Background—Patients with primary elevations of LDL-C ≥190 mg/dL are at a higher risk of atherosclerotic cardiovascular disease as a result of long-term exposure to markedly elevated LDL-C levels. Therefore, initiation of statin therapy is recommended for these individuals. However, there is a lack of randomised trial evidence supporting these recommendations in primary prevention. In the present analysis we provide hitherto unpublished data on the cardiovascular effects of LDL-C lowering among a primary prevention population with LDL-C ≥190 mg/dL.Methods—We aimed to assess the benefits of LDL-C lowering on cardiovascular outcomes among individuals with primary elevations of LDL-C ≥190 mg/dL without pre-exiting vascular disease at baseline. We carried out post-hoc analyses from the West Of Scotland Coronary Prevention Study (WOSCOPS) randomised, placebo-controlled trial, and observational post-trial long-term follow-up, after excluding individuals with evidence of vascular disease at baseline. WOSCOPS enrolled 6595 men aged 45-64 years, who were randomised to pravastatin 40 mg/d or placebo. In the present analyses, 5529 participants without evidence of vascular disease were included, stratified by LDL-C levels into those with LDL-C <190 mg/dL (n=2969; mean LDL-C 178±6 mg/dL) and those with LDL-C ≥190 mg/dL (n=2560; mean LDL-C 206±12 mg/dL).The effect of pravastatin versus placebo on coronary heart disease (CHD) and major adverse cardiovascular events (MACE) were assessed over the 4.9-year randomised-controlled trial phase and on mortality outcomes over a total of 20-years of follow-up.Results—Among 5529 individuals without vascular disease, pravastatin reduced the risk of CHD by 27% (p=0.002) and MACE by 25% (p=0.004) consistently among those with and without LDL-C ≥190 mg/dL (p-interaction >0.9). Among individuals with LDL-C ≥190 mg/dL, pravastatin reduced the risk of CHD by 27% (p=0.033) and MACE by 25% (p=0.037) during the initial trial phase and the risk of CHD death, cardiovascular death and all-cause mortality by 28% (p=0.020), 25% (p=0.009) and 18% (p=0.004), respectively, over a total of 20-years of follow-up.Conclusions—The present analyses provide robust novel evidence for the short and long-term benefits of lowering LDL-C for the primary prevention of cardiovascular disease among individuals with primary elevations of LDL-C ≥190 mg/dL.

背景— LDL-C初次升高≥190mg / dL的患者由于长期暴露于明显升高的LDL-C水平而患上动脉粥样硬化性心血管疾病的风险较高。因此，建议这些人开始他汀类药物治疗。但是，缺乏在初级预防中支持这些建议的随机试验证据。在当前的分析中，我们提供了迄今为止尚未发表的有关LDL-C≥190mg / dL的一级预防人群中LDL-C降低对心血管的影响的数据。方法—我们旨在评估LDL-C降低对初次LDL-C≥190 mg / dL升高而在基线时未患有血管疾病的个体的心血管结局的益处。在排除基线有血管疾病证据的个体后，我们对苏格兰西部冠状动脉预防研究（WOSCOPS）进行了随机，安慰剂对照试验和观察性的试验后长期随访，进行了事后分析。WOSCOPS招募了6595名年龄在45-64岁之间的男性，他们随机分配给普伐他汀40 mg / d或安慰剂。在本次分析中，纳入了5529名无血管疾病证据的参与者，按LDL-C水平分为LDL-C <190 mg / dL（n = 2969；平均LDL-C 178±6 mg / dL）和那些。 LDL-C≥190mg / dL（n = 2560；平均LDL-C 206±12 mg / dL）。结果—在5529名无血管疾病的个体中，普伐他汀在LDL-C≥190 mg / dL和不存在LDL-C≥190mg / dL（p-互动> 0.9）。在LDL-C≥190 mg / dL的个体中，普伐他汀在初始试验阶段将CHD的风险降低了27％（p = 0.033），将MACE降低了25％（p = 0.037），并降低了CHD死亡，心血管死亡的风险。在长达20年的随访中，全因死亡率分别降低了28％（p = 0.020），25％（p = 0.009）和18％（p = 0.004）。结论—本研究为降低LDL-C初步升高对LDL-C≥190 mg / dL的个体的心血管疾病的近期和长期获益提供了有力的新证据。