2013 ACC/AHA Blood Cholesterol
Treatment Guidelines“Intensity Of Statin Therapy”
Aim to Reduce RISK … not at Target levels
DR.PRAVEEN NAGULA
Scope of guideline• to reduce atherosclerotic cardiovascular disease(ASCVD)risk
{RCTs,systematic analysis and metaanalysis of RCTs}.
• ASCVD – coronary heart disease(CHD),stroke,and peripheral arterial disease,all of presumed atherosclerotic origin.
• to provide strong evidence-based foundation.• only evidence from statin RCTs were used to develop
guidelines.****
• Comprehensive approach to lipid management for purposes with relation to ASCVD reduction only,not for complex lipid disorders.
What do present guidelines say.....
Patient centered approach rather than
one treatment fits all
What’s new in the guideline…?
Benefits of Statins• High intensity therapy – lowering LDL cholesterol by >50%.• Moderate intensity therapy - lowering LDL cholesterol by 30-50%.• Reduces ASCVD events across the spectrum of baseline LDL-C
levels > 70 mg/dl.• Relative reduction in ASCVD risk is consistent for primary and
secondary prevention.
Absolute reduction in ASCVD events is proportional to baseline absolute ASCVD risk.
Statin therapy only for individuals at increased ASCVD risk .
Who are to be benefited by Statins ?????
Primary prevention of ASCVD
• Based on the estimated absolute 10 yr risk of ASCVD (non fatal MI,CHD death,nonfatal and fatal stroke)…
• The omnibus CV risk calculator for
Pts without clinical ASCVD and LDL 70-189mg/dl Estimates 10 yr risk of ASCVD In diabetics ,for primary prevention
Not in pts with clinical ASCVD
Statin treatment:Recommendations
Primary prevention in patients with LDL>190mg/dl
Management
Evaluate for cause
Age>21 years LDL-C>190mg/dl
primary
High dose statin
I B
Maximum tolerated
dose
I B
LDL-C reduction of atleast 50%
IIaB
secondary
Evaluate and treat
accordingly
Primary prevention in patients with diabetes
Statins
Age
DiabetesLDLcholesterol70-189 mg/dl
40-75 yrs
Moderate intensity statins
I A
High intensity statins
with risk >7.5%
IIa B
<40 yrs,>75yrs
Balance between ASCVDbenefits and
adverse effects
IIa C
Age of the patient
10 yr ASCVD risk estimate
Patients without diabetes,primary preventionLDLcholesterol
70-189 mg/dl
>7.5%
40-75 yrs
Moderate to high intensity
therapy
I A
>75yrs
Assess risk,
benefits
5-7.5%
40-75 yrs
Moderate intensity therapy
IIa B
>75 yrs
Assess risks
benefits
Statins in Heart Failure,Hemodialysis patients
LDLcholesterol
>190 mg/dl
Pt had CAD, HTN,smoker,not on statins
Age 45 yrs
Start Statins to the
maximum tolerated
dose
Age 75 yrs
Assess risk,benefits
Pt diabetic,no
CAD,ASCVDrisk
>7.5%
High intensity statins
Pt not diabetic,noCAD
Evaluate secondary
causes
High dose statin
therapy
70-189 mg/dl
Pt CAD
Statins
Pt diabetic
Moderat dose
statins
Pt no h/o
CAD,DM2,
risk <7.5%
Assess risk,
benefits
Pt having CKD
No EBT for
statins
High- Moderate – and Low –Intensity Statin Therapy
Clinical application by Statin dose
STATINSHIGH INTENSITY THERAPY
MODERATE INTENSITY THERAPY
LOW INTENSITY THERAPY
Daily dose lowers LDL-C on average,by approximately ≥50%
Daily dose lowers LDL –C on average,by approximately 30-50%
Daily dose lowers LDL –C <30%
Atorvastatin (40) 80 mg
Atorvastatin 10 (20) mg
Simvastatin 10 mg
Rosuvastatin 20 (40) mg
Rosuvastatin (5) 10 mg
Pravastatin 10-20 mg
Simvastatin 20-40 mg
Lovastatin 20 mg
Pravastatin 40 (80) mg
Fluvastatin 20-40 mg
Lovastatin 40 mg Pitavastatin 1 mgFluvastatin XL 80 mgFluvastatin 40 mg bidPitavastatin 2-4 mg
Safety recommendations of statinsNHLBI ACC/AHA
CORLOE
1.Creatine Kinase,routinely not needed A III no benefiit A
2.Baseline CK in pts at risk of events E IIa C3.Baseline ALT before initiating statins B I B4.Decreasing the statin dose,if 2 consecutive values of LDL-C <40 mg/dl.
C IIb C
5.Simvastatin at 80 mg daily harmful B III harm A6.New onset diabetes on statin therapy,continue statins
B I B
7.If muscle symtpoms develop,discontinue,use again
E II a C
8.Confusional state,see secondary causes
E II b C
Monitoring statin treatment
What do guidelines say..
Lifestyle is the foundation for ASCVD risk reduction
Adhering to a healthy heart diet,Regular exercise habitsAvoidance of tobacco productsMaintenance of healthy weight
• Remains critical component both prior to and in concert with the use of cholesterol lowering drug therapies
What is the fate of nonstatins in guidelines
are they Ignored??
Niacin
Baseline hepatic transaminases,FBS,HBA1c
Hepatic transaminases elevations are higher
>2-3ULN
Persistent severe cutaneous symptoms,hyperglycemia,
acute gout
New onset AF,weight loss
Niacin
Start at low dose
Take niacin with food or aspirin
500 mg ER to 2000mgER
Bile acid sequestrants
Baseline TG
>300 mg/dl
250-299 mg/dl
Cholesterol absorption inhibitors
Baseline hepatic transaminases
Discontinue if ALT>3 times
occur
Fibrates
Gemfibrozil in patients on statin therapy
If TG>500mg/dl and benefit>risks
GFR<30 ml/min
Omega 3 fatty acids
Severe hypertriglyceridemia
Evaluate GI disturbances
I AIIa/IIbBIII
Secondary causes of hyperlipidemiaSecondary cause Elevated LDL - C ELEVATED TRIGLYCERIDES
DIET Saturated or trans fats,wt gain,anorexia
Wt gain,very low fat diets, high intake of refined carbohydrates,excessive alcohol intake
DISEASES Biliary obstruction ,nephrotic syndrome
Nephrotic syndrome, CKD,lipodystrophies
DRUGS Duiretics,cyclosporine,glucocorticoids,amiodarone
Oral estrogens,glucocorticoids,bile acid sequestrantsprotease inhibitors,retinoic acid,sirolimus,beta blockers,thiazides
ALTERED METABOLISM
Hypothyroidism,Obesity,pregnancy
Diabetes, hypothyroidism,obesity, pregnancy
Statins,niacin,ezetimbe C/I in pregnancy,lactation
Evolution of guidelines
NCEPATP I1988
NCEPATP II1993
NCEPATPIII2001
NCEPATP III
REVISED 2004
NCEPATP IV2013??
ACC/AHA2013
Basis for the New Guidelines
RCTs reviewed showed a consistent reduction in ASCVD events from Statins therapy in secondary and primary prevention, no ASCVD event reduction in those with NYHA class II-IV HF or receiving maintenance hemodialysis.
Only fixed doses of statins with placebo or untreated controls,comparison of high dose with moderate intensity statins.
No evaluation of the effect of titrated (dose adjusted) statin treatment to achieve prespecified LDL- C or non HDL-C goals.
Use of niacin to additionally lower non HDL –C,once an LDL target was achieved,did not further reduce ASCVD outcomes.(AIM HIGH trial)
The intensity of statin therapy is appropriate on those most likely to benefit.
• Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med 2008;359:2195-207 • AFCAPS-TEXCAPS, JAMA 1998;279:1615–1622• MEGA trial, Lancet 2006;368:1155–1163.
3 CQs –CQ1 - secondary,(19RCT)CQ2 – primary prevention (6RCT)CQ3 – comprehensive management,safety of each drug
Why other approaches ignored???
1.Treat to Target – widely used for past 15 yrs What is the target ? What is the additional risk reduction beyond one target lower
than other? adverse effects from multidrug therapy that occur in achieving
goal undertreatment with statins, overtreatment with nonstatins 2.lowest is best adverse effects? 3.lifetime risk long term follow up >15 yrs? statins>10yrs?
Why Target level therapy ignored..how came the picture of statin benefit groups?
Hypothesis or Evidence based..Myth or reality
A.Secondary Prevention Evidence – high intenisty therapy to maximally lower LDL –C than using a
target.
Ex – LDL –C 78mg/dl on a dose of atorvas 80 mg/dl –receiving EBT.
No data to show that adding a nonstatin drug to high intenisty statin therapy will provide incremental ASCVD risk reduction benefit with acceptable margin of safety.(AIM HIGH,ACCORD).
This patient may be exposed to adverse effects if started of a drug with no evidence of benefit,just because his LDLis more than arbitrarily level.
This is treated as a case of failure..for a lag of 8 mg/dl..Is it justifiable ???
AIM HIGH trial NewEngl J Med 2011;365:2255-67
ACCORD, N Engl J Med 2010;362:1563–74.
B.FH with LDL –C >190 mg/dl many does not achieve <100mg/dl. maximum may be 120 mg/dl on 3 drugs. These pts may have fallen short of target ,but their LDL –C
>50% ,more ASCVD risk reduction. Not treatment failures.C.Type2Diabetes : have lower LDL-C than with without diabetes. goal directed therapy encourages low statin doses,use of drugs
for addressing HDL-C/high TG. maximally tolerated therapy to be given primary importance.D.Estimated ASCVD >7.5%
Cholesterol Treatment Trialists Collaboration, Lancet 2012;380:581–90. Taylor F, Ward K, Moore TH et al. 2011:CD004816
Limitations• Clinical judgement required in pts,for whom RCT evidence is
insufficient• Younger adults< 40 yrs with <7.5% ASCVD risk for 10
yrs,high lifetime risk.• HIV pts,rheumatological pts,IBD pts.• RCTS,Systematic reviews,meta analysis of RCTs were taken
into consideration.
New Drugs
• Cholesterol ester transfer protein (CETP) inhibitors - Anacetrapib(DEFINE,REVEAL), dalcetrapib
• Ab to pro-protein convertase subtilisin/kexin 9 (PCSK9).
• Apolipoprotein B synthesis inhibitors - Mipomersen
• Microsomal triglyceride transfer protein (MTP) inhibitors,
• Thyroid hormone analogue Eprotirome
Future.. Primary prevention in >75 yrs age Alternate treatment strategies. Effectiveness of submaximal doses of statins vs nonstatins in
intolerant pts Evaluation of the incidence of new onset diabetes associated
with statin therapy. Outcomes of RCTs of new lipid modifying agents to determine
the incremental ASCVD reduction when added to statin therapy.
Future updates required for..
1.The treatment of Hypertriglyceridemia. 2.Use of NonHDL-C in decision making. 3.Whether on-treatment markers such as
apoB,Lp(a),LDLparticles are useful in guiding decisions. 4.Best approaches to use noninvasive imaging for refining
risk estimates to guide treatment. 5.Optimal age for starting treatment for reducing lifetime risk
of ASCVD. 6.What to do in pts with HF,hemodialysis. 7.Long term effects of statin associated new onset diabetes and
management.
Conclusions Patient centered approach is to be given importance rather than one treatment fits all concept. Statins to be given at high intenisty,moderate intensity doses but not
with target levels of attainment. Nonstatins give no ASCVD benefit in pts with high intensity statin
therapy. Use of lipoprotein a ,non HDLcholesterol levels assessment is not
recommended. Pts without ASCVD should be started of the statins after assessing 10 yr
risk by omnibus calculators. New onset diabetes due to statins needs further assessment in future. New drugs in pipeline,RCT s required for their incremental benefit in
ASCVD risk reduction when added to statins Lifestyle modification remains the key concept of the management of
blood cholesterol.
THANK YOU