Presentation Title R3 이지영 / 김 수 중교 수 님

Introduction Lowering LDL cholesterol levels with statins : Reduce the risk of cardiovascular disease Vascular disease, elevated lipid levels, elevated inflammatory markers, hypertension, or diabetes. Primary prevention of CVD among persons without cardiovascular disease, regardless of risk factors  Has not been established Previous trials: In North America or Europe, Involve mainly white persons HOPE(Heart Outcomes Prevention Evaluation)-3 trial 80% of the global burden of cardiovascular disease occurs in low- and middle-income countries Asian persons are thought to be higher risk for the side effects of statin Benefits of statins to an intermediate-risk, ethnically diverse population without cardiovascular disease Low-dose rosuvastatin -10mg qd (JUPITER: 20mg)

Methods Double-blind, randomized, placebo-controlled trial 228 centers in 21 countries 2-by-2 factorial design Persons who did not have cardiovascular disease & were at intermediate risk * Intermediate risk: Annual risk of major cardiovascular events- “~1%” Rosuvastatin 10 mg/day OR Placebo Candesartan 16 mg/day + Hydrochlorothiazide 12.5 mg/day OR Placebo Combination of intervention for prevention of cardiovascular Follow-up visits occurred at 6 weeks, 6 months and every 6 months Lipid levels were measured at baseline, 1 year, 3 years, and the end of trial From April November 2010

Methods First coprimary outcome Death from cardiovascular causes Nonfatal myocardial infarction Nonfatal stroke Second coprimary outcome additionally included Resuscitated cardiac arrest Heart failure Revascularization Secondary outcome additionally included Angina with evidence of ischemia

Results

Methods The median follow-up: 5.6 years

Methods

mg/dl (26.5%) 0.23g/L (22.0%) 0.19mg/L

Methods

Conclusions Elevated No significant difference between 2 groups *More participants in the rosuvastatin group underwent cataract surgery (241 [3.8%] vs. 194 [3.1%], P = 0.02)

Conclusions HOPE-3 evaluated cholesterol lowering with the use of a low dose of rosuvastatin in a diverse population of persons who did not have cardiovascular disease and who were at intermediate risk. There was a significant reduction in the risk of cardiovascular events with rosuvastatin.

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소위 LDL 가설 (LDL 이 atheroscloertic vascular dx 발절의 개연성 있는 요인 ) statin 과 상관없이 LDL 만 낮추면 되나 ? Statin 가설 : statin 이 LDL 을 낮춰줘서 좋은것뿐 아니라, statin 자체의 특수한 효과가 있다. LDL lowering effect + "pleiotropic effect" 추측 기전 : endhthelial dysfunction, NO 의 bioavailabiity 증가, antioxidant properties inflammation 억제 " pleiotropic effects" rosuvastatin 임상연구에서 LDL 낮추기 + high sensitivity CRP 낮추기 simvastatin 투여해서 심장병 재발 감소 4S 연구 심장병 없는, 콜레스테롤만 높은 백인남자 프라바스타틴 투여하면서 심장병 낮아짐. WOSCOPS 연구 심장병 없는, 당뇨환자에서 아토바스타틴 투여하면서 심장병 예방함. CARDS 연구 --> 다시 LDL 가설이 반박 IMPROVE-IT : 심바스타틴 40 단독 과 심바 + 에제티미브 ( 바이토린 ) LDL 70 유지 LDL 50 이하로 유지 심장병 더 많이 예방됨. : statin 말고 LDL 더 낮추는 다른 약제 추가해서 떨어트리니까, 심장병 적게 발생 PROVE-IT: 프라바스타틴 40( 효과는 25%-40% 으로 적음 ) 과 아토바스타틴 80( 효과좋음 ) 아토바주고 더 떨어지니까, 심장발생 감소. TNT : 아토바를 10 과 으로 많이 주고 많이 떨어지니까, 심장발생 감소. --> 다시 LDL 가설이 반박 IMPROVE-IT : 심바스타틴 40 단독 과 심바 + 에제티미브 ( 바이토린 ) LDL 70 유지 LDL 50 이하로 유지 심장병 더 많이 예방됨. : statin 말고 LDL 더 낮추는 다른 약제 추가해서 떨어트리니까, 심장병 적게 발생 "the lower, the better " LDL 계속 떨어뜨리면 좋나 ? 70mg/dl 밑으로 아예 낮추면 ?? -> 연구 계속 실패 중 HOPE-3 trial: 백인만 아니고 & risk 적은 환자들에서 statin 효과는 ?