Common Common Questions in Questions in Lipids 2010Lipids 2010

Mehul Bhatt, MDMehul Bhatt, MDAthens Heart CenterAthens Heart Center

Contemporary GuidelinesContemporary Guidelines(simple enough)(simple enough)

National Cholesterol Education Program (NCEP) National Cholesterol Education Program (NCEP) 20042004

LDLLDL< 70-100 mg/dL for CAD and CAD-equivalent risk < 70-100 mg/dL for CAD and CAD-equivalent risk factorsfactors< 100-130 mg/dL for 2+ CAD risk factors< 100-130 mg/dL for 2+ CAD risk factors< 160 mg/dL for 0-1 CAD risk factor< 160 mg/dL for 0-1 CAD risk factor

HDLHDL> 40 mg/dL> 40 mg/dL

TriglyceridesTriglycerides< 200 mg/dL< 200 mg/dL

Contemporary Contemporary GuidelinesGuidelines

(simple enough)(simple enough)First: treat LDL . . .First: treat LDL . . .

Second: HDL > 40 . . .Second: HDL > 40 . . .

Third: Triglyceride < 200Third: Triglyceride < 200

But…what are But…what are common lipid common lipid questions in questions in

2010?2010?NCEP guidelines lag behind NCEP guidelines lag behind contemporary lipidologycontemporary lipidology

Common issues:Common issues:Best statinBest statin

Coenzyme Q-10Coenzyme Q-10

NiacinNiacin

EzetimibeEzetimibe

Nutritional supplementsNutritional supplements

What is the best What is the best statin?statin?

6 statins available6 statins available3 name-brand: atorvastatin (Lipitor™), 3 name-brand: atorvastatin (Lipitor™), fluvastatin (Lescol™), rosuvastatin fluvastatin (Lescol™), rosuvastatin (Crestor™)(Crestor™)

3 generic: lovastatin (Mevacor™), 3 generic: lovastatin (Mevacor™), pravastatin (Pravachol™), simvastatin pravastatin (Pravachol™), simvastatin (Zocor™)(Zocor™)

Efficacy of statins in reducing LDL and CV Efficacy of statins in reducing LDL and CV events undisputedevents undisputed

Few head-to-head statin trialsFew head-to-head statin trials

What is the best What is the best statin?statin?

PotencyPotencyReduction in LDL at Reduction in LDL at lower doselower doseAchieve goal LDL < Achieve goal LDL < 70-10070-100Linear decreasing Linear decreasing LDL at higher LDL at higher dosagesdosages

Rosuvastatin>Rosuvastatin>Atorvastatin, Atorvastatin,

Simvastatin>Simvastatin>Fluvastatin, Lovastatin, Fluvastatin, Lovastatin,

PravastatinPravastatin

From Cannon et al. NEJM 2001

What is the best What is the best statin?statin?

Best data in prevention of clinical events:Best data in prevention of clinical events:

PravastatinPravastatin

SimvastatinSimvastatin

AtorvastatinAtorvastatinSuperior to low dose pravastatinSuperior to low dose pravastatin

MIRACL, PROVE-IT: improved clinical MIRACL, PROVE-IT: improved clinical outcomes in the highest risk patients outcomes in the highest risk patients (during acute coronary syndromes)(during acute coronary syndromes)

RosuvastatinRosuvastatinJUPITER: improved clinical outcome in low-JUPITER: improved clinical outcome in low-risk patients with elevated CRPrisk patients with elevated CRP

What is the best What is the best statin?statin?

Prevention of cardiovascular events:Prevention of cardiovascular events:

From Cannon et al. NEJM 2001 and Ridker et al. NEJM 2008

PROVE-IT TIMI 22: Atovastatin superior to pravastatin after acute coronary syndromes

JUPITER: Rosuvastatin prevents cardiovascular events in low risk patients

What is the best What is the best statin?statin?

Atherosclerotic plaque Atherosclerotic plaque stabilization/regression:stabilization/regression:

REVERSAL Trial 2004 (atorvastatin)REVERSAL Trial 2004 (atorvastatin)

ASTERIOD Trial 2006 (rosuvastatin)ASTERIOD Trial 2006 (rosuvastatin)From Nissen et al. JAMA 2004

What is the best What is the best statin?statin?

Pleotropic effectsPleotropic effectsAnti-inflammatory effects in atherosclerotic Anti-inflammatory effects in atherosclerotic plaqueplaque

Anti-thromboticAnti-thrombotic

Improve endothelial functionImprove endothelial functionIncreasing nitric oxide (vasodilator)Increasing nitric oxide (vasodilator)

Inhibits endothelin-1 (vasoconstrictor)Inhibits endothelin-1 (vasoconstrictor)

Most data with high-dose atorvastatin and Most data with high-dose atorvastatin and rosuvastatinrosuvastatin

Perhaps mediated through CRP and/or sCD40Perhaps mediated through CRP and/or sCD40

What is the best What is the best statin?statin?Pleotropic effects:Pleotropic effects:

High-dose atorvastatin and rosuvastatin High-dose atorvastatin and rosuvastatin have most proven effect on CRP in large have most proven effect on CRP in large trialstrials

From Ridker et al. NEJM 2005

What is the best What is the best statin?statin?

Summary:Summary:Benefits of statins undisputedBenefits of statins undisputed

More benefits in higher risk patientsMore benefits in higher risk patientsAcute coronary syndromes, high-CRP, Acute coronary syndromes, high-CRP, multiple risk factors. . .multiple risk factors. . .

Atorvastatin and Rosuvastatin:Atorvastatin and Rosuvastatin:Most recent large trialsMost recent large trials

Atherosclerotic plaque Atherosclerotic plaque stabilization/regression datastabilization/regression data

Are they better than less expensive Are they better than less expensive alternatives?alternatives?

Or do they have more recent data?Or do they have more recent data?

Does Coenzyme-Q10 Does Coenzyme-Q10 work?work?

CoQ10 = UbiquinoneCoQ10 = Ubiquinone

CoQ10: Fat-soluble CoQ10: Fat-soluble compound found in compound found in hydrophobic portion hydrophobic portion of mitochondrial of mitochondrial membranemembrane

Approx. 10% rate of Approx. 10% rate of statin related myalgiastatin related myalgia

Statins reduce Co-Statins reduce Co-Q10 levels 25-40%Q10 levels 25-40%

Depletion of skeletal Depletion of skeletal muscle mitochondrial muscle mitochondrial Co-Q10 may lead to Co-Q10 may lead to myalgia and myalgia and myopathymyopathy

From Marcoff et al. JACC 2007

Does Coenzyme-Q10 Does Coenzyme-Q10 work?work?

Co-Q10 supplementation increases Co-Q10 supplementation increases plasma level in patient taking statinsplasma level in patient taking statins

Multiple observational and anecdotal Multiple observational and anecdotal reports of improvement in myalgia with reports of improvement in myalgia with Co-Q10 Co-Q10

2 small randomized trials in patients 2 small randomized trials in patients with history of myalgia did show benefit with history of myalgia did show benefit

Overall, Co-Q10 harmless, inexpensive, Overall, Co-Q10 harmless, inexpensive, and may reduce statin-related myalgiaand may reduce statin-related myalgia

Niacin, revisited…Niacin, revisited…Niacin used clinically in heart disease for over Niacin used clinically in heart disease for over 50 years (pre-statin era)50 years (pre-statin era)

11stst randomized controlled trial in lipids in CAD: randomized controlled trial in lipids in CAD:Coronary Drug Project: Clofibrate and niacin in Coronary Drug Project: Clofibrate and niacin in coronary heart disease. JAMA 1975;coronary heart disease. JAMA 1975;

8,341 males from 31-64 years old with history 8,341 males from 31-64 years old with history of MIof MI

Randomized to conjugated estrogens, Randomized to conjugated estrogens, clofibrate, dextrothyroxine, niacin (3000 clofibrate, dextrothyroxine, niacin (3000 mg/day), or placebomg/day), or placebo

Niacin had early reduction in rates of MI and a Niacin had early reduction in rates of MI and a mortality benefit that was maintained at 15-mortality benefit that was maintained at 15-year follow-up!year follow-up!

From JAMA 1975 and Canner et al. JACC 1986

Niacin, revisited…Niacin, revisited…

Niacin = Nicotinic acid = Vitamin B3Niacin = Nicotinic acid = Vitamin B3In high doses decreases LDL, increases HDLIn high doses decreases LDL, increases HDL

Most common side effects are flushing, itching, Most common side effects are flushing, itching, rashrash

Over-the-counter; relatively inexpensiveOver-the-counter; relatively inexpensive

Niacin extended-release tablets: available since Niacin extended-release tablets: available since 1997 (Niaspan) does reduce flushing rates1997 (Niaspan) does reduce flushing rates

NSAIDs 30 min before niacin and extended-release NSAIDs 30 min before niacin and extended-release niacin are shown to reduce flushingniacin are shown to reduce flushing

Niacin, revisited…Niacin, revisited…ARBITER 6-HALTSARBITER 6-HALTS

CAD patients with LDL < 100, HDL < 50-55CAD patients with LDL < 100, HDL < 50-55statin + extended-release niacin (2000 mg/day)statin + extended-release niacin (2000 mg/day) - versus -- versus -

statin + ezetimibestatin + ezetimibeLower LDL with ezetimibeLower LDL with ezetimibeHigher HDL and lower TG with niacinHigher HDL and lower TG with niacinBUT OUTCOMES. . .BUT OUTCOMES. . .

From Taylor et al. NEJM 2009

Is there any value to Is there any value to ezetimibe?ezetimibe?

Ezetimibe (Zetia)Ezetimibe (Zetia)Decreases Decreases intestinal intestinal absorption of absorption of cholesterolcholesterolEffective in Effective in reducing LDLreducing LDL

But, does not But, does not reduce plaque reduce plaque or clinical eventor clinical event

Probably only Probably only useful when useful when statins not statins not toleratatedtoleratated

Nutritional Nutritional supplement supplement

therapytherapySUPPLEMENT 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

SummarySummaryTreat CAD and CAD-equivalent patients to Treat CAD and CAD-equivalent patients to LDL goal < 70-100 LDL goal < 70-100

““Best statin”: atorvastatin and rosuvastatin Best statin”: atorvastatin and rosuvastatin have most recent data with pleotrophic have most recent data with pleotrophic effects and plaque stabilization/regressioneffects and plaque stabilization/regression

Niacin has important role in lipid Niacin has important role in lipid managementmanagement

Some quality nutritional supplement have Some quality nutritional supplement have valuevalue

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