From the Population Health Research Institute, Hamilton Health Sciences (S.Y., J.B., R.M., J.P., H.J., P.G., E.L.), Departments of Medicine (S.Y., R.M., E.L.) and Clinical Epidemiology and Biostatistics (J.P.), and School of Rehabilitation Science (J.B.), McMaster University, Hamilton, ON, Institut Universitaire de Cardiologie et Pneumologie de Québec, Université Laval, Quebec, QC (G.D.), and Li Ka Shing Knowledge Institute and Keenan Research Centre for Biomedical Science, St. Michael's Hospital, University of Toronto, Toronto (L.A.L.) - all in Canada; Fu Wai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (J.Z., L.L.); St. John's Medical College (D.X.) and St. John's Research Institute (D.X., P.P.), Bangalore, India; Fundacion Oftalmológica de Santander and Instituto Masira, Medical School, Universidad de Santander, Bucaramanga (P.L.-J.), and University of Quindio, Armenia (G.S.-V.) - both in Colombia; College of Medicine, University of the Philippines, Manila (A.D.); Dante Pazzanese Institute of Cardiology (A.A.) and HCor-Heart Hospital (L.S.P.), São Paulo; Institute of Cardiology, Kiev, Ukraine (A.P.); Hungarian Institute of Cardiology, Semmelweis University, Budapest (K. Keltai, M.K.); Hatter Institute for Cardiovascular Research in Africa, Department of Medicine, University of Cape Town, Soweto Cardiovascular Research Group, Cape Town, South Africa (K.S.); Department of Cardiology, Academic Medical Center, Amsterdam (R.J.G.P); Department of Medical Sciences, Cardiology, Clinical Research Center, Uppsala University, Uppsala, Sweden (C.H.); Institute of Clinical Cardiology in the Russian Cardiology Research Complex, Moscow (I.C.); Universiti Teknologi Majlis Amansh Rakyat, Selayang, and University College Sedaya International University, Kuala Lumpur - both in Malaysia (K.Y.); Lady Davis Carmel Medical Center, Ruth and Bruce Rappaport School of Medicine, Technion-Israel Institute of Technology, Haifa (B.S.L.); Universi
N Engl J Med. 2016 May 26;374(21):2021-31. doi: 10.1056/NEJMoa1600176. Epub 2016 Apr 2.
Previous trials have shown that the use of statins to lower cholesterol reduces the risk of cardiovascular events among persons without cardiovascular disease. Those trials have involved persons with elevated lipid levels or inflammatory markers and involved mainly white persons. It is unclear whether the benefits of statins can be extended to an intermediate-risk, ethnically diverse population without cardiovascular disease.
In one comparison from a 2-by-2 factorial trial, we randomly assigned 12,705 participants in 21 countries who did not have cardiovascular disease and were at intermediate risk to receive rosuvastatin at a dose of 10 mg per day or placebo. The first coprimary outcome was the composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke, and the second coprimary outcome additionally included revascularization, heart failure, and resuscitated cardiac arrest. The median follow-up was 5.6 years.
The overall mean low-density lipoprotein cholesterol level was 26.5% lower in the rosuvastatin group than in the placebo group. The first coprimary outcome occurred in 235 participants (3.7%) in the rosuvastatin group and in 304 participants (4.8%) in the placebo group (hazard ratio, 0.76; 95% confidence interval [CI], 0.64 to 0.91; P=0.002). The results for the second coprimary outcome were consistent with the results for the first (occurring in 277 participants [4.4%] in the rosuvastatin group and in 363 participants [5.7%] in the placebo group; hazard ratio, 0.75; 95% CI, 0.64 to 0.88; P<0.001). The results were also consistent in subgroups defined according to cardiovascular risk at baseline, lipid level, C-reactive protein level, blood pressure, and race or ethnic group. In the rosuvastatin group, there was no excess of diabetes or cancers, but there was an excess of cataract surgery (in 3.8% of the participants, vs. 3.1% in the placebo group; P=0.02) and muscle symptoms (in 5.8% of the participants, vs. 4.7% in the placebo group; P=0.005).
Treatment with rosuvastatin at a dose of 10 mg per day resulted in a significantly lower risk of cardiovascular events than placebo in an intermediate-risk, ethnically diverse population without cardiovascular disease. (Funded by the Canadian Institutes of Health Research and AstraZeneca; HOPE-3 ClinicalTrials.gov number, NCT00468923.).
先前的试验表明，使用他汀类药物降低胆固醇可以降低无心血管疾病人群发生心血管事件的风险。这些试验涉及血脂水平或炎症标志物升高的人群，主要是白人。他汀类药物的益处是否可以扩展到无心血管疾病的中等风险、种族多样化的人群中尚不清楚。
在一项来自 2×2 析因试验的比较中，我们在 21 个国家中随机分配了 12705 名无心血管疾病且处于中等风险的参与者，他们每天接受 10 毫克的瑞舒伐他汀或安慰剂治疗。主要复合终点为心血管原因导致的死亡、非致死性心肌梗死或非致死性卒中，次要复合终点另外包括血运重建、心力衰竭和复苏性心脏骤停。中位随访时间为 5.6 年。
瑞舒伐他汀组的平均低密度脂蛋白胆固醇水平比安慰剂组低 26.5%。瑞舒伐他汀组有 235 名（3.7%）参与者发生主要复合终点事件，安慰剂组有 304 名（4.8%）参与者发生主要复合终点事件（风险比，0.76；95%置信区间[CI]，0.64 至 0.91；P=0.002）。次要复合终点的结果与主要复合终点的结果一致（瑞舒伐他汀组有 277 名[4.4%]参与者发生次要复合终点事件，安慰剂组有 363 名[5.7%]参与者发生次要复合终点事件；风险比，0.75；95%CI，0.64 至 0.88；P<0.001）。根据基线心血管风险、血脂水平、C 反应蛋白水平、血压和种族或族裔群体进行亚组分析，结果也一致。在瑞舒伐他汀组，没有糖尿病或癌症的发生率增加，但白内障手术（瑞舒伐他汀组为 3.8%，安慰剂组为 3.1%；P=0.02）和肌肉症状（瑞舒伐他汀组为 5.8%，安慰剂组为 4.7%；P=0.005）的发生率增加。
在无心血管疾病的中等风险、种族多样化的人群中，每天服用 10 毫克瑞舒伐他汀治疗可显著降低心血管事件的风险，优于安慰剂。（由加拿大卫生研究院和阿斯利康资助；HOPE-3 ClinicalTrials.gov 编号，NCT00468923）。
