini=ally'measure'total'cholesterol'
(TC)and'HDL'
'
•  Before'star=ng'lipid'modifica=on'
therapy'measure'extended'lipid'
profile'to'include'TC,'HDL,'Non'HDL'
and'Triglycerides(TG)'(…and'LDL?)'
'
•  Refer'to'lipid'specialist'if'the'clinical'
findings,'lipid'profile'(Simon'Broome'
Criteria)'and'family'history'suggest'a'
likely'inherited'cause'
HDL''Q'LDL'Q'NonQHDL'cholesterol'
•  High Density (Highly desirable) Lipoprotein or HDL
- is inversely related to CHD risk….the higher the better!
- average HDL value in the UK is 1.2 for men and 1.4 for
women.
- TC/HDL ratio greater predictive value for CHD than LDL .
•  Low Density (Less desirable) Lipoprotein
- is directly related to CHD risk….the lower the better
- 1 mmol reduction in LDL =22% reduction in CVD events
•  Non HDL cholesterol
- easier to measure and will be adopted in future research
- is directly related to CHD risk….the lower the better
- calculated by subtracting HDL from the total cholesterol
- has a greater predictive value for CHD than LDL
- is a surrogate for Apolipoprotein B
- non HDL =1.24 x LDL
- 1mmol reduction in HDL = 18% reduction in CVD events
Lipid profiles
The BIGGER picture
•  Patient A - Tot Chol 5.5 : HDL 2.4, LDL 2.6, Non-HDL 3.1 ,
TG 1.9, TC/HDL 2.3
•  Patient B - Tot Chol 5.5 : HDL 0.7, LDL 4.0, Non-HDL 3.8,
TG 4.9, TC/HDL 7.8 …the metabolic syndrome !
•  95% confidence limits on a single cholesterol measurement
are around ± 14% of the true value
Lifestyle'modifica=on'for'primary'and'
secondary'preven=on'of'CVD''
Cardioprotec+ve-diet-
''Advise*people*at*high*risk*of*or*with*CVD*to*eat*a*diet*in*which**
•  total'fat'intake'is'30%'or'less'of'total'energy'intake'
•  saturated'fats'are'7%'or'less'of'total'energy'intake'
•  intake'of'dietary'cholesterol'is'less'than'300'mg/day'
•  where'possible'saturated'fats'are'replaced'by'mono unsaturated'and'
polyunsaturated'fats.'.''
•  replace'their'saturated'and'mono unsaturated'fat'intake'with'olive'oil,'
rapeseed'oil'or'spreads'based'on'these'oils.'.''
•  Choose'wholegrain'varie=es'of'starchy'food''
•  Reduce'their'intake'of'sugar'and'food'products'containing'refined'
sugars''
''''Eat*at*least*….*
•  5'por=ons'of'fruit'and'vegetables'per'day''
•  2'por=ons'of'fish'per'week,'including'a'por=on'of'oily'fish'
•  4'to'5'por=ons'of'unsalted'nuts,'seeds'and'legumes'per'week.'
Physical'ac=vity'
Advise'people'at'high'risk'of'or'with'CVD'to'do'the'following'every'week:''
•''''at'least'150'minutes'of'moderate'intensity'aerobic'ac=vity''
''''''or''
•'''75'minutes'of'vigorous'intensity'aerobic'ac=vity'
''''''or''
•'''''a'mix'of'moderate'and'vigorous'aerobic'ac=vity'in'line'with'na=onal'guidance''''
for'the'general'popula=on'
'
•  Advise'people'to'do'muscleQstrengthening'ac=vi=es'on'2'or'more'days'a'week'
that'work'all'major'muscle'groups'(legs,'hips,'back,'abdomen,'chest,'shoulders'
and'arms)'in'line'with'na=onal'guidance'for'the'general'popula=on''
'
•  Encourage'people'who'are'unable'to'perform'moderateQintensity'physical'
ac=vity'because'of'comorbidity,'medical'condi=ons'or'personal'circumstances'
to'exercise'at'their'maximum'safe'capacity.'[2008,'amended'2014]''
Lifestyle…con=nued'
'''Weight*management*
•  Offer'people'at'high'risk'of'or'with'CVD'who'are'overweight'or'obese'
appropriate'advice'and'support'to'work'towards'achieving'and'
maintaining'a'healthy'weight'
''''Alcohol*
•  Be'aware'that'men'should'not'regularly'drink'more'than'3–4'units'a'
day'and'women'should'not'regularly'drink'more'than'2–3'units'a'day.''
''''''Smoking*cessa?on*
•  Offer'people'who'want'to'stop'smoking'support'and'advice,'and'
referral'to'an'intensive'support'service'(for'example,'the'NHS'Stop'
Smoking'Services).'[2008]'
•  If'a'person'is'unable'or'unwilling'to'accept'a'referral'to'an'intensive'
support'service,'offer'them'pharmacotherapy'in'line'with'smoking'
cessa=on'services'
'''''Plant*stanols*and*sterols**
•  no'longer'recommended'
Lipid'modifica=on'for'primary'and'
secondary'preven=on'of'CVD''
Lipid modification therapy
•  Use evidence based therapies that reduce
CVD morbidity and mortality
•  Statins lower LDL
•  If using statins then choose one of high
intensity and low acquisition cost
On-Treatment LDL and CHD
Events in Statin Trials
30'
4S'Q'PBO'
Event'rate'(%)'
*Secondary*Preven?on*
4S'Q'Rx'
20'
LIPID'Q'PBO'
CARE'Q'PBO'
LIPID'Q'Rx'
10'
TNT'Q'ATV10'
PROVEQIT'Q'PRA'
TNT'Q'ATV80'
PROVEQIT'Q'ATV80'
0'
HPS'Q'PBO'
CARE'Q'Rx'
HPS'Q'Rx'
WOSCOPS'Q'PBO'
AFCAPS'Q'PBO'
AFCAPS'Q'Rx'
WOSCOPS'Q'Rx'
ASCOT'Q'PBO'
ASCOT'Q'Rx'
40'
(1.0)'
60' 70' 80'
(1.6)' (1.8)' (2.1)'
100'
(2.6)'
Primary Prevention
120'
(3.1)'
140'
(3.6)'
LDLQC'achieved,'mg/dL'(mmol/L)'
Adapted from Rosenson RS. Expert Opin Emerg Drugs. 2004;9:269-279.
LaRosa JC et al. N Engl J Med. 2005;352:1425-1435.
160'
(4.1)'
180'
(4.7)'
200'
(5.2)'
NonQadherence'can'lead'to'poor'cholesterol'
management'thereby'increasing'CV'risk'
• 
• 
Even'mild'sta=nQrelated'muscle'ache'may'diminish'pa=ent’s'quality'of'life'“…mild'
MRAEs'[muscleQrelated'adverse'events]'of'sta=ns'can'reduce'quality'of'life,'reduce'
treatment'adherence,'and'impair'cardiovascular'outcome1'
Rises'in'TC'1mmol/L'increases'the'risk'of'coronary'events'up'to'72%2'
1.  Jacobson'TA.'Mayo%Clinic%Proc%2008;'83:'687–700.'
2.  NICE'clinical'guideline'67'for'lipid'modifica=on.'Available'at:'www.nice.org.uk'Last'accessed''November'2014'
3.  Baigent'C,'et'al.'Lancet%2005;'366:1267–1278.'
•  Choose statin of high intensity and low acquisition cost
Primary prevention
Offer atorvastatin 20mg to
•  Up to age 84 years with 10% or greater risk of CVD over 10 years
•  CKD
•  Type 1 Diabetes
- over 40 years old
- for 10 years or not
-concomitant nephropathy or CVD risk factors
Consider atorvastatin 20mg
•  all adults with Type 1 Diabetes
•  over 85 years old
GDG on…..”Why atorvastatin 20mg”
•  QALY £4125
•  “most clinically and cost effective option for Primary Prevention”
Vascular*deaths*avoided*per*100*
Major*vascular*events*avoided*per*100*
Sta=n'therapy'has'proven'benefit'even'in'lowQrisk'
individuals'with'established'hypercholesterolaemia1'
Benefit'in'lowQrisk'individuals*'exceeds'known'hazards'of'sta=n'therapy.'
These'individuals'not'typically'regarded'as'suitable'for'sta=n'therapy'in'
current'guidelines'1.'Kotseva'K,'et'al.'Eur%J%Cardiovasc%Prev%Rehabil%2010;'17:'530–540.'
Primary*Preven?on*
Cochrane*review*sta?ns*vs*placebo*or*control*group*
18RCTs'
CVD'risk'15%'in'10years''
Overall'adverse'events'17%'in'both'groups'
Treatment'stopped'in'12%of'pa=ents'in'both'groups'
Incidence'of'myalgia,'rhabdomyolysis,'liver'enzyme'abnormali=es'and'renal'
dysfunc=on'similar'in'both'groups'
Authors'concluded'that'….“The*benefits*of*sta?ns*outweigh*the*risk*of*serious*
life*threatening*illness”*
• 
• 
• 
• 
• 
Secondary prevention
Start atorvastatin 80mg (unlicenced) daily
•  established CVD
•  established CVD and CKD
•  Without delay in ACS
…use lower dose of atorvastatin if
- potential drug interactions
- high risk of side effects
- patient preference
GDG on ..Why Atorvastatin 80mg?
•  QALY £4875
•  High intensity statins are cost effective as a group in
Secondary prevention
•  Simvastatin 80mg cost effectiveness /side effect profile
Serum'Triglycerides''
In*people*with*a*triglyceride*concentra?on*between*10*and*20*mmol/litre:*
•  repeat'the'triglyceride'measurement'with'a'fas=ng'test'(aper'an'interval'of'
5'days,'but'within'2'weeks)''
'''**and*
•  review'for'poten=al'secondary'causes'of'hyperlipidaemia''
''***and*
•  seek'specialist'advice'if'the'triglyceride'concentra=on'remains'above'10'mmol/
litre.'[new'2014]'
*
In*people*with*a*triglyceride*concentra?on*between*4.5*and*9.9*mmol/litre*
•  be'aware'that'the'CVD'risk'may'be'underes=mated'by'risk'assessment'tools'and*
•  op=mise'the'management'of'other'CVD'risk'factors'present''
''***and*
•  seek'specialist'advice'if'non HDL'cholesterol'concentra=on'is'more'than'7.5'
mmol/litre.'[new'2014]'
Do not offer as monotherapy or in
combination with statins….
• 
• 
• 
• 
Fibrates (routinely)
Nicotinic acid
Bile acid sequestrants
Omega 3 Fatty acid compounds
….this includes patients with
-CKD
-Type 1 Diabetes
-Type 2 Diabetes
For Ezetimibe follow NICE ( TA 132 )guidance( use statin
where possible)
Follow up & targets
in Primary and Secondary prevention
•  Measure TC, HDL and non-HDL at 3 months
•  Aim for a greater than 40% reduction in
non-HDL cholesterol
•  Annual reviews for all patients thereafter
If not achieved
•  optimise lifestyle measures(if not already achieved)
•  Consider titrating dose of atorvastatin to 80mg where not
already taking
•  Discuss with patients (at medication review) on low/medium
intensity statins the benefits/risks of high intensity statins
Advice and monitoring
Liver transaminases
•  Check ALT /AST at baseline, 3 months and one year of
statin therapy and not routinely thereafter
•  Do not withdraw if ALT/AST increases up to x3 ULN
Creatine Kinase
•  Measure pre statin if generalised muscle aches only
-if persistenly raised x5 ULN withold statin
-if raised but less than x5 ULN then start statin at lower
dose
If patients develop significant muscle symptoms taking statin
then measure CK
Muscle related side effects
•  Myalgia -
normal CK
190:100,000 patient years
•  Myopathy
>10x ULN CK
5:100,000 patient years
•  Rhabdomyolysis
>40x ULN CK
or ! CK+AKI
1.6:100,000 patient years
Clinical evidence
•  No clinical difference in incidence of myalgia in statin Rx vs
placebo groups up to 6 years
•  Medium intensity statin showed less myalgia cf high intensity
statin up to 5 years
•  In HPS 33% patients in simvastatin and placebo groups
reported muscle pain at some time in study
Factors'that'increase'risk'of'muscle'ache'with'sta=n'
use1'
Patient properties
Statin properties
• 
• 
• 
• 
• 
• 
• 
•  High dose
•  Potential for drug-drug
interactions (CYP3A4*)
•  Lipophilicity
•  High bioavailability
•  Limited protein binding
Increasing age
Female
Renal insufficiency
Hepatic dysfunction
Hypothyroidism
Diet (grapefruit juice)
Polypharmacy
'
Increased statin serum concentration
Increased potential for muscle ache
*CYP:'cytochrome'P450'
1.  Adapted'from'Rosenson'RS.'Am%J%Med'2004;'116:'408–416.'
Intolerance of statins
Not tolerating high intensity statin then consider
• 
• 
• 
• 
• 
Stopping statin till symptoms resolved (if at all) and then restart
Reduce dose of statin within same intensity group
Change to a statin of lower intensity group
Do not offer coenzyme Q10 or Vitamin D
Seek specialist advice if intolerant of three statins
……. any statin at any dose reduces CVD risk
The'sta=nQassociated'risk'of'developing'diabetes'is'low'in'
absolute'terms'when'compared'with'the'reduc=on'in'coronary'
events1'
• 
• 
• 
• 
Results'of'a'metaQanalysis'of'13'trials'show'that'sta=ns,'as'a'class,'slightly'increase'
the'risk'of'diabetes1'
In'preQdiabe=c'pa=ents'(FPG'5.6–6.9'mmol/L),'rosuvasta=n'has'been'associated'
with'an'increased'risk'of'diabetes2'
Addi=onal'factors'hypertension,'!'Triglycerides,'!BMI'
The'risk,'however,'is'outweighed'by'the'reduc=on'in'vascular'risk'with'sta=ns'and'
therefore'should'not'be'a'reason'for'stopping'sta=n'treatment1Q3'
NNH:'number'needed'to'harm''–''
1'addi=onal'case'of'diabetes'for'every'
498'pa=ents'treated'per'year4'
'
NNT:'number'needed'to'treat''–''
155'pa=ents'treated'with'a'sta=n'to'
prevent'1'CV'event'per'year4'
New*onset*diabetes*
NNH:*498*
Cardiovascular*events*
NNT:*155*
1. 
2. 
3. 
4. 
Sasar'N,'et'al.%Lancet%2010;'375:'735–742.'
CRESTOR.'Summary'of'Product'Characteris=cs.'Nov'2014.'
Ridker'PM'et'al.%NEJM'2008;'359:'2195–2207'
Lipitor.'Summary'of'Product'Characteris=cs.'Nov'2014'
Preiss'D,'et'al.'JAMA.'2011;'305:'2556–2564.''
Figure'adapted'from'Preiss'D,'et'al.'20114''
Musings''
'''''''''''''''''''''''''*********NICE*vs*JBS*3*
'
'''''''''''''''''''''''''''''''''NICE''''''''''''''''''''''''''''''''JBS3'
•  Sta=n''''''''''Atorvasta=n20/80mg''''Atorvasta=n'
•  Lipid'targets''''>'40%'"'Non'HDL'''''LDL<1.8,NonHDL<2.5'
•  ''T2'Diabetes''''(risk'assess)''''''''''''''''''''High'risk''
Thank you
…….any questions ?