Dyslipidemia. Hisham Aljadhey, PharmD, PhD

Transcription

1 Dyslipidemia Hisham Aljadhey, PharmD, PhD

2 Etiology Primary hyperlipidemia Familial hypercholesterolemia Secondary hyperlipidemia Disease states: hypothyroidism, nephrotic syndrome, obesity, DM, alcoholism Drugs: thiazides, B-blockers, isotretinoin, prednisone, progestins, estrogens, protease inhibitors, anabolic steroids, cyclosporine

3 Diagnosis Check fasting lipoprotein profile (9-12 hours of fasting) Screening: Every 5 yrs. in patients > 20yo Other method Non-fasting total cholesterol and HDL

4 Benefits of Treating Hyperlipidemia Lowering LDL & TG, Raising HDL will reduce: Mortality, Coronary events including MI, Stroke

5 National Cholesterol Education Program (NCEP) Reports Adult Treatment Panel (ATP) I: 1988 Adult Treatment Panel (ATP) II: 1993 Adult Treatment Panel III (ATP) III: 2001 Update to the ATP III (2004) terol/index.htm

6 Step 1: Determine lipoprotein levels

7 ATP III Lipid and Lipoprotein Classification Total Cholesterol (mg/dl) <200 Desirable Borderline high 240 High

8 ATP III Lipid and Lipoprotein Classification LDL Cholesterol (mg/dl) <100 Optimal Near optimal/above optimal Borderline high High 190 Very high

9 ATP III Lipid and Lipoprotein Classification (continued) HDL Cholesterol (mg/dl) <40 Low 60 High

10 ATP III Lipid and Lipoprotein Classification (continued) Triglycerides (mg/dl) < Normal Borderline high High Very high

11 Assessment If total cholesterol <200mg/dL and HDL >40mg/dL. No follow-up for patients without CHD and <2 risk factors.

12 Step 2: Identify presence of CHD or CHD risk equivalents

13 CHD and CHD Risk Equivalents Established CHD Other clinical forms of atherosclerotic disease (peripheral arterial disease, abdominal aortic aneurysm, and symptomatic carotid artery disease) Diabetes Multiple risk factors that confer a 10-year risk for CHD >20%

14 Step 3: Determine presence of major risk factors (other than LDL)

15 Major Risk Factors Cigarette smoking Hypertension (BP 140/90 mmhg or on antihypertensive medication) Low HDL cholesterol (<40 mg/dl) Family history of premature CHD CHD in male first degree relative <55yrs CHD in female first degree relative <65yrs Age (men 45 years; women 55 years) HDL cholesterol 60 mg/dl counts as a negative risk factor; its presence removes one risk factor from the total count.

16 Step 4: Assess 10-year CHD risk if 2+ risk factors For patients with multiple (2+) risk factors Use Framingham risk tables to perform 10- year risk assessment For patients with 0 1 risk factor 10 year risk assessment not required Most patients have 10-year risk <10%

17 Framingham Risk Tables

18

19 Step 5: Determine risk category: LDL Cholesterol Goals Risk Category LDL-C Goal Initiate TLC Consider Drug Therapy High risk: CHD or CHD Risk Equivalents (10-year risk >20%) Moderately high risk: 2+ Risk Factors (10-year risk 10-20%) Moderate risk: 2+ Risk Factors (10-year risk <10%) Lower risk: 0 1 Risk Factor < 100mg/dL (optional < 70mg/dL) < 130mg/dL (optional < 100mg/dL) > 100mg/dL > 100mg/dL (<100mg/dL: consider drug options) > 130mg/dL > 130mg/dL ( mg/dL: consider drug options) < 130mg/dL > 130mg/dL > 160mg/dL < 160mg/dL > 160mg/dL > 190mg/dL ( mg/dL: LDL-lowering drug optional)

20 Step 6: Initiate therapeutic lifestyle changes (TLC)

21 Therapeutic Lifestyle Changes (TLC) in LDL-Lowering Therapy Major Features TLC Diet Reduced intake of cholesterol-raising nutrients: Saturated fats <7% of total calories Dietary cholesterol <200 mg per day LDL-lowering therapeutic options Plant stanols/sterols (2 g per day) Viscous (soluble) fiber (10 25 g per day) Weight reduction Increased physical activity

22 Step 7: Consider adding drug therapy if LDL is above goal

23 Drug Therapy Drug therapy should decrease LDL levels by 30-40% in high-risk and moderately high-risk pts. For patients hospitalized for coronary events or procedures Measure LDL within 24 hours Discharge on LDL-lowering drug if LDL-C 70 Start lifestyle therapies simultaneously with drug

24 Therapeutic Options Statins Bile acid sequestrants Cholesterol absorption inhibitors Nicotinic acid Fibric acids

25 Drug Effects on the Lipid Profile Drug LDL HDL TG Statins % % % Bile acid sequestrants % + 3-5% % Ezetimibe - 17% + 1.3% - 6% Nicotinic acid % % % Fibric acids % (nl TG) +10% (high TG) % %

26 HMG CoA Reductase Inhibitors (Statins) Statin Lovastatin (Mevacor R ) Pravastatin (Pravachol R ) Simvastatin (Zocor R ) Fluvastatin (Lescol R ) Atorvastatin (Lipitor R ) Rosuvastatin (Crestor R ) Dose Range mg mg mg mg mg 5 40 mg

27 HMG CoA Reductase Inhibitors (Statins) (continued) Demonstrated Therapeutic Benefits Reduce major coronary events Reduce CHD mortality Reduce coronary procedures (PTCA/CABG) Reduce stroke Reduce total mortality

28 Comparison of Statins Lovastatin Pravastatin Simvastatin Fluvastatin Atorvastatin Rosuvastatin (Mevacor R ) (Pravachol R ) (Zocor R ) (Lescol R ) (Lipitor R ) (Crestor R ) Doseresponse LDL Reduction 20mg: 29% 40mg: 31% 80mg: 48% 10mg: 19% 20mg: 24% 40mg: 34% 10mg: 28% 20mg: 35% 40mg: 40% 80mg: 48% 20mg: 17% 40mg: 25% 80mg: 35% 10mg: 38% 20mg: 46% 40mg: 51% 80mg: 54% 5mg: 41% 10mg: 48% 20mg: 55% 40mg: 62% Metabolism CYP3A4 Sulfation CYP3A4 CYP2C9 CYP3A4 Not signif.

29 HMG CoA Reductase Inhibitors (Statins) (continued) Major side effects Myopathy, Rhabdomyolysis Increased liver enzymes Cautions: Liver disease Drug interactions: Amiodarone, verapamil, diltiazem, itraconazole, fluconazole, erythromycin, clarithromycin,, nefazodone, fluvoxamine,, grapefruit juice: significantly increase levels of lovastatin and simvastatin and slightly increase levels of atorvastatin Cyclosporine and gemfibrozil increase level of all statins

30 Monitoring HMG CoA Reductase Inhibitors (Statins) (continued) Myalgia- baseline, 6-12 weeks after initiation, and at each follow-up visit CK- baseline and prn muscle symptoms LFTs- baseline and 6-12 weeks after initiation or dosage increase, then periodically and/or prn symptoms

31 Bile Acid Sequestrants Drug Range Cholestyramine Colestipol Dose 4 16 g 5 20 g Colesevelam g

32 Bile Acid Sequestrants (continued) Side effects GI distress/constipation Contraindications Elevated TG (especially >400 mg/dl) Drug interactions Colesevelam does not decrease absorption of other drugs Cholestyramine and colestipol decrease absorption of other drugs

33 Cholesterol Absorption Inhibitors Ezetimibe: 10mg QD Reduces LDL-C and TG Increases HDL-C Synergistic with statin Combination more effective than increasing statin dose

34 Side effects Cholesterol Absorption Inhibitors (continued) Abdominal pain, diarrhea, arthralgia, back pain Inc. LFTs when administered with a statin Contraindications Moderate to severe hepatic impairment

35 Nicotinic Acid Drug Form Range Immediate release (crystalline) Extended release Sustained release Dose g 1 2 g 1 2 g

36 Side effects Nicotinic Acid (continued) flushing, hyperglycemia, hyperuricemia, upper GI distress, hepatotoxicity, myositis/rhabdomyolysis Contraindications/cautions liver disease, severe gout, peptic ulcer Monitoring LFTs (baseline and q 6-12 wks x 1 yr, then periodically and/or prn symptoms) uric acid, glucose, GI adverse effects, flushing, CPK prn symptoms

37 Fibric Acids Drug Gemfibrozil Fenofibrate Dose 600 mg BID 200 mg QD

38 Fibric Acids (continued) Side effects dyspepsia, gallstones, myopathy Contraindications Severe renal or hepatic disease Drug interactions Fenofibrate does not inhibit statin metabolism and is less likely to increase risk of rhabdomyolysis Monitoring LFTs periodically, CPK prn symptoms

39 Omega-3 fatty acids (Fish oil) Drug Dose Range Omacor 4gm QD Decreases TG by 20-50% Reduce MI, stroke, and total mortality

40 Step 8: Identify metabolic syndrome and treat after 3 month of TLC

41 Clinical Identification Diagnosis requires 3 or more of the following risk factors: Abdominal obesity: M waist >40 in., F waist >35 in. Triglycerides >150mg/dL Low HDL: M <40mg/dL, F <50mg/dL Blood pressure: >130/>85 mmhg Fasting glucose: >110mg/dL

42 Treatment of Metabolic Syndrome Treat underlying causes Overweight and obesity Physical inactivity

43 Treatment of Metabolic Syndrome Treat associated lipid and non-lipid risk factors Hypertension Prothrombotic state- use low-dose ASA for CHD patients Atherogenic dyslipidemia (lipid triad)- treat elevated TG and/or low HDL TLC x 3mo. Consider drug therapy if lipid control still suboptimal

44 Step 9: Treat elevated triglycerides

45 Classification of Serum Triglycerides Normal Borderline high High Very high <150 mg/dl mg/dl mg/dl 500 mg/dl

46 Causes of Elevated Triglycerides Obesity and overweight Physical inactivity Smoking, excess alcohol intake High carbohydrate diets (>60% of energy intake) Diseases (type 2 diabetes, chronic renal failure) Various genetic dyslipidemias

47 Treatment Primary target is LDL Intensify weight management Increase physical activity If a high risk pt has high TG or low HDL-C, may consider adding a fibrate or nicotinic acid to LDL-lowering drug If TG are >200mg/dL after LDL goal is reached, determine non-hdl goal

48 Non-HDL Cholesterol Non-HDL cholesterol = VLDL + LDL cholesterol = (Total Cholesterol HDL cholesterol) VLDL cholesterol: denotes atherogenic remnant lipoproteins Non-HDL cholesterol: secondary target of therapy when serum triglycerides are 200 mg/dl (esp mg/dl) Non-HDL cholesterol goal:

49 Comparison of LDL & Non-HDL Cholesterol Goals Risk Category LDL-C Goal Non-HDL-C Goal High risk: CHD or CHD Risk Equivalents (10-year risk >20%) < 100mg/dL (optional < 70mg/dL) < 130mg/dL (optional < 100mg/dL) Moderately high risk: 2+ Risk Factors (10-year risk 10-20%) Moderate risk: 2+ Risk Factors (10-year risk <10%) Lower risk: 0 1 Risk Factor < 130mg/dL < 160mg/dL (optional < 100mg/dL) (optional < 130mg/dL) < 130mg/dL < 160mg/dL < 160mg/dL < 190mg/dL

50 Treatment (continued) Management of High Triglycerides ( mg/dl) If TG remain elevated after LDL goal is reached: Intensify therapy with lipid-lowering drug Add nicotinic acid or fibrate to lower VLDL

51 Treatment (continued) Management of Very High Triglycerides ( 500 mg/dl) Reduce triglycerides before LDL lowering Goal of therapy: prevent acute pancreatitis Very low fat diets ( 15% of caloric intake) Triglyceride-lowering drug usually required (fibrate or nicotinic acid)

52 Causes of Low HDL Cholesterol Elevated triglycerides Overweight and obesity Physical inactivity Type 2 diabetes Cigarette smoking Very high carbohydrate intakes (>60% energy) Certain drugs (beta-blockers, anabolic steroids, progestational agents)

53 Treatment of Low HDL Cholesterol Reach LDL goal first Implement weight reduction and increased physical activity (if the metabolic syndrome is present) If TG are 200 mg/dl, achieve non-hdl goal If TG are <200 mg/dl (isolated low HDL), consider nicotinic acid or fibrates for patients with CHD or CHD risk equivalents Increase physical activity Smoking cessation

54 Place in Therapy Statins: high LDL Bile acid sequestrants: young, not high TG Ezetimibe: high LDL, combined with statin Nicotinic acid: high TG and/or high LDL Fibric acids: high TG Combination therapy: statin and ezetimibe, statin and bile acid sequestrant, statin and nicotinic acid, statin and fibric acid

55 Monitoring and Follow-up Recheck fasting lipid profile in 4-6 weeks after starting drug therapy