MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20536 high-risk individuals: a randomised placebo-controlled trial
MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20536 high-risk individuals: a randomised placebo-controlled trial
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DOI：
10.1016/s0140-6736(02)09327-3
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发表时间：
2002-07-06
期刊：
影响因子：
168.9
通讯作者：
Peto, R
中科院分区：
文献类型：
--
作者：
Collins, R;Armitage, J;Peto, R
背景在西方人群中，低密度脂蛋白胆固醇的范围通常在整个范围内，较低的血液浓度与较低的心血管疾病风险相关。因此，在这些人群中，降低LDL胆固醇可能会减少血管疾病的发生，这在很大程度上与初始胆固醇浓度无关。年龄在40-80岁之间的冠心病、其他动脉闭塞性疾病或糖尿病患者被随机分配接受辛伐他汀40 mg/d（平均依从性：85%）或匹配安慰剂（平均非研究他汀类药物用途：17%）。分析的是首次发生的特定事件，并比较所有辛伐他汀分配与所有安慰剂分配的参与者。这些“意向性治疗“比较评估了约三分之二（85%-17%）在计划的5年治疗期间服用他汀类药物的效果，其产生的LDL胆固醇平均差异为1.0 mmol/L（约为每日实际使用40 mg辛伐他汀效果的三分之二）。主要结局为死亡率（用于总体分析）和致死性或非致死性血管事件（用于亚类分析），并对癌症和其他主要发病率进行辅助评估。（辛伐他汀组10269例中死亡1328例[12.9%]，安慰剂组10267例中死亡1507例[14.7%]; p=0.0003），因为冠状动脉死亡率按比例降低了18%（SE 5），（587例[5.7%] vs 707例[6.9%]; p=0.0005），其他血管性死亡略微显著减少（194 [1.9%] vs 230 [2.2%]; p=0.07），非血管性死亡无显著减少（547 [5.3%] vs 570 [5.6%]; p=0-4）。非致命性心肌梗死或冠状动脉死亡的首次事件发生率非常显着降低了约四分之一（898 [8.7%] vs 1212 [11.8%]; p
Background Throughout the usual LDL cholesterol range in Western populations, lower blood concentrations are associated with lower cardiovascular disease risk. In such populations, therefore, reducing LDL cholesterol may reduce the development of vascular disease, largely irrespective of initial cholesterol concentrations.Methods 20 536 UK adults (aged 40-80 years) with coronary disease, other occlusive arterial disease, or diabetes were randomly allocated to receive 40 mg simvastatin daily (average compliance: 85%) or matching placebo (average non-study statin use: 17%). Analyses are of the first occurrence of particular events, and compare all simvastatin-allocated versus all placebo-allocated participants. These "Intention-to-treat"comparisons assess the effects of about two-thirds (85% minus 17%) taking a statin during the scheduled 5-year treatment period, which yielded an average difference in LDL cholesterol of 1.0 mmol/L (about two-thirds of the effect of actual use of 40 mg simvastatin daily). Primary outcomes were mortality (for overall analyses) and fatal or non-fatal vascular events (for subcategory analyses), with subsidiary assessments of cancer and of other major morbidity.Findings All-cause mortality was significantly reduced (1328 [12.9%] deaths among 10 269 allocated simvastatin versus 1507 [14.7%] among 10 267 allocated placebo; p=0.0003), due to a highly significant 18% (SE 5) proportional reduction in the coronary death rate (587 [5.7%] vs 707 [6.9%]; p=0.0005), a marginally significant reduction in other vascular deaths (194 [1.9%] vs 230 [2.2%]; p=0.07), and a non-significant reduction in non-vascular deaths (547 [5.3%] vs 570 [5.6%]; p=0-4). There were highly significant reductions of about one-quarter in the first event rate for non-fatal myocardial infarction or coronary death (898 [8.7%] vs 1212 [11.8%]; p