Common Questions in
Lipids 2010
Mehul Bhatt, MD
Athens Heart Center
Contemporary Guidelines
(simple enough)
National Cholesterol Education Program (NCEP) 2004
LDL
< 70-100 mg/dL for CAD and CAD-equivalent risk factors
< 100-130 mg/dL for 2+ CAD risk factors
< 160 mg/dL for 0-1 CAD risk factor
HDL
> 40 mg/dL
Triglycerides
< 200 mg/dL
Contemporary Guidelines
(simple enough)
First: treat LDL . . .
Second: HDL > 40 . . .
Third: Triglyceride < 200
But…what are common
lipid questions in 2010?
NCEP guidelines lag behind contemporary lipidology
Common issues:
Best statin
Coenzyme Q-10
Niacin
Ezetimibe
Nutritional supplements
What is the best statin?
6 statins available
3 name-brand: atorvastatin (Lipitor™), fluvastatin
(Lescol™), rosuvastatin (Crestor™)
3 generic: lovastatin (Mevacor™), pravastatin
(Pravachol™), simvastatin (Zocor™)
Efficacy of statins in reducing LDL and CV events
undisputed
Few head-to-head statin trials
What is the best statin?
Potency
Reduction in LDL at
lower dose
Achieve goal LDL < 70100
Linear decreasing LDL at
higher dosages
Rosuvastatin>
Atorvastatin, Simvastatin>
Fluvastatin, Lovastatin,
Pravastatin
From Cannon et al. NEJM 2001
What is the best statin?
Best data in prevention of clinical events:
Pravastatin
Simvastatin
Atorvastatin
Superior to low dose pravastatin
MIRACL, PROVE-IT: improved clinical outcomes in the
highest risk patients (during acute coronary syndromes)
Rosuvastatin
JUPITER: improved clinical outcome in low-risk patients
with elevated CRP
What is the best statin?
Prevention of cardiovascular events:
JUPITER: Rosuvastatin prevents
cardiovascular events in low risk
patients
PROVE-IT TIMI 22:
Atovastatin superior to
pravastatin after acute coronary
syndromes
From Cannon et al. NEJM 2001 and Ridker et al. NEJM 2008
What is the best statin?
Atherosclerotic plaque stabilization/regression:
REVERSAL Trial 2004 (atorvastatin)
ASTERIOD Trial 2006 (rosuvastatin)
From Nissen et al. JAMA 2004
What is the best statin?
Pleotropic effects
Anti-inflammatory effects in atherosclerotic plaque
Anti-thrombotic
Improve endothelial function
Increasing nitric oxide (vasodilator)
Inhibits endothelin-1 (vasoconstrictor)
Most data with high-dose atorvastatin and
rosuvastatin
Perhaps mediated through CRP and/or sCD40
What is the best statin?
Pleotropic effects:
High-dose atorvastatin and rosuvastatin have most
proven effect on CRP in large trials
From Ridker et al. NEJM 2005
What is the best statin?
Summary:
Benefits of statins undisputed
More benefits in higher risk patients
Acute coronary syndromes, high-CRP, multiple risk
factors. . .
Atorvastatin and Rosuvastatin:
Most recent large trials
Atherosclerotic plaque stabilization/regression data
Are they better than less expensive alternatives?
Or do they have more recent data?
Does Coenzyme-Q10 work?
CoQ10 = Ubiquinone
CoQ10: Fat-soluble
compound found in
hydrophobic portion of
mitochondrial membrane
Approx. 10% rate of statin
related myalgia
Statins reduce Co-Q10
levels 25-40%
Depletion of skeletal
muscle mitochondrial CoQ10 may lead to myalgia
and myopathy
From Marcoff et al. JACC 2007
Does Coenzyme-Q10 work?
Co-Q10 supplementation increases plasma level in
patient taking statins
Multiple observational and anecdotal reports of
improvement in myalgia with Co-Q10
2 small randomized trials in patients with history of
myalgia did show benefit
Overall, Co-Q10 harmless, inexpensive, and may
reduce statin-related myalgia
Niacin, revisited…
Niacin used clinically in heart disease for over 50
years (pre-statin era)
1st randomized controlled trial in lipids in CAD:
Coronary Drug Project: Clofibrate and niacin in
coronary heart disease. JAMA 1975;
8,341 males from 31-64 years old with history of MI
Randomized to conjugated estrogens, clofibrate,
dextrothyroxine, niacin (3000 mg/day), or placebo
Niacin had early reduction in rates of MI and a
mortality benefit that was maintained at 15-year
follow-up!
From JAMA 1975 and Canner et al. JACC 1986
Niacin, revisited…
Niacin = Nicotinic acid = Vitamin B3
In high doses decreases LDL, increases HDL
Most common side effects are flushing, itching, rash
Over-the-counter; relatively inexpensive
Niacin extended-release tablets: available since 1997 (Niaspan)
does reduce flushing rates
NSAIDs 30 min before niacin and extended-release niacin are
shown to reduce flushing
Niacin, revisited…
ARBITER 6-HALTS
CAD patients with LDL < 100, HDL < 50-55
statin + extended-release niacin (2000 mg/day)
- versus statin + ezetimibe
Lower LDL with ezetimibe
Higher HDL and lower TG with niacin
BUT OUTCOMES. . .
From Taylor et al. NEJM 2009
Is there any value to ezetimibe?
Ezetimibe (Zetia)
Decreases
intestinal
absorption of
cholesterol
Effective in
reducing LDL
But, does not
reduce plaque or
clinical event
Probably only
useful when statins
not toleratated
Nutritional supplement
therapy
SUPPLEMENT
EFFECT
Red yeast rice,
Plantphytosterols and phytostanols
(vegetable oil, nuts, legumes,
whole grains)
Reduce LDL
Omega 3 fatty acids
(fish oils, certain plants/nuts)
Reduce TG, possibly raise HDL,
possibly reduce CV event rates
Green tea catechins and black tea
theaflavins
Possibly lower LDL
Guggulipids, policosanol, cinnamon,
garlic
No effect
Summary
Treat CAD and CAD-equivalent patients to
LDL goal < 70-100
“Best statin”: atorvastatin and rosuvastatin have
most recent data with pleotrophic effects and plaque
stabilization/regression
Niacin has important role in lipid management
Some quality nutritional supplement have value
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