Transcript NCEP ATP III Cholesterol Guidelines and Updates

NCEP ATP III
Cholesterol Guidelines
and Updates
Anoop Agrawal, M.D.
Med-Peds Continuity Clinic
Baylor College of Medicine
Background
Adult Treatment Panel of the National
Cholesterol Education Program issued
their third guideline for cholesterol
management in 2001 - known as ATP III.
Since publication, 5 major clinical trials of
statin therapy have been published.
This has resulted in an addendum to
ATP III published in July 2004.
Next update (ATP IV) expected in
2009.
Background cont. - The 5 studies:
Heart Protection Study - revealed 25% reduction in
mortality regardless of baseline LDL levels
ALLHAT - did not show statin benefit in those with
HTN; result attributed to use of pravastatin as study drug
PROVE IT - intensive statin therapy following acute
coronary syndrome is superior
PROSPER - demonstrated statin benefit even in the
elderly
ASCOT-LLA - LDL lowering with atorvastatin had
considerable CVD risk reduction in those with multiple
CVD risk factors. (in contrast to ALLHAT)
NCEP Major Risk Factors
Classification of an individual’s risk for
cardiac events is based upon five risk
factors:
smoking
hypertension
low HDL (<40)
family history- 1st degree relative with
MI <55yo for male, <65 yo for female
age: male >45 yo, female >55 yo
**HDL > 60: reduction of 1 risk factor
CVD Risk Assessment
Based upon the 10 year cardiovascular risk
score.
>20% and/or coronary heart disease
(CHD) equivalents: high risk
very high risk: CHD + other risk factors
10-20% and 2+ risk factors: moderate high
<10% and 2+ risk factors: moderate risk
0-1 risk factor: lower risk
calculated using Framingham risk score
CHD Equivalents
What are the recognized Coronary Heart
Disease equivalents?
Diabetes Mellitus
Peripheral Arterial Disease
Symptomatic Carotid Artery Disease
(TIA or stroke of carotid origin)
Abdominal Aortic Aneurysm
10 yr risk for CHD >20% with 2+ risk
factors
Example of
Framingham risk
assessment calculator
Found at
www.nhlbi.nih.gov/gui
delines/cholesterol
can also google ’10
year cvd’ and will be
first hit
ATP III Guidelines 2004
LDL level to LDL level to
Category
LDL goal
begin TLC
begin statins
High risk
<100 mg/dl; optional
<70 in very high risk
≥100 mg/dl
100 mg/dl
Moderately
high risk
<130 mg/dl; optional
<100mg/dl
≥130 mg/dl
≥ 130 mg/dl; 100129 consider*
Moderate risk
<130 mg/dl
≥130 mg/dl
≥ 160 mg/dl
Lower risk
<160 mg/dl
≥160 mg/dl
≥ 190 mg/dl
*for moderate high risk patients with 100-129 baseline or after TLC: initiation of LDL lowering drug to achieve
LDL <100 mg/dl is an option
Adapted from Third report of the National Cholesterol Education Program (NCEP) Expert Panel on detection, evaluation, and treatment of high blood cholesterol
in adults (Adult Treatment Panel III). Circulation 2002; 106:3143; with modifications from Grundy, SM, Cleeman, JI, Merz, CN, et al, Circulation 2004; 110:227.
Case V.H.
V.H. is a 60 year old male
with CAD, DM II, and
tobacco use. His baseline
lipid panel is:
Cholesterol
210
HDL
40
LDL
148
Triglycerides
180
What is your recommendation
for managing his cholesterol?
A. TLC and simvastatin 20mg
B. TLC and vytorin 10/40
C. TLC and atorvastatin
40mg
D. TLC for 3 months, then
reevaluate
TLC: therapeutic lifestyle changes
Case V.H. cont...
Mr. V.H.’s 10 yr CVD risk places him at
>20%. Having CAD and 2 additional
risk factors promotes him to the very high
risk group.
His LDL goal is <100 with the option to
achieve LDL < 70 mg/dl
In selecting a statin for high risk patients,
intensity of therapy needs to achieve at
least 40% reduction in LDL.
Remember not all statins are created
equal.
2004 Addendum to ATP III
For High Risk:
Prior to addendum: The treatment goal for
high-risk patients was an LDL < 100. Drug
therapy was initiated only if LDL ≥ 130.
UPDATE: Overall goal is still an LDL <
100. There is a therapeutic option to set
the goal at an LDL < 70 for very high-risk
patients
Also initiate drug therapy if LDL ≥100; also have the
option to add on if baseline already < 100.
Case M.H.
M.H. is a 48 yo female with
uncontrolled HTN (today
160/80) and a smoker. Her FH is
significant for her mother with heart
disease at age 61. She currently is
not on lipid therapy.
Her baseline lipid panel
Total Chol
210
LDL
120
HDL
40
Trigs
180
Which of the following do
you recommend?
A. TLC only, she is at
goal
B. simvastatin 20mg
C. omega-3 fatty acids
D. ezetimibe 10mg
Case M.H. continued...
What is her classification and goal LDL?
Based on her 10 yr risk score (11%) she
is Moderate High risk, goal LDL < 130.
But <100 is therapeutic option if
baseline is already <130 and has
uncontrolled risk factors.
Simvastatin 20mg would be sufficient to
reach goal.
Why not ezetimibe (Zetia)?
Not first-line choice. Recent study (ENHANCE) showed zetia did
lower LDL, but did not show slowing or regression of atherosclerosis.
2004 Addendum to ATP III
In Moderate High Risk:
Prior to addendum: The treatment goal was an LDL
< 130, and drug treatment was recommended if LDL is
130 or higher.
UPDATE: The overall goal for moderately highrisk patients is still an LDL < 130. There is a
therapeutic option to set the treatment goal at an
LDL < 100, and to use drug treatment if LDL is
100-129.
2004 Addendum to ATP III
For both High and Moderate High:
Prior to addendum: Guidelines did not explicitly
emphasize achieving a certain percentage lowering
of LDL cholesterol.
Update: Advises that the intensity of LDLlowering drug treatment in high-risk and moderately
high-risk patients be sufficient to achieve at least a
30-40% reduction in LDL levels.
Comparison of the efficacy of
statin drugs
Each doubling of the
dose of a statin, gives
only an additional 6%
reduction of LDL from
initial baseline at which
statin was initiated.
Case 3: Myalgias due to statin
A 56 yo female is complaining about
myalgias due to her therapy with
simvastatin 40mg. Her LDL is 146. Her
goal LDL is <100. Which of the
following are viable options?
a. reduce simvastatin to 20mg nightly
b. change to atorvastatin 40mg nightly
c. change to niacin
d. change to ezetimibe 10mg daily
Case 3
: Myalgias due to statin
a: Myalgias are dose dependent response to statins.
Lowering the dose may prevent the symptoms. In this case,
reducing the dose would not help reach goal
b: Myalgias are not seen with every statin; no clear reason
for this patient-variable response. If patient agreeable,
then try another statin. Atorvastatin 40mg will be more
effective than simvastatin 40mg at reaching goal.
c: Niacin does not help lower LDL.
d: Ezetimibe is a option if patient refuses to try another
statin or has myalgias with another statin
Case 3: Myalgias due to Statin
Clinical Pearls:
Frequency of statin-related myalgias with
normal CK is approximately 10-20%.
Occurrence of myalgias is dose-related
Ezetimibe can lower LDL by 20%
Bile acid-resins are another alternative
treatment option (colesevelam)
New FDA: Simvastatin
Data fro SEARCH trial
incidence of adverse CV events was
25.7% in simvastatin 20mg group vs.
24.5% in 80 mg group
Myopathy - 52 patients in 80-mg
group vs. 1 in the 20mg group
Rhabdo - 44
FDA: Simvastatin
labeling
Simvastatin is more prone to drug
interactions than other statins because it
is extensively metabolism by CYP3A4
Rates of rhabdomyolysis with simvastatin
80mg is higher than with 80mg atorvastatin
or 20/40mg of rosuvastatin.
Summary
Recent updates affect patients in high and
moderate high risk categories.
Encourages more aggressive lipid control due
to evidence of significant reduction in vascular
events regardless of baseline level of LDL.
Some LDL goals are still optional. In general,
patients with high and moderate high risk are
targeted to lower LDLs.
Summary
When initiating statin therapy, initial dose
should target at least a 30-40% reduction
in LDL.
If goal LDL requires more than a 50%
reduction of baseline, then goal will likely
be unattainable with current options.