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1、Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA 2001;285:2486-2497.Risk CategoryLDL-C GoalConsider Drug TherapyCHD or CHD risk equivalent100 mg/dL 130 mg/dL*2 Risk Factors 10-yr risk 1020% 10-yr risk 10%130 mg/dL130 mg/dL130 mg/dL160 mg/dL2 Risk Factors

2、160 mg/dL190 mg/dL* 100129 mg/dL = after TLC, consider statin, niacin, or fibrate therapyExpert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA 2001;285:2486-2497.LDLPhysicians Desk Reference. 55th ed. Montvale, NJ: Medical Economics, 2001.DailyDoseAtorvaFluva

3、LovaPravaSimva10 mg39%22%30%20 mg43%22%27%32%38%40 mg50%25%32%34%41%80 mg60%36%42% 47%Stein EA et al. Am J Cardiol 1998;81:66B-69B. Lova 20 mg1%9%32% Prava 10 mg6%11%22% Simva 10 mg1%20%28%*Nonfatal MI or CHD death; *ischemic eventsDowns JR et al. JAMA 1998;279:1615-1622. | Shepherd J et al. N Engl

4、J Med 1999;333:1301-1307. | Scandinavian Simvastatin Study Group. Lancet 1994;344:3-9. | Sacks FM et al. N Engl J Med 1996;335:1001-1009. | LIPID Study Group. N Engl J Med 1998;339:1349-7. | Schwartz GG et al. JAMA 2001;285:1711-1718. | Pitt B et al. N Engl J Med 1999;341:70-76.Trial DrugCHD Risk Re

5、ductionPrimary Prevention AFCAPS/TexCAPS Lovastatin40%* WOSCOPS Pravastatin31%*Secondary Prevention 4S Simvastatin34%* CARE Pravastatin24%* LIPID Pravastatin24%*Ischemia MIRACL Atorvastatin26%* AVERT Atorvastatin36%*La Rosa JC et al. JAMA 1999;282:2340-2346. | Crouse JR III et al. Arch Intern Med 19

6、97;157:1305-1310. | Pedersen TR et al. Am J Cardiol 1998;81:333-335.+203530250 5 101520404550Major coronary eventsCoronary deathsCardiovascular deathsNoncardiovascular eventsTotal mortalityStrokesIntermittent claudicationAngina* Time course establishednCommon side effectsnHeadache Myalgia FatiguenGI

7、 intolerance Flu-like symptomsnIncrease in liver enzymesnOccurs in 0.5 to 2.5% of cases in dose-dependent mannernSerious liver problems are exceedingly rarenManage by reducing statin dose or discontinue until levels return to normalnMyopathynOccurs in 0.2 to 0.4% of patientsnRare cases of rhabdomyol

8、ysisnReduce bynCautiously using statins in patients with impaired renal functionnUsing the lowest effective dosenCautiously combining statins with fibratesnAvoiding drug interactionsnCareful monitoring of symptomsnPresence of muscle toxicity requires the discontinuation of the statin-20%-15%-10%-5%0

9、%Davidson MH et al. Expert Opin Investig Drugs 2000;9:2663-2671.Reprinted with permission from Ashley Publications.VLDLVLDLLDLAdapted from Knopp RH. N Engl J Med 1999;341:498-511.1999 Massachusetts Medical Society. All rights reserved.0 1 g/d 2 g/d 3 g/dBaseline-15%12.5%25%-30%35%Expert Panel on Det

10、ection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA 2001;285:2486-2497.-50%-40%-30%-20%-10%0%Knapp HH et al. Am J Med 2001;110:352-360.Reprinted with permission from Excerpta Medica Inc.-30%-20%-10%0%10%20%30%-40%-30%-20%-10%0%10%20%30%Wolfe ML et al. Am J Cardiol 2001;87:476

11、-479.Brown BG et al. Am J Cardiol 1997;80:111-115.Baseline (mg/dL)8 months (mg/dL)Change (%) LDL-C2158560% HDL-C4652 13% LDL-C/HDL-C ratio4.81.765%Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA 2001;285:2486-2497.Patient CategoryLDL-C target (mg/dL)Non

12、-HDL-C target (mg/dL) No CHD, 2 RF160190 No CHD, 2+ RF130160 CHD or CHD risk equivalent100130Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA 2001;285:2486-2497.-50-40-30-20-1001020Ballantyne CM et al. Am J Cardiol 2001;88:265-269.Atorvastatin(n=1,888)Fl

13、uvastatin(n=474)Lovastatin(n=472)Pravastatin(n=461)Simvastatin(n=462)LDL-CNon-HDL-CDavignon J et al. Am J Cardiol 1994;73:339-345.-50-40-30-20-1001020Indications: Adjunctive therapy to dietHypertriglyceridemia (Type IV and V)With statins or other LDL-Clowering drugs in mixed hyperlipidemia Efficacy:

14、 Decrease TG 3040%LDL-C remains the same or increasesNo change in HDL-CSide Effects: GI upset and a “fish burp”Intervention Trials:Lyon Heart Study (dietary), GISSI Prevenzione Trial, othersIndications:Adjunctive therapy to dietHypertriglyceridemia (Type IV and V)Combined hyperlipidemia (Type IIb) w

15、ith low HDL-C who do not respond to nicotinic acidMechanism of Action:Increase peripheral lipolysis and decrease hepatic TG productionEfficacy:Decrease TG 2550%LDL-C decreases, remains the same, or increasesIncrease HDL-C 1525% in hypertriglyceridemiaSide Effects:GI upset (8%), cholelithiasis, myosi

16、tis, abn LFTsContraindications:Hepatic or renal dysfunctionPre-existing gallbladder diseaseIntervention Trials:HHS, VA-HIT, BIP, LOCAT, BECAIT, DAISHypercholesterolemia (%)Mixed HPL (%)Fenon=92Plbn=88 Feno n=24 Plb n=22Total Cholesterol17.50.415.8+4.6LDL-C20.3+0.46.10.5HDL-C +11.11.2+15.33.5Total Tr

17、iglycerides37.94.244.6+22.3LDL-C/HDL-C 27.11.913.3 0.0VLDL-C38.42.552.7+8.4p0.10Brown WV et al. Arteriosclerosis 1986;6:670-678.1999 Lippincott Williams & Wilkins. lww Frick MH et al. N Engl J Med 1987;317:1237-1245. | Manninen V et al. Circulation 1992;85:37-45. | BIP Study Group. Circulation 2000;102:21-27. | Rubins HB et al. N Engl J Med 1999;341:410-418.* Post hoc analysis of subgroup with TG 200 mg/dL and HDL-C 42 mg/dL.* Post hoc analysis of subgroup with TG 200 mg/dL and HDL-C 35