血压和胆固醇降低在无心血管疾病的人。
Blood-Pressure and Cholesterol Lowering in Persons without Cardiovascular Disease.
机构信息
From the Population Health Research Institute, Hamilton Health Sciences (S.Y., E.L., J.B., R.M., J.P., H.J.), Department of Medicine (S.Y., E.L., R.M.), School of Rehabilitation Science (J.B.), Department of Clinical Epidemiology and Biostatistics (J.P.), McMaster University, Hamilton, ON, Li Ka Shing Knowledge Institute and Keenan Research Centre for Biomedical Science, St. Michael's Hospital, University of Toronto, Toronto (L.A.L.), and Institut Universitaire de Cardiologie et Pneumologie de Québec, Université Laval, Quebec, QC (G.D.) - all in Canada; St. John's Research Institute (P.P., D.X.), and St. John's Medical College (D.X.), Bangalore, India; Fundacion Oftalmológica de Santander and Instituto Masira, Medical School, Universidad de Santander, Bucaramanga (P.L.-J.), and Universidad del Norte, Barranquilla (J.L.A.) - both in Colombia; Fu Wai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (J.Z., L.L.); Dante Pazzanese Institute of Cardiology (A.A.) and HCor-Heart Hospital (L.S.P.), Sao Paulo; Institute of Cardiology, Kiev, Ukraine (A.P.); Hungarian Institute of Cardiology, Semmelweis University, Budapest, Hungary (M.K., K. Keltai); Hatter Institute for Cardiovascular Research in Africa, Department of Medicine, University of Cape Town, Soweto Cardiovascular Research Group, Cape Town, South Africa (K.S.); Institute of Clinical Cardiology in the Russian Cardiology Research Complex, Moscow (I.C.); the Department of Cardiology, Academic Medical Center, Amsterdam (R.J.G.P.); the Department of Medical Sciences, Cardiology, Clinical Research Center, Uppsala University, Uppsala, Sweden (C.H.); Universiti Teknologi Majlis Amansh Rakyat, Selayang, and University College Sedaya International University, Kuala Lumpur (K.Y.) - both in Malaysia; Lady Davis Carmel Medical Center, Ruth and Bruce Rappaport School of Medicine, Technion-Israel Institute of Technology, Haifa, Israel (B.S.L.); University Hospital Motol, Prague, Czech Repu
出版信息
N Engl J Med. 2016 May 26;374(21):2032-43. doi: 10.1056/NEJMoa1600177. Epub 2016 Apr 2.
BACKGROUND
Elevated blood pressure and elevated low-density lipoprotein (LDL) cholesterol increase the risk of cardiovascular disease. Lowering both should reduce the risk of cardiovascular events substantially.
METHODS
In a trial with 2-by-2 factorial design, we randomly assigned 12,705 participants at intermediate risk who did not have cardiovascular disease to rosuvastatin (10 mg per day) or placebo and to candesartan (16 mg per day) plus hydrochlorothiazide (12.5 mg per day) or placebo. In the analyses reported here, we compared the 3180 participants assigned to combined therapy (with rosuvastatin and the two antihypertensive agents) with the 3168 participants assigned to dual 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 heart failure, cardiac arrest, or revascularization. The median follow-up was 5.6 years.
RESULTS
The decrease in the LDL cholesterol level was 33.7 mg per deciliter (0.87 mmol per liter) greater in the combined-therapy group than in the dual-placebo group, and the decrease in systolic blood pressure was 6.2 mm Hg greater with combined therapy than with dual placebo. The first coprimary outcome occurred in 113 participants (3.6%) in the combined-therapy group and in 157 (5.0%) in the dual-placebo group (hazard ratio, 0.71; 95% confidence interval [CI], 0.56 to 0.90; P=0.005). The second coprimary outcome occurred in 136 participants (4.3%) and 187 participants (5.9%), respectively (hazard ratio, 0.72; 95% CI, 0.57 to 0.89; P=0.003). Muscle weakness and dizziness were more common in the combined-therapy group than in the dual-placebo group, but the overall rate of discontinuation of the trial regimen was similar in the two groups.
CONCLUSIONS
The combination of rosuvastatin (10 mg per day), candesartan (16 mg per day), and hydrochlorothiazide (12.5 mg per day) was associated with a significantly lower rate of cardiovascular events than dual placebo among persons at intermediate risk who did not have cardiovascular disease. (Funded by the Canadian Institutes of Health Research and AstraZeneca; ClinicalTrials.gov number, NCT00468923.).
背景
高血压和低密度脂蛋白（LDL）胆固醇升高会增加心血管疾病的风险。降低这两者都应该大大降低心血管事件的风险。
方法
在一项 2×2 析因设计的试验中，我们随机分配了 12705 名处于中间风险且没有心血管疾病的参与者，分别服用每天 10 毫克的瑞舒伐他汀或安慰剂，以及每天 16 毫克的坎地沙坦和每天 12.5 毫克的氢氯噻嗪或安慰剂。在报告的分析中，我们比较了分配给联合治疗组（瑞舒伐他汀和两种降压药物）的 3180 名参与者和分配给双重安慰剂组的 3168 名参与者。第一个主要复合终点是心血管原因死亡、非致死性心肌梗死或非致死性中风的复合终点，第二个主要复合终点另外包括心力衰竭、心脏骤停或血运重建。中位随访时间为 5.6 年。
结果
联合治疗组 LDL 胆固醇水平下降 33.7 毫克/分升（0.87 毫摩尔/升），比双重安慰剂组多，联合治疗组收缩压下降 6.2 毫米汞柱，比双重安慰剂组多。联合治疗组有 113 名（3.6%）参与者发生主要复合终点事件，双重安慰剂组有 157 名（5.0%）参与者发生主要复合终点事件（风险比，0.71；95%置信区间[CI]，0.56 至 0.90；P=0.005）。第二个主要复合终点分别在 136 名（4.3%）和 187 名（5.9%）参与者中发生（风险比，0.72；95%CI，0.57 至 0.89；P=0.003）。联合治疗组比双重安慰剂组更常见肌肉无力和头晕，但两组试验方案的总体停药率相似。
结论
在没有心血管疾病的中间风险人群中，与双重安慰剂相比，每天 10 毫克的瑞舒伐他汀、每天 16 毫克的坎地沙坦和每天 12.5 毫克的氢氯噻嗪联合使用的心血管事件发生率显著降低。（由加拿大卫生研究院和阿斯利康资助；ClinicalTrials.gov 编号，NCT00468923）。
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