25 Elderly People are the Major Target for Risk Reduction to Prevent Atherosclerotic Disease 동맥경화의정도 증상 (+) 증상 (-) 뇌졸중심근경색 위험인자 Hypercholesterolemia Hypertension Diabetes Mellitus Smoking Others 심장질환의고위험군이란? 심혈관질환자 특히급성관동맥증후군 당뇨환자 동맥경화성혈관질환자 매우심한정도의위험인자를가진경우 많은위험인자를가진경우 ; 3 개이상의위험인자를가진경우 중등도의위험을가지고있으면서대사성증후군또는높은 CRP 수치등을가진경우 (optional) 1 2 3 5 6 7 8 연령 ( 세 )
25 NCEP-III Guideline Major Risk Factors That Modify LDL Goals * (Exclusive of LDL Cholesterol) Cigarette smoking Hypertension (blood pressure 1/9 mmhg or on antihypertensive medication) Low HDL cholesterol (< /dl) Family history of premature CHD (CHD in male first-degree relative < 55 years ; CHD in female first-degree relative < 65 years) Age (men 5 years; women 55 years) European Guideline *Diabetes is regarded as a coronary heart disease (CHD) risk equivalent. HDL cholesterol 6 /dl counts as a negative risk factor; its pres ence removes 1 risk factor from the total count. Distribution of Absolute Risk* of CHD Within 1 Years European Populations Men Women <1% 6% 82% 1-2% 38% 16% 2-% 15% 2% >% <1% % Absolute Risk + of >2% of CHD Within 1 Year s by Age and Sex European Populations Years Men Women 25-3 35-5-5 55-6 65-7 % 1% 11% 3% 68% % <1% <1% 3.5% 6.% * Framingham - Anderson function 25-7 2% 1.6% + Framingham - Anderson function 한국성인의총콜레스테롤분포 Points 1-Yr-Risk % 남자 여자 1 % 12 1 8 Men = 7.9% 6 Women=9.6% 2 <13 1-16- 18-2- 22-2- 26- /dl 자료 : 보건복지부. 1998 년국민건강영양조사자료
연령군별고지혈증유병률 중간요약 (1) 25 2 고위험군은주로 ( 남성 ) 고령자에게많이발견된다. 15 1 5 남자여자전체 우리나라에서도고지혈증은주로고령에서많이발견된다. 3-39 -9 5-59 6-69 7 이상 자료 : 보건복지부. 21 년국민건강영양조사자료 얼마나낮추어야하는가? : LDL-C Goal Very High Risk ; 7 1 /dl High Risk ; 1 /dl Intermediate Risk ; 13 /dl Distribution of LDL-C C Levels in Patients With 2 or More CHD Risk Factors 5 No. of US Adults 3 (millions) 2 1 Mean LDL-C: 139.5 /dl (3.6 mmol/l) <6-129 13-159 159 16-3 (1.6-3.3) (3.-.1).1) (.1-7.8) LDL-C Level, /dl (mmol/l) NHANES III phase II (1988-199) 199) data. Adapted from Jacobson TA et al. Arch Intern Med.. 2;16:1361-1369. 1369. 스타틴의용량조절 P S2 A2 R1 Mt.Goal Effect of Statin Therapy on LDL-C Levels: The Rule of 6-6% -6% -6% A1 S 1 2 8 THREE-STEP TITRATION LDL - 3 % LDL - 5 % 1 2 3 5 6 % Reduction in LDL Cholesterol
25 스타틴의고용량에서의주의점 Myopathy 의발생이높은집단을이해! 고령 ( 주로 8 세이상 ) 몸집이작은사람 당뇨성신증등다기관의질병 약물병용 알코올의존경향 새로운 LDL 강하방법 ; Ezetimibe THREE-STEP TITRATION Statin 1 2 Statin 1 ONE-STEP COADMINISTRATION 1 2 3 5 6 % Reduction in LDL-C 8 + Ezetimibe 1 용량에따른 LDL 강하효과 Dose () of agent % Reduction Rosuva Atorva Simva / EZ Simva Lova / Prava TC LDL-C 5 1 2 22 27 1 2 27 3 1 2 8 32 1 2 1 / 1 8 37 8 8 2 55 Rule of 5s & 7s Roberts WC. Am J Cardiol. 1997;8:16-17. Stein E et al. J Cardiovasc Pharmacol Therapeut. 1997;2:7-16.
Localization of IV-Dosed 125 I-Gluc-Ezetimibe (SCH 6129) in Normal Rats 중간요약 (2) % IV dose 6 5 3 2 1.3 /kg, 3-hr post-dosing, n=/group EZ 는장에서의콜레스테롤흡수를선택적으로저해한다. EZ 는주로장관에만분포하기때문에, 기타조직에미치는효과가거의없다. S. Int. Rinse S. Int. Wall L. Int. Rinse L. Int. Wall Stomach Liver Pancreas Tissue Adrenal Kidney Lung Heart Spleen Teste Serum Relationship Between Dose of Ezetimibe and % Change in Plasma LDL-C EZ + Study: Efficacy on LDL-C From Baseline to Endpoint Mean (±S.E.M.) Percent Change in LDL-C 5% % -5% -1% -15% -2% Results from three Phase II Clinical Therapy Trials Placebo Ezetimibe 5 1 2 Daily Dose of Ezetimibe () Mean % Change -1-2 -3 - -5-6 EZ 1 + Simva 1 1 2 8-27* -36* -38* -6-5 * p<.1 combination therapy versus statin alone Davidson M et al. ACC 22: Abstract. Median % Change EZ + Statin Studies: Efficacy on TG Pooled Results -1-2 -3 - Lovastatin -12-25 * -2-29 * Pravastatin -21* Atorvastatin -33 * * p<.1 combination therapy versus statin alone Davidson M et al. ACC 22: Abstract. Ballantyne C et al. ACC 22: Abstract. Melani L et al. WCC 22: Abstract. Lipka L et al. WCC 22: Abstract. -1 Statins only + EZ 1 /d -2 Mean % Change Ezetrol + Statin Studies: Efficacy on HDL-C Pooled Results 1 8 6 2 Lovastatin 9* 9** 7 7 * p<.1 combination therapy versus statin alone ** p=.3 combination therapy versus statin alone Statins only + EZ 1 /d Pravastatin 8 Atorvastatin 7* Davidson M et al. ACC 22: Abstract. Ballantyne C et al. ACC 22: Abstract. Melani L et al. WCC 22: Abstract. Lipka L et al. WCC 22: Abstract.
25 Pooled Safety of Ezetimibe (EZ) Results from three Phase III Pooled Monotherapy Trials Ezetimibe in KOREANS No. of Patients (%) Placebo Ezetimibe ( n=31 ) ( n=1288 ) Adverse events 285 (66) 82 (62) Gastrointestinal 93 (22) 23 (18) DC 2 AE 11 (2.6) 51 () Liver function tests ( 3 x ULN) ALT 2 (<1) 7 (<1) AST 3 (<1) 6 (<1) GGT 1 (2) 2 (2) Total bilirubin ALP Creatine kinase (CK) elevations 5-1 x ULN 8 (<1) 1 x ULN 1 (<1) 3 (<1) Wk - 8 12 1 Placebo run-in & diet Eze1 + Simva1 (n = 55 pts) Simva1 (n = 55 pts) Ezetimibe in KOREANS ; good effects! Figure 2. Plot of LS Mean Percent Change from Baseline in LDL-C over Time: Modified Intention-to-Treat Approach Percent Change from Baseline i LDL-C -2 - -6 Week Baseline Week Week 8 Week 12 중간요약 (3) Ezetimibe 와 statin 의병용으로콜레스테롤의흡수와생합성을저해시킬수있다. Ezetimibe 의추가투여로 LDL 수치를추가로 2% 감소시킬수있다. Ezetimibe 와 statin 의병용으로부작용의증가를경험하지않고도 LDL 의목표치에도달할수있다 (8% 이상 ) Ezetimibe + Strategies for LDL reduction in elderly people Final Summary Dose titration according to the target goal ; 3 % or less = lower dose, or less potent statins ; 3 % or more = higher dose, or potent statins / low dose statin + Ezetimbe ; 5 % or more = tolerble dose of statin + Ezetimibe Many elderly people are under high risk. Ezetimibe-Boned Medication ; Evidence-Based Medicine for safe LDL reduction