This document provides guidelines for the assessment and management of dyslipidemia from several major organizations. It discusses risk assessment tools for cardiovascular disease from ATP III, ADA, ACC/AHA, and QRISK2. It also compares statin intensity categories between NICE and ACC/AHA guidelines. The document recommends lifestyle modification as first-line treatment and the use of high-intensity statins for primary and secondary prevention of CVD according to the guidelines of NICE, ADA, and ACC/AHA.

1. DYSLIPIDEMIA
CLINICAL GUIDELINES UPDATE
DR. MOHAMMAD DAOUD
CONSULTANT ENDOCRINOLOGIST
KAMC-NGHA JEDDAH

2. THE AGENDA…
INTRODUCTION
RISK ASSESSMENT TOOLS
GUIDELINES : HEAD TO HEAD
MANAGEMENT : STATINS +/-
CONCLUSION

3. CARDIOVASCULAR DISEASE (CVD)
 (CVD) = Disease of the heart and blood vessels
caused by the process of atherosclerosis;
Includes CHD; ACS/Angina, TIA/Stroke and PAD
 The leading cause of death in many countries
with significant cost implications
 Though mortality from CVD is falling but
morbidity appears to be rising

4. CARDIOVASCULAR DISEASE (CVD)
(CVD) predominantly affects people older than 50 years
Risk factors
Non-modifiable
Age
Sex
Family history of CVD
Ethnic background
Modifiable
Smoking
HTN
Dyslipidemia
DM
Social : Low income
and social deprivation

5. WHERE WE ARE WE NOW?
FROM ….TO

6. Risk stratification based on Five major steps.
- Obtain Fasting Lipid profile
- Identify CHD risk equivalents
- Identify CHD risk factors
- Calculate 10 year risk of CHD using Framingham risk score
- Determine the risk category and goals of therapy.
NCEP ATP III GUIDELINES FOR RISK ASSESSMENT

7. 1.Diabetes Mellitus
2.Symptomatic Carotid Artery Disease
3.Peripheral Arterial Disease
4.Abdominal Aortic Aneurysm
5.CRF with Cr > 1.5 or GFR< 60
6.Multiple risk factors with a 10 year risk of CHD> 20%
CHD RISK EQUIVALENTS

8. ATP III
MAJOR CHD RISK FACTORS OTHER THAN LDL-C
• Cigarette smoking
• Hypertension: BP 140/90 mm Hg or on antihypertensive
medication
• Low HDL-C: 40 mg/dL (1.03mmol/L)*
• Family history of premature CHD (1st-degree relative):
• Male relative age 55 years
• Female relative age 65 years
• Age -Male 45 years
-Female 55 years
HDL-C 60 mg/dL (1.55mmol/L) = negative risk factor; Delete one risk factor.

10. ATP III: Updated LDL-C Goals,
Treatment Cut-Points
Grundy SM et al. Circulation. 2004;110:227-239.
<130 mg/dL
(optional:
<100 mg/dL)
<100 mg/dL
(optional:
<70
mg/dL)†
LDL-C Goal
130 mg/dL
(100–129 mg/dL:
consider drug
options)
130 mg/dL‡Moderately
high risk:
2 risk factors
(10-year risk
10%–20%)
100 mg/dL
(<100 mg/dL:
consider drug
options)
100 mg/dL‡High risk:
CHD or CHD risk
equivalents*
(10-year risk
>20%)
Consider
Drug TherapyInitiate TLCRisk Category
*CHD risk equivalents: clinical manifestations of noncoronary forms of atherosclerotic disease (transient
ischemic attacks or stroke of carotid origin >50% obstruction of a carotid artery), diabetes, and 2 risk
factors with 10-year risk >20% for hard CHD.
†The optional LDL-C goal of <70 mg/dL is favored in those at very high risk (e.g., people with diabetes, smokers)
as well as those with metabolic syndrome, acute coronary syndrome, high TG, and/or non–HDL-C <100 mg/dL.
‡Any person at high or moderately high risk with lifestyle-related risk factors is a candidate for TLC to modify
these risk factors regardless of LDL-C level.

11. ATP III: Updated LDL-C Goals,
Treatment Cutpoints (cont’d)
Grundy SM et al. Circulation. 2004;110:227-239.
Risk Category LDL-C Goal Initiate TLC
Consider
Drug Therapy
Moderate risk:
2 risk factors
(10-year risk
<10%)
<130 mg/dL 130 mg/dL 160 mg/dL
Lower risk:
0–1 risk factor
<160 mg/dL 160 mg/dL 190 mg/dL
(160–189 mg/dL:
LDL-C–lowering
drug optional)
Not modified in update

12. WHAT’S NEW ?

13. LIPIDS ADA 2014… WAS
 To get specified LDL target
Statin therapy should be added, regardless of baseline
lipid levels, for DM patients:
- With overt CVD
-Without CVD who is > 40 years old and
have ≥ 1 other CVD risk factors. (A)
 An alternative therapeutic goal :
Reduction in LDL cholesterol by 30–40% from baseline
(A)

14. Statins use is based on desired
LDL-C Intensity lowering rather than LDL target number
Adjustment of intensity of statin therapy
may be needed based on individual patient response to medication
(e.g., side effects, tolerability, LDL cholesterol levels). E
LIPIDS ADA 2015

15. LIPIDS ADA 2014… WAS
If targets are not reached;
Use combination therapy
No outcome studies; CVD outcomes or safety.
(E)

16. Combination therapy
(statin/ fibrate and statin/niacin)
has not been shown to provide additional
cardiovascular benefit above statin therapy alone
and is Not generally recommended
A
LIPIDS ADA 2015

17. 2013 ACC/AHA
GUIDELINES ON TREATMENT OF BLOOD
CHOLESTEROL TO REDUCE ATHEROSCLEROTIC
CARDIOVASCULAR RISK IN ADULTS

18. NICE CLINICAL GUIDELINE 181
GUIDANCE.NICE.ORG.UK/CG181
NICE 2014
An update of existing National Institute for Health and
Care Excellence (NICE) guidance (published in 2008)

19. STATINS INTENSITY CATEGORIES
NICE VS ACC/AHA
NICE
low intensity
20% to 30%
medium intensity
31% to 40%
high intensity > 40%
ACC/AHA
low intensity
<30%
medium intensity
30% to <50%
high intensity ≥ 50%
Targeting LDLTargeting non-HDL

20. LIPIDS ADA 2014… WAS
 An alternative therapeutic goal :
Reduction in LDL cholesterol by
30–40% from baseline (A)

21. STATINS INTENSITY CATEGORIES OF LOWERING LDL –C
NICE VS ACC/AHA

22. NICE - DYSLIPIDEMIA AND (CVD)
STATINS INTENSITY
Modest potency statins
Rosuvastatin 5-10 mg
Atorvastatin :10-20 mg
Simvastatin : 20-40 mg
Fluvastatin -XL : 80 mg
High potency statins
Rosuvastatin 20-40 mg
Atorvastatin :40-80 mg

23. 2013 ACC/AHA
GUIDELINES ON TREATMENT OF BLOOD
CHOLESTEROL TO REDUCE ATHEROSCLEROTIC
CARDIOVASCULAR RISK IN ADULTS

24. ≥ 7.5% ASCVD
10-years Risk

25. Download from : Google Play Store
Search for : ASCVD Risk
Link: Calculatorhttps://play.google.com/store/apps/details?id=org.acc.cvrisk

27. NICE CLINICAL GUIDELINE 181
GUIDANCE.NICE.ORG.UK/CG181
NICE
LIPID MODIFICATION
CARDIOVASCULAR RISK ASSESSMENT AND THE
MODIFICATION OF BLOOD LIPIDS FOR THE PRIMARY
AND SECONDARY PREVENTION OF CARDIOVASCULAR
DISEASE
ISSUED: JULY 2014
LAST MODIFIED: SEPTEMBER 2014

28. NICE GUIDELINES-2014
DYSLIPIDEMIA AND (CVD)
Do not use a risk assessment tool for people
1-With pre-existing CVD
2-Familial hyper-cholesterolemia
3- With type 1 DM
4-With CKD ; e GFR < 60 ml/min/1.73 m2 and/or albuminuria

29. NICE GUIDELINES -DYSLIPIDEMIA AND (CVD)
IDENTIFYING AND ASSESSING (CVD) RISK
Use the QRISK2 risk assessment tool to assess CVD risk for the
primary prevention of CVD in people (including type 2 DM)
older than 40 up to and including age 84 years
(review on regular basis)
QRISK2 cannot be used in people over 84 years of age.

30. NICE GUIDELINES -DYSLIPIDEMIA AND (CVD)
IDENTIFYING PEOPLE FOR FULL FORMAL RISK ASSESSMENT
DIABETIC PATIENTS
The QRISK2 risk assessment tool
Calculator is available at
http://www.qrisk.org

32. Exclude common secondary causes
of dyslipidemia before referral
(Ex:excess alcohol, uncontrolled DM, hypothyroidism,
liver disease and nephrotic syndrome)

33. DYSLIPIDEMIA AND (CVD)
Include all of the following in the assessment:
-Smoking status
-Alcohol consumption
-Blood pressure
-Body mass index or other measure of obesity
-Total-C, HDL-C, non-HDL-C and triglycerides
-HbA1c
-Renal function and e-GFR
-Transaminase level (ALT , AST )
-TSH

34. NICE : LIPID MODIFICATION THERAPY FOR THE PRIMARY AND
SECONDARY PREVENTION OF CVD
Lipid measurement and referral
A fasting sample is not needed
Measure a full lipid profile (Total-C , HDL – C , TAG ) and
(non-HDL-C ) to achieve the best estimate of CVD risk
Clinical findings
Lipid profile
Family history
=The likelihood of a familial lipid disorder

35. NICE : LIPID MODIFICATION THERAPY FOR THE PRIMARY AND
SECONDARY PREVENTION OF CVD
Lipid measurement and referral
Consider Familial hyper- cholesterolemia
and investigate if they have:
1-Total-C > 7.5 mmol/L and
2- Family history of premature CHD
Definite MI or sudden death affecting a first degree relative
before age of 55 yrs (males) or 65 yrs (females)

36. NICE : LIPID MODIFICATION THERAPY FOR THE PRIMARY AND
SECONDARY PREVENTION OF CVD
Lipid measurement and referral
Arrange for specialist assessment if
Total –C > 9.0 mmol/L or a non-HDL C > 7.5 mmol/L
even in the absence of a first-degree F.Hx of premature CHD disease
Refer for urgent specialist review if a person has a
triglyceride concentration of > 20 mmol/L
(Exclude excess alcohol or poor glycemic control)

37. DYSLIPIDEMIA AND (CVD)
PHARMACOLOGIC THERAPY FOR THE
PRIMARY AND SECONDARY PREVENTION OF CVD
Use drugs with evidence
in clinical trials of a beneficial effect on CVD morbidity and
mortality
When a decision is made to prescribe a statin
use a statin of high intensity and low acquisition cost

38. NICE GUIDELINES -DYSLIPIDEMIA AND (CVD)
STARTING A STATIN
Decide after an informed discussion
and assure patient’s knowledge about Pros/ Cons
=Individualized care
Stress the importance of TLC
and consider the patient preferences, Co-morbidities,
poly-pharmacy, general frailty, and life Expectancy

39. LIPIDS
RX RECOMMENDATIONS AND GOALS
Lifestyle modification (TLC) has been shown to
Improve the lipid profile in patients with diabetes.
(A)
This include:
- Reduction of saturated fat, trans fat, and cholesterol intake
-Increase of n-3 fatty acids, viscous fiber and plant stanols / sterols
-Weight loss (if indicated); and increased physical activity

40. NICE GUIDELINES -DYSLIPIDEMIA AND (CVD)
SECONDARY PREVENTION OF CVD
-Start statin Rx in people with CVD with Atorvastatin 80 mg
(or equivalent)
Use a lower dose of atorvastatin if any of the following apply:
Potential drug interactions
High risk of adverse effects
Patient preference
Do not delay statin in secondary prevention to manage
modifiable risk factors Ex : Person has ACS

41. NICE GUIDELINES -DYSLIPIDEMIA AND (CVD)
PRIMARY PREVENTION OF CVD
-Estimate the level of risk using the QRISK2 (when indicated)
-Exclude secondary causes
Offer Atorvastatin 20 mg for the primary prevention of CVD
to people who have a ≥ 10% (10-year) risk of developing CVD
(estimated with QRISK2 ).

42. NICE GUIDELINES -DYSLIPIDEMIA AND (CVD)
PRIMARY PREVENTION FOR PEOPLE WITH
TYPE 2 DM
Offer Atorvastatin 20 mg for the primary prevention of
CVD to people with type 2 DM who have
a ≥ 10% (10-year) risk of developing CVD
Estimate the level of risk using the QRISK2 assessment
tool

43. NICE GUIDELINES -DYSLIPIDEMIA AND (CVD)
PRIMARY PREVENTION FOR PEOPLE WITH
TYPE 1 DM
 Offer statin treatment for the primary prevention of CVD to
adults with type 1 DM who:
1- Are older than 40 years or have had DM for > 10 years or
2- Have established nephropathy or have other CVD risk factors.
>>>>>>
 Treat adults with type 1 DM
with Atorvastatin 20 mg

44. NICE GUIDELINES -DYSLIPIDEMIA AND (CVD)
PREVENTION OF CVD TO PEOPLE WITH
CKD
 Offer Atorvastatin 20 mg for the primary or secondary
prevention of CVD to people with CKD
Increase the dose if a > 40% reduction in non-HDL cholesterol
is not achieved and (e GFR ) is ≥ 30 ml/min/1.73 m2
 Agree the use of higher doses with a renal specialist if
e GFR is < 30 ml/min/ 1.73 m2.

45. DYSLIPIDEMIA AND (CVD)
STATINS
EFFICACY , SAFETY , TOLERABILITY

46. DYSLIPIDEMIA AND (CVD)
FOLLOW-UP OF PEOPLE STARTED ON STATIN TREATMENT
Measure Total-C, HDL-C and non-HDL-C in all people who have
been started on high-intensity Statin treatment at 3 months of
treatment and aim for > 40% reduction in non-HDL-C
If the non-HDL cholesterol is not reduced by > 40 % :
 Discuss adherence and timing of dose
 Optimize adherence to diet and lifestyle measures
 Consider increasing the dose
(if started on less than atorvastatin 80 mg and the person is judged to be at
higher risk because of comorbidities, risk score or using clinical judgment)

47. NICE
ADVICE AND MONITORING FOR STATINS AE
.
Statins and pregnancy/lacttion
Potential teratogenicity
Stop Statins if pregnancy is a possibility
Stop Statins 3 months before any attempt to conceive and
to not restart them until breastfeeding is finished

48. NICE
ADVICE AND MONITORING FOR STATINS AE
Advise people who are being treated with a Statin:
Do not stop statins because of an increase in blood
glucose level or HbA1c.

49. STATINS IMPACT ON RISK OF DM / DM CONTROL
 Up to 9-14 % risk of new onset DM is reported from different
meta-analysis esp. with high doses; Such effect of statins
remains modest
 Both T1D and T2D:HbA1c was slightly higher in the group
treated with statins
(7.53% v.s. 7.41% . Mean difference was 0.12%, (P=0.003).
 CV events were reduced by 16% in the group treated with
intensive statin ;The efficacy of statins in reducing CV outcomes
in T2D is well-established and of major importance to offset
such HbA1c changes
Use of statins in primary prevention in T2D should not be changed.

50. NICE
ADVICE AND MONITORING FOR STATINS AE
Statins and creatine kinase (CK)
1- Do not measure CK levels in asymptomatic people who are being
treated with a statin
2- If patient has suggestive myopathy symptoms ( persistent
generalized unexplained muscle pain, associated or not with
previous lipid-lowering therapy) before or after start of a statin
If they have, measure creatine kinase (CK) levels

51. NICE
ADVICE AND MONITORING FOR STATINS AE
Statins and creatine kinase (CK)
3- If patient has suggestive myopathy symptoms measure (CK):
If CK levels are > 5 times the ULN, re-measure it after 7 days.
If CK levels are still 5 times ULN, do not start statin treatment
If CK levels are raised but < 5 times ULN, start statin treatment at a
lower dose
4- If statin therapy was tolerated for > 3 months ; R/O other causes
of muscle pain or weakness and raised CK

52. NICE
ADVICE AND MONITORING FOR STATINS AE
Statins and Liver Transaminases
1- Measure baseline liver transaminase enzymes (ALT or AST ) ,at
baseline , 3 and 12 months of starting a statin
-No more testing unless clinically indicated
2- Do not routinely exclude from statin therapy people who have
liver transaminase levels that are raised but are < 3 times ULN

53. NICE
INTOLERANCE OF STATINS
If a patient is un-able to tolerate a high-intensity statin;
Treat with the maximum tolerated dose

54. NICE
INTOLERANCE OF STATINS
Seek specialist advice (by telephone, virtual clinic or referral)
about options for treating people at high risk of CVD:
CKD
Type 1 diabetes
Type 2 diabetes
Genetic Dyslipidemia
CVD, who are intolerant to 3 different statins

55. NICE ADVICE ON
OTHER LIPID LOWERING AGENTS /COMBINATIONS

56. NICE
COMBINATION RX
Do not routinely offer Fibrates and
Do not offer Nicotinic acid (niacin) or Bile acid sequestrants (anion
exchange resins) or omega-3 fatty acid compounds for the
prevention of CVD to any of the following group of patients :
-Treated for primary prevention
-Treated for secondary prevention
-With CKD
-With type 1 DM
-With type 2 DM
[new 2014]

57. NICE
COMBINATION THERAPY FOR PREVENTING CVD
Ezetimibe treatment in addition to Statins
should be considered
For people with primary hyper- cholesterolemia
(heterozygous familial and non-familial hyper- cholesterolemia )

58. TAKE HOME MESSAGES

59. DYSLIPIDEMIA AND (CVD)
TAKE HOME MESSAGES
Guidelines are Guidelines
Should not eliminate our clinical judgment
Patient centered personalized care
Safest practice and
best shared-decision

60. DYSLIPIDEMIA AND (CVD)
TAKE HOME MESSAGES
 Risk assessment tools
High risk groups = No need to calculate Risk
All others : Risk calculator ;Not “eyeballing” them !!
 Use (non-HDL-C)
(=Total-C – HDL-C) rather than LDL-C ;No need to fast
Or
Fasting lipid profile : LDL-C

61. 1.ASCVD / CHD equivalent
2-Diabetes Mellitus
3-Severe Dyslipidemia –Familial
4-CKD
5- Risk calculator : over next 10yrs
HIGH CVD RISK GROUPS - SUMMARY

62. NICE VS ACC/AHA VS ATP-III
NICE
low intensity
20% to 30%
medium intensity
31% to 40%
high intensity > 40%
ACC/AHA
low intensity
<30%
medium intensity
30% to <50%
high intensity ≥ 50%
Targeting LDLTargeting non-HDL
ATP-III
LDL target
Reduction in LDL-C
30–40%
from base line

63. DYSLIPIDEMIA AND (CVD)
TAKE HOME MESSAGES
 Lipid-lowering drugs
-Statins for primary and secondary prevention
-Use the highest tolerated dose
-Combination Rx ?
 Use simultaneously guidelines on
other modifiable risk factors for CVD (like HTN , DM)

64. NICE GUIDELINES DYSLIPIDEMIA AND (CVD)
GUIDELINE DEVELOPMENT GROUP (GDG)
1-Use medium intensity statins for Primary prevention
Atorvastatin 20 mg
2- Use high intensity statin for Secondary prevention
Atorvastatin 80 mg
3- Do it safely
Assess on regular basis for
tolerance and adverse effects