Lipid Lowering Strategies

Transcription

1 Lipid Lowering Strategies Becky K. Captain, RN, MSN, CLS, BC, FNP-C Clinical Lipid Specialist Conflict of Interest Disclosure & Resolution Consultant for Good Things Health Speaker for Abbott and Forest Pharmaceuticals Objectives Know NCEP ATP III guidelines Know how to lower LDL through diet and medications Know how to lower non-hdl cholesterol adnt triglycerides through diet and medication

2 A Whole New World Cath Lab Sensation 16 MS CT

3 How Much of the Patient Are We Treating? m 2 1,000 m 2 70 KG Male = 1 / 5,000,000 Primary & Secondary Goals of Lipid Management According to NCEP LDL-C Primary target after TLC LDL-C C <100 mg/dl identified as optimal for pts. w/ CHD or CHD risk equivalent NCEP recommends optional LDL-C C goal of <70 mg/dl for high risk pts. Non-HDL HDL-C Secondary target if TG are mg/dl and LDL-C goal is met Non-HDL HDL-C C = Total Cholesterol minus HDL-C Non-HDL HDL-C C represents all atherogenic particles Non-HDL HDL-C C goal is 30mg/dL higher than LDL-C C goal Increasing HDL-C C will lower Non-HDL HDL-C NCEP ATP III Final Report, Circulation 2002;

4 Comparison of LDL Cholesterol and Non-HDL Cholesterol Goals Risk Category LDL-C Goal (mg/dl) Non-HDL-C Goal (mg/dl) CHD and CHD Risk Equivalent (10-year risk for CHD >20%) <100 (optional <70) <130 (optional <100) Multiple (2+) Risk Factors and 10-year risk <20% <130 (optional <100) <160 (optional <130) 0 1 Risk Factor <160 <190 NCEP ATP III Final Report, Circulation 2002; CHD Risk Equivalents >20% 10-year risk of CHD (Framingham projections) Diabetes Other forms of clinical atherosclerotic disease: Peripheral arterial disease Abdominal aortic aneurysm Carotid artery disease Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA 2001;285: Peripheral Arterial Disease (PAD) Studies of pts w/ PAD support the concept that PAD, regardless of diagnosis (ABI, lower limb blood flow studies, or clinical symptoms) is a CHD risk equivalent Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA 2001;285:

5 Abdominal Aortic Aneurysm (AAA) Study population: 300 men and 43 women (aged 45 89) operated on for AAA, separated into 4 groups based on preoperative CHD history and ECG Follow-up: 6 11 years Results: annual CHD mortality 1.9% in persons with no symptoms, no prior history of CHD, and normal ECG (31%) 2.0% in persons with no symptoms, but previous MI by ECG (33%) 3.9% in persons with angina/prior MI (30%) Because the rate of CHD events is at least twice that of CHD mortality, patients with no previous history of CHD events would fall into the CHD risk equivalent category Hertzer NR. Ann Surg 1980;192: Carotid Artery Disease: Asymptomatic Mayo Asymptomatic Carotid Atherosclerosis Study Subjects 158 patients, 40% with history of CAD, 15% diabetic Disease severity Asymptomatic stenosis 50% Trial stopped because of high MI and TIA event rate in surgical arm secondary to cessation of medical therapy (aspirin) CHD events After 2.5-year follow-up: 12 CHD events Estimated 10-year CHD event rate = 30% Executive Committee for the Asymptomatic Carotid Atherosclerosis Study. JAMA 1995;273: Incidence of MI during a 7-Year Follow-up in a Finnish Population Fatal or Nonfatal MI (%) 40 P< P< Prior MI No prior MI Prior MI No prior MI Nondiabetic subjects Diabetic subjects (n=1373) (n=1059) Haffner SM et al. N Engl J Med 1998;339:

6 Comparison of LDL Cholesterol and Non-HDL Cholesterol Goals Risk Category LDL-C Goal (mg/dl) Non-HDL-C Goal (mg/dl) CHD and CHD Risk Equivalent (10-year risk for CHD >20%) <100 (optional <70) <130 (optional <100) Multiple (2+) Risk Factors and 10-year risk <20% <130 (optional <100) <160 (optional <130) 0 1 Risk Factor <160 <190 NCEP ATP III Final Report, Circulation 2002; Major Risk Factors (exclusive of LDL) Cigarette Smoking Hypertension HDL < 40 mg/dl Family history of premature CHD First degree relative (male <55 yrs; female < 65 yrs) Age Men > 45 yrs Females > 55 yrs NCEP ATP III Final Report, Circulation 2002; More than 3 in 4 American adults have LDL-C levels of 100 mg/dl or higher LDL-C levels of all adults (United States) 29% Near or above optimal ( mg/dl) 24% Optimal (<100 mg/dl) 6% Very high ( 190 mg/dl) 76% 100 mg/dl 13% High ( mg/dl) 28% Borderline high ( mg/dl) Dyslipidemia is a leading risk factor for CHD the most prevalent form of CVD Unpublished data from the Third National Health and Nutrition Examination Survey (NHANES III), CDC 1994; data from Summary report, March Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (ATP III). JAMA. 2001;285:

7 N3-173 Global Risk Hazda Hunter-Gatherer Inuit Humans Ikung Pygmy San Mean Total Cholesterol (mg/dl (mg/dl)) Hazda 110 Inuit 140 Pygmy 100 San 120!Kung 120 Wild Primates Baboon Howler Monkey Night Monkey Mean Total Cholesterol (mg/dl (mg/dl)) Baboon 110 Howler Monkey 110 Night Monkey 140

8 Horse Mammals Boar Pig Black Rhinoceros African Elephant Horse Mean Total Cholesterol (mg/dl dl) Pig 100 Rhino 90 Elephant 110 Boar 70 Horse Mammals Boar Pig Black Rhinoceros African Elephant Adult American Horse Mean Total Cholesterol (mg/dl dl) Rhino 90 Elephant 110 Boar 70 Adult American ~ 209 How To Lower LDL Cholesterol Diet Decrease Saturated and Trans Fats Exercise Prescription Meds Supplements

9 How To Lower LDL - Prescriptions Statin Medications Cholesterol Absorption Inhibitor Bile acid sequestrant CHD Risk Reduction with Statin Therapy Relative Risk Reduction (%) Endpoints Major coronary events Coronary deaths Cardiovascular deaths Noncardiovascular events Total mortality Strokes Intermittent claudication Angina La Rosa JC et al. JAMA 1999;282: Crouse JR III et al. Arch Intern Med 1997;157: Pedersen TR et al. Am J Cardiol 1998;81: % Reduction in LDL-C Pharmacologic Therapy: Dose Response of Different Statins Response to Minimum/Maximum Statin Dose Fluvastatin 20/80 mg Pravastatin 20/80 mg Lovastatin 20/80 mg Simvastatin 20/80 mg Atorvastatin 10/80 mg LDL-C = low-density lipoprotein cholesterol Reprinted from Illingworth DR. Med Clin North Am. 2000;84:23 42, with permission from Elsevier Limited.

10 Pharmacologic Therapy: Dose Response of Different Statins 10 mg 20 mg 30 mg 40 mg 0% Atorvastatin Rosuvastatin Simvastatin Mean % Change in LDL-C from Untreated Baseline Value -10% 28-20% % % with -40% 6 14% with 3 titrations 3 titrations % 3 6* 9% with 3* 2 titrations -60% *P < vs. atorvastatin 10 mg and simvastatin 20 mg and 40 mg P = vs. atorvastatin 20 mg LDL C=low-density lipoprotein cholesterol Jones PH, et al. Am J Cardiol. 2003;92: Statins: Kidney Issues Assess renal function before initiating statin therapy Statin therapy may be used in patients with chronic kidney disease (some statins may need dose adjustments) No need to routinely monitor serum creatinine or proteinuria Reprinted from McKenney JM, et al. Am J Cardiol 2006; 97:89C 94C, with permission from Elsevier. NKF Recommendations for Statin Dose Adjustment in CKD Atorvastatin Pravastatin Simvastatin Lovastatin Fluvastatin Rosuvastatin Adjust for reduced GFR (ml/min/1.73 m 2 ) No adjustment No adjustment No adjustment No adjustment No adjustment No adjustment <30 <15 No adjustment No adjustment No adjustment No adjustment Starting dose 5 mg daily in patients with severe kidney disease Use doses >20 mg/day cautiously in patients with GFR <30 No dose adjustments needed for mild to moderate kidney disease; use caution in patients with severe kidney disease; fluvastatin not studied at doses >40 mg in these patients Starting dose 5 mg and NOT to exceed 10 mg in patients with GFR <30 30 National Kidney Foundation. Am J Kidney Dis. 2007;49(suppl 2):S1-S180.

11 Drug Drug Interaction Comparison Rosuvastatin Simvastatin simvastatin/ ezetimibe Atorvastatin Pravastatin & Fluvastatin Azole Fungal Agents, Macrolides, Protease No Inhibitors, Nefazadone, (Evaluate Risk-benefit) Avoid Avoid Grapefruit Juice (>1 Qt/Day) No No (Evaluate Risk-benefit) (Evaluate Risk-benefit) Fibrates (Max 10 mg) (Max 10 mg) Avoid No No (Evaluate Risk-benefit) (Evaluate Risk-benefit) Niacin >1 G/D No No No No No (Evaluate Risk-benefit) (Evaluate Risk-benefit) (Evaluate Risk-benefit) (Evaluate Risk-benefit) (Evaluate Risk-benefit) Cyclosporine (Max 5 mg) (Max 10 mg) (Max 10/10) No No (Evaluate Risk-benefit) (Evaluate Risk-benefit) Amiodarone/Verapamil Not Mentioned (Max 10 mg) (Max 10/10) No Effect Not Mentioned Warfarin Baseline INR 2 3 To >4 Baseline INR To Baseline INR To No Effect No Effect * Sasiela W, et al. Poster presented at: 52nd ACC Scientific Session. March 30, 2003-April 2, 2003; Chicago, Ill; Crestor (rosuvastatin) [package insert]. Wilmington, Del: AstraZeneca Pharmaceuticals LP; 2005; Lipitor (atorvastatin) [package insert]. New York, NY: Pfizer, Inc; 2003; Zocor (simvastatin) [package insert]. Whitehouse Station, NJ: Merck & Co; 2003; Vytorin (simvastatin/ezetimibe) [package insert]. North Wales, PA: MERCK/Schering-Plough Pharmaceuticals; 2006 Statins: Muscle Issues (Continued) The risk of myopathy increases with respect to: Age (>80 years; especially in women) Multisystem diseases (chronic renal failure, especially due to diabetes) Multiple medications Perioperative periods Grapefruit juice >1 quart/day Pasternak RC, et al. J Am Coll Cardiol. 2002;40: Statins: Muscle Issues (Continued) When rhabdomyolysis occurs: Stop statin therapy Provide intravenous hydration After recovery, weigh the risks and benefits of restarting statin therapy Reprinted from McKenney JM, et al. Am J Cardiol. 2006; 97:89C 94C, with permission from Elsevier.

12 Musculoskeletal AEs for Atorvastatin 80 mg Study MIRACL PROVE-IT REVERSAL ASAP ARBITER ALLIANCE AVERT TNT IDEAL Atorvastatin Dose Comparator 80 mg Placebo Duration Patient Population Patients on Atorvastatin Cases of 80 mg Rhabdomyolysis 16 weeks ACS mg Pravastatin 40 mg 2 years ACS mg Pravastatin 40 mg 18 months Established CHD mg Simvastatin 40 mg 2 years Heterozygous FH mg Pravastatin 40 mg 12 months ± CHD mg Usual Care 80 mg Angioplasty plus Usual Care 14,338 ~4 years Established CHD months Established CHD mg Atorvastatin 10 mg 4.9 years Established CHD * 80 mg Simvastatin 20/40 mg 4.8 years Established CHD Musculoskeletal AEs Simvastatin 40/80 mg Study A-to-Z * Not treatment-related. 9 cases of myopathy. Simvastati n Dose Simvastatin 40/80 mg Comparator Placebo/ Simvastatin 20 mg Duration Patient Population Patients on Simvastatin Cases of 40/80 mg Rhabdomyolysis 2 years ACS Muscle Safety: Simvastatin % of Patients with Myopathy/rhabdomyolysis 0.6% 0.5% 0.4% 0.3% 0.2% 0.1% 0.0% 0.53% 0.08% 0.02% 20 mg 40 mg 80 mg Vytorin (simvastatin/ezetimibe) [package insert]. North Wales, PA: MERCK/Schering-Plough Pharmaceuticals; Statins: Liver Issues Statins are well tolerated by most people Some people experience problems with liver function. Elevations in liver transaminases: Occur in 0.5% to 2.0% of statin users Are dose-dependent dependent Are usually reversed with a lowered statin dose Usually do not recur with rechallenge or use of another statin Rarely progress to liver failure Pasternak RC, et al. J Am Coll Cardiol. 2002;40:

13 Statins: Liver Issues (Continued) Modest increases* in liver transaminases are not a contraindication to: Initiate statins Continue statins Increase the dose of statins *Increases <3 the upper limits of normal. Pasternak RC, et al. J Am Coll Cardiol. 2002;40: McKenney JM, et al. Am J Cardiol. 2006;97:89C 94C. Statins: Liver Issues (Continued) When an elevation* in liver transaminases is isolated and asymptomatic: Repeat liver function tests If values are still high, rule out other causes Based on clinical judgment, consider: Continuing the statin Reducing the dose of the statin Discontinuing statin therapy *Increased <3 the upper limits of normal. Reprinted from McKenney JM, et al. Am J Cardiol. 2006; 97:89C 94C, with permission from Elsevier. Liver Effects: Ezetimibe Added to Simvastatin Increases LFTs 4% 3.6% % of Patients with LFT Abnormalities 3% 2% 1% 0.4% 1.3% 1.0% 1.8% 2.1% 0% Statin Alone Statin + Eze Simva Simva/Eze Overall Overall Simva 80 Simva/Eze 10/80 Zetia (ezetimibe) [prescribing information]: North Wales, PA Merck/Schering-Plough Pharmaceuticals North Wales, PA; Vytorin (simvastatin/ezetimibe) [package insert]. North Wales, PA: MERCK/Schering-Plough Pharmaceuticals; 2006; Zocor (simvastatin) [package insert]. Whitehouse Station, NJ: Merck & Co; 2003;

14 Liver Effects: Atorvastatin Clinically Relevant Transaminase Elevations 1.2% 0.9% Patients (%) 0.8% 0.4% 0.3% 0.4% 0.1% 0.1% 0.0% Placebo (n=1789) 10 mg (n=6093) 20 mg (n=2542) 40 mg (n=1983) 80 mg (n=3131) Atorvastatin Based on a patient population that experienced ALT/AST >3 x ULN on 2 consecutive occasions more than 14 days apart, or other defined criteria Across all doses, 0.5% of atorvastatin patients experienced elevated ALT/AST Newman CB, et al. Am J Cardiol. 2003;92: Statins: Liver Issues (Continued) Patients with these conditions may receive statins: Chronic liver disease Nonalcoholic fatty liver disease Nonalcoholic steatohepatitis Reprinted from McKenney JM, et al. Am J Cardiol. 2006;97: 89C 94C, with permission from Elsevier. Pasternak RC, et al. J Am Coll Cardiol. 2002;40: Statins: Monitoring (Continued) Lipid Panel Baseline 6 weeks 3 months Every 6 months Baseline Liver Function Tests 12 weeks after starting/increasing therapy Annually, as needed (when the patient reports liver symptoms) Baseline Creatine Kinase Test As needed (when patient reports muscle soreness, tenderness, or pain) Pasternak RC, et al. J Am Coll Cardiol. 2002;40: McKenney JM, et al. Am J Cardiol. 2006;97:89C 94C.

15 Bile Acid Sequestrants Bile Acid Sequestrants Colesevelam Indicated to lower LDL Improve glycemic control in adults w/ Type II DM Colestipol Cholestyramine» Colesevelam package insert Bile Acid Sequestrants: Colesevelam and Statins Colesevelam HCl 2300 mg (~4 tablets) 2300 mg (~4 tablets) 3750 mg (6 tablets) 3750 mg (6 tablets) Statin Lovastatin 10 mg Simvastatin 20 mg Simvastatin 10 mg Atorvastatin 10 mg TC* LDL-C* (%) (%) HDL-C* TG* (%) (%) 7 12 to 10 3 to 1 8 to * Change versus statin alone. Bays H et al. Expert Opin Pharmacother 2003;4: Davidson MH et al. Expert Opin Investig Drugs 2000;9:

16 Bile Acid Sequestrants Contraindications: Bowel Obstruction, hx of TG > 500 mg/dl dl, hx of hypertriglyceridemia induced pancreatitis Side Effects: GI: constipation, flatulence, bloating, nausea Careful: Reduces GI absorption of some drugs & vitamins. Recommended to be administered at least 4 hrs apart Ezetimibe: : Efficacy Added On to Ongoing Statin Therapy Patients on ongoing stable statin therapy* not reaching NCEP ATPII LDL-C C goal R A N D O M I Z A T I O N Open-label statin + ezetimibe (n=379, mean LDL-C C = 138 mg/dl) Open-label statin + placebo (n=390, mean LDL-C C = 139 mg/dl) Week < *40% on atorvastatin (weighted mean baseline dose 34 mg); 31% simvastatin (37 mg), and 29% others combined (pravastatin 29 mg, fluvastatin 35 mg, lovastatin 26 mg, and cerivastatin 0.4 mg) Gagné C et. al. Am J Cardiol 2002;90: Ezetimibe: Efficacy: "Add On" Study Reduction from baseline at week 8 (%) LDL-C * HDL-C *p<0.001 p<0.05 p< TG 14.0 Statin + placebo (n=390) Statin + ezetimibe 10 mg (n=379) Reprinted from Gagné C et al. Am J Cardiol 2002; 90: , with permission from Elsevier.

17 Plant Sterols/Stanols: Efficacy in Lowering LDL-C Maximum dose: 2 g/d Meta-analysis analysis results: LDL-C C lowering about 9 13% 9 Lowering greater in elderly: Additive to statin therapy Used in various population groups Well-tolerated Law M et al. BMJ 2000;320: Lichtenstein AH et al. Circulation 201;103: Case Study Patient Profile: White Female, 44 y.o. Occupation: Social Habits: Exercise: Concomitant Med. Cond.: Real Estate Agent Never Smoked rare ETOH Runs 20 miles weekly Dyslipidemia, No Known History of CAD Case Study cont d Current Meds: Omega 3 Fish Oils 1500 mg QD, MTV, Calcium Supplement w/ Vitamin D Allergies: NKDA Family History: Father died of MI age 50 Mother w/ CAD age 60 Exam: BMI 22.0, BP 110/70 mmhg HR 58. Pt. denies myalgias.

18 Case Study cont d Lab Values: TC 225; HDL 52; LDL 160; Trigs 65; Ratio 4.3; FBS 82 CPK 180 CR 1.0 ALT 15; AST 12 What would you do? Case Study cont d Would you recommend: Statin Nicotinic Acid Bile Acid Resin Fibrate Lifestyle modifications Calcium Score hscrp Other Supplements? Case Study cont d CardioScan: (+) CAD (Agatston( Score 225 with normal nuclear study) hs CRP: 2.1 Recommendations?

19 Case Study cont d Added Rosuvastatin 20 mg, ASA 81 mg 8 weeks later: TC 140 HDL 54 LDL 75 Trigs 54 Ratio 2.8 hs CRP 0.5 Initial Labs: TC 225 HDL 52 LDL 160 Trigs 65 Ratio 4.3 hscrp 2.1 Limitations of Statin Monotherapy on CHD Events Trial 4S WOSCOPS CARE AFCAPS LIPID HPS Drug Simvastatin Pravastatin Pravastatin Lovastatin Pravastatin Simvastatin N 30,817 20,586 Events,* n Control Group 2,042 1,212 Statin Group 1, Risk Reduction, % Events not Avoided, % PROSPER Pravastatin 5, ASCOT- LLA Total Atorvastatin 10,305 67, , , * Nonfatal MI and CHD death; AFCAPS also included unstable angina Weighted average Bays H. Expert Rev Cardiovasc Ther 2004;2: Treatment of Mixed Hyperlipidemia High LDL-C C and TGs Therapeutic Lifestyle Change Drug Therapy STEP 1 Achieve the LDL-C C goal STEP 2 Achieve the non-hdl HDL-C C goal Increase LDL-C C lowering or Add a niacin, fibrate or fish oils Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA 2001;285:

20 LRC Follow-up Study: CVD Mortality by Non-HDL-C and LDL-C in Men Non-HDL-C (mg/dl)ii Rate/ 10,000 < to < to < LDL-C (mg/dl) < to < to < RR with 95% CI LRC = Lipid Research Clinics; RR = Relative risk; CI = confidence interval. Cui Y et al. Arch Intern Med 2001;161: LRC Follow-up Study: CVD Mortality by Non-HDL-C and LDL-C in Women Non-HDL-C (mg/dl) Rate/ 10,000 < to < to < LDL-C (mg/dl) < to < to < RR with 95% CI LRC = Lipid Research Clinics; RR = Relative risk; CI = confidence interval. Cui Y et al. Arch Intern Med 2001;161: The Tricks with Trigs

21 Triglyceride Reduction Counsel on Diet (Limit or cut out simple carbs/simple sugars on a daily basis) Start or Increase Exercise min of aerobic activity 4 x week Omega 3 Fish Oil grams daily Return visit weeks Statin / Fish Oil Niaspan/IR Niacin Fibrates AHA Recommendations for Omega-3 FA Intake Population Patients without documented CHD Patients with documented CHD Patients needing triglyceride lowering Recommendation Eat a variety of (preferably oily) fish at least twice a week. Include oils and foods rich in α-linolenic acid (flaxseed, canola, and soybean oils; flaxseeds; and walnuts) Consume ~1 g of EPA+DHA per day, preferably from oily fish. EPA+DHA supplements could be considered in consultation with the physician 2 4 grams of EPA+DHA per day provided as capsules under a physician s care Kris-Etherton PM et al. Circulation 2002;106:

22 Fish Oils and Statins Marine fish oils rich in omega-3 3 fatty acids triglyceride levels & may be effective in combination w/ statins to treat pts w/ combined hyperlipidemia Fish oils plus statin may often be an alternative to fibrate plus statin Fish oils may have other CV effects complementary to those of statins,, such as: Reduction in malignant ventricular dysrhythmias Increased heart rate variability Antithrombotic effects Improved endothelial reactivity/relaxation Anti-inflammatory inflammatory effects Slight lowering of blood pressure Bays HE et al. Expert Opin Pharmacother 2003;4: Kris-Etherton PM et al. Circulation 2002;106: VA-HIT: Treating Dyslipidemia Beyond LDL-C Improves Clinical Outcomes % Change (Gemfibrozil vs Placebo) * -31* -22* LDL-C HDL-C TG Nonfatal CHD Stroke MI or Death CHD Death VA-HIT = Veterans Affairs High-Density Lipoprotein Intervention Trial. *p p = Investigator-designated men with CHD, HDL 40 mg/dl, and LDL 140 mg/dl were randomized to gemfibrozil (1200 mg/d) or placebo, and followed for a median of 5.1 years. Rubins HB et al. N Engl J Med. 1999;341: * Percent Change Statin + Fibrate % Simva + Gemfibrozil 50% 16% HDL-C 38 LDL-C TG Prava/Simva + Fenofibrate 166 LDL-C 28% 191 TG 41% Da Col PG et al. Curr Ther Res Clin Exp 1973;53: Ellen RL et al. Am J Cardiol 1998;81:60B-65B. 22% HDL-C 34

23 ACCORD Study Design Overall ACCORD Glycemia Trial: 10,251 participants Lipid Trial: 5,518 in Lipid Trial 2765 randomized to fenofibrate 2753 randomized to placebo Primary Outcome: First occurrence of a major cardiovascular event (nonfatal MI, nonfatal stroke, cardiovascular death) 87% power to detect a 20% reduction in event rate, assuming placebo rate of 2.4%/yr and 5.6 yrs follow-up in participants without events. Conclusion The combination of fenofibrate & simvastatin did not reduce the rate of fatal CV events, nonfatal MI, or nonfatal stroke, as compared w/ simvastatin alone. These results do not support the routine use of combination therapy w/ fenofibrate & simvastatin to reduce CV risk in the majority of high-risk pts w/ type 2 diabetes. Drug Drug Interaction Comparison Rosuvastatin Simvastatin simvastatin/ ezetimibe Atorvastatin Pravastatin & Fluvastatin Azole Fungal Agents, Macrolides, Protease No Inhibitors, Nefazadone, (Evaluate Risk-benefit) Avoid Avoid Grapefruit Juice (>1 Qt/Day) No No (Evaluate Risk-benefit) (Evaluate Risk-benefit) Fibrates (Max 10 mg) (Max 10 mg) Avoid No No (Evaluate Risk-benefit) (Evaluate Risk-benefit) Niacin >1 G/D No No No No No (Evaluate Risk-benefit) (Evaluate Risk-benefit) (Evaluate Risk-benefit) (Evaluate Risk-benefit) (Evaluate Risk-benefit) Cyclosporine (Max 5 mg) (Max 10 mg) (Max 10/10) No No (Evaluate Risk-benefit) (Evaluate Risk-benefit) Amiodarone/Verapamil Not Mentioned (Max 10 mg) (Max 10/10) No Effect Not Mentioned Warfarin Baseline INR 2 3 To >4 Baseline INR To Baseline INR To No Effect No Effect * Sasiela W, et al. Poster presented at: 52nd ACC Scientific Session. March 30, 2003-April 2, 2003; Chicago, Ill; Crestor (rosuvastatin) [package insert]. Wilmington, Del: AstraZeneca Pharmaceuticals LP; 2005; Lipitor (atorvastatin) [package insert]. New York, NY: Pfizer, Inc; 2003; Zocor (simvastatin) [package insert]. Whitehouse Station, NJ: Merck & Co; 2003; Vytorin (simvastatin/ezetimibe) [package insert]. North Wales, PA: MERCK/Schering-Plough Pharmaceuticals; 2006

24 HDL Cholesterol Classification of Serum HDL-C Levels HDL-C Category ATP II Levels ATP III Levels Low HDL-C <35 mg/dl <40 mg/dl High HDL-C 60 mg/dl 60 mg/dl Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA 1993;269: Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA 2001;285: Coronary Drug Project: Macrovascular Outcomes* 15% Reduction 35 P<.05 Placebo (n = 2789) Niacin (n = 1119) 30 Event Rate, % % Reduction P<.05 24% Reduction P<.05 47% Reduction P< CHD Death/ Nonfatal MI Nonfatal MI *Total follow-up experience (mean, 6.2 yrs) 5-year incidence TIA, transient ischemic attack Stroke/TIA CV Surgery CDP Research Group. JAMA. 1975;231:

25 HDL-Atherosclerosis Treatment Study (HATS) Niacin and Statin Outcome Trial Composite Event Rate, % Placebo 89% Reduction * S + N AV *P<.05 vs Placebo 14.3 S + N + AV Coronary Death, MI, Stroke, or Revascularization Brown BG et al. N Engl J Med 2001;345: Familial Atherosclerosis Treatment Study (FATS): 10-Year Follow-up Results Usual Care (n=101) Triple Therapy (n=75) Event Rate (%) * p< * 5.3* Deaths CV Events LDL-C mg/dl; HDL-C mg/dl ; TG mg/dl LDL-C mg/dl; HDL-C mg/dl; TG mg/dl Brown BG et al. Circulation 1998;98:I-635. AIM HIGH Atherothrombosis Intervention in Metabolic Syndrome w/low HDL-c/High Triglyceride & Impact on Global Health Outcomes Randomized trial of niacin vs. placebo in the background of Simvastatin therapy in ~3,300 people w/ CVD, low HDL, and high triglycerides Stopped early due to lack of futility w/ about 2/3 of the events having occurred. HDL s were higher and TG levels lower in the niacin group with LDL levels very low and equal in the two groups There were more ischemic strokes in the niacin group.

26 Angiographic Effects of Lipid Drug Classes Meta-Analysis, 12 Trials 4 Change from Baseline in Mean Proximal % Stenosis (Δ%S) Progression Regression Placebo (6) Fibrates (1) Statins (6) Statin+Resin (1) Niacin Combos (4) % Change in LDL-C in Rx (%Δ) Placebo-Adjusted Brown BG, Curr Opin Lipidol. 2006;17: Objectives Know NCEP ATP III guidelines Know how to lower LDL through diet and medications Know how to lower non-hdl cholesterol adnt triglycerides through diet and medication

27 Questions Thank You