Author:Downs JR， Clearfield M， Weis S， Whitney E， Shapiro DR， Beere PA， Langendorfer A， Stein EA， Kruyer W， Gotto AM Jr. Wilford Hall Medical Center， Lackland Air Force Base， San Antonio， Tex， USA.

CONTEXT: Although cholesterol-reducing treatment has been shown to reduce fatal and nonfatal coronary disease in patients with coronary heart disease (CHD)， it is unknown whether benefit from the reduction of low-density lipoprotein cholesterol (LDL-C) in patients without CHD extends to individuals with average serum cholesterol levels， women， and older persons. OBJECTIVE: To compare lovastatin with placebo for prevention of the first acute major coronary event in men and women without clinically evident atherosclerotic cardiovascular disease with average total cholesterol (TC) and LDL-C levels and below-average high-density lipoprotein cholesterol (HDL-C) levels. DESIGN: A randomized， double-blind， placebo-controlled trial. SETTING: Outpatient clinics in Texas.

PARTICIPANTS: A total of 5608 men and 997 women with average TC and LDL-C and below-average HDL-C (as characterized by lipid percentiles for an age- and sex-matched cohort without cardiovascular disease from the National Health and Nutrition Examination Survey [NHANES] III). Mean (SD) TC level was 5.71 (0.54) mmol/L (221 [21] mg/dL) (51 st percentile)， mean (SD) LDL-C level was 3.89 (0.43) mmol/L (150 [17] mg/dL) (60th percentile)， mean (SD) HDL-C level was 0.94 (0.14) mmol/L (36 [5] mg/dL) for men and 1.03 (0.14) mmol/L (40 [5] mg/dL) for women (25th and 16th percentiles， respectively)， and median (SD) triglyceride levels were 1.78 (0.86) mmol/L (158 [76] mg/dL) (63rd percentile). INTERVENTION: Lovastatin (20-40 mg daily) or placebo in addition to a low-saturated fat， low-cholesterol diet. MAIN OUTCOME MEASURES: First acute major coronary event defined as fatal or nonfatal myocardial infarction， unstable angina， or sudden cardiac death.

RESULTS: After an average follow-up of 5.2 years， lovastatin reduced the incidence of first acute major coronary events (1 83 vs 116 first events; relative risk [RR]， 0.63; 95% confidence interval [CI]， 0.50-0.79; P<.001)， myocardial infarction (95 vs 57 myocardial infarctions; RR， 0.60; 95% CI， 0.43-0.83; P=.002)， unstable angina (87 vs 60 first unstable angina events; RR， 0.68; 95% CI， 0.49-0.95; P=.02)， coronary revascularization procedures (157 vs 106 procedures; RR， 0.67; 95% CI， 0.52-0.85; P=.001)， coronary events (215 vs 163 coronary events; RR， 0.75; 95% CI， 0.61-0.92; P =.006)， and cardiovascular events (255 vs 194 cardiovascular events; RR， 0.75; 95% CI， 0.62-0.91; P = .003). Lovastatin (20-40 mg daily) reduced LDL-C by 25% to 2.96 mmol/L (115 mg/dL) and increased HDL-C by 6% to 1.02 mmol/L (39 mg/dL). There were no clinically relevant differences in safety parameters between treatment groups.

CONCLUSIONS: Lovastatin reduces the risk for the first acute major coronary event in men and women with average TC and LDL-C levels and below-average HDL-C levels. These findings support the inclusion of HDL-C in risk-factor assessment， confirm the benefit of LDL-C reduction to a target goal， and suggest the need for reassessment of the National Cholesterol Education Program guidelines regarding pharmacological intervention.

出处：JAMA. 1998 May 27;279(20):1615-22

[目的] 研究对于血浆胆固醇在合适水平或轻度升高的无冠心病者， 在饮食治疗的基础上加用洛伐他汀， 能否减少主要冠心病事件发生的危险性。

[对象] 5608名男性(年龄45～73岁)和997名女性(年龄55～73岁)， 血浆胆固醇4.7～6.8mmol/L(LDL-C3.4～4.9mmol/L)， TG＜4.5mmol/L。凡有心血管疾病史、肾病综合征、胰岛素依赖型或未控制的糖尿病、未控制的高血压者均予排除。
[治疗与随访] 随机安慰剂对照试验， 治疗组服用洛伐他汀20mg/d， 若LDL-C仍&gt;2.8mmol/L， 增加剂量至40mg/d。追踪观察平均5.2年。

[结果] 洛伐他汀治疗使LDL-C和TG分别降低25%和18%， 使HDL-C升高6%。洛伐他汀治疗使一级终点(心肌梗塞、不稳定型心绞痛和心脏猝死)相对危险性下降37%; 心肌梗塞的相对危险性下降40%; 不稳定型心绞痛的相对危险性下降32%; 使需接受冠脉再通术的相对危险性下降63%。治疗组与安慰组间总死亡率和肿瘤发生率无差别。因药物的不良反应而对导致停药者在治疗组为13.6%， 安慰剂组为13.8%。

[结论] 对于血浆LDL-C和TG水平正常或轻度升高且无冠心病者，洛伐他汀治疗5.2年可降低急性冠脉事件发生的危险性。