Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials.
Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials.
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DOI：
10.1016/s0140-6736(10)61350-5
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发表时间：
2010-11-13
期刊：
影响因子：
168.9
通讯作者：
Collins, R.
中科院分区：
文献类型：
--
作者：
Baigent, C.;Blackwell, L.;Emberson, J.;Holland, L. E.;Reith, C.;Bhala, N.;Peto, R.;Barnes, E. H.;Keech, A.;Simes, J.;Collins, R.
标准他汀类药物治疗方案降低LDL胆固醇可降低大范围个体发生闭塞性血管事件的风险。我们的目的是评估他汀类药物治疗强化降低LDL胆固醇的安全性和有效性。我们对来自随机试验的个体受试者数据进行了荟萃分析，这些随机试验涉及至少1000名受试者，治疗持续时间至少为2年，治疗持续时间为更多与更少的强化他汀类药物方案（5项试验; 39612人;中位随访时间为5.1年）和他汀类药物与对照组（21项试验; 129526人;中位随访时间为4.8年）。 对于每种类型的试验，我们不仅计算了平均风险降低，而且还计算了随机化后1年时LDL胆固醇每降低1·0 mmol/L的平均风险降低。在更多与更少强化他汀类药物治疗的试验中，1年时LDL胆固醇进一步降低的加权平均值为0.51 mmol/L。与强度较低的方案相比，强度更高的方案产生了非常显著的15%，（95% CI 11-18; p<0.0001）进一步减少主要血管事件，包括冠心病死亡或非致死性心肌梗死分别显著减少13%（95% CI 7-19; p<0.0001），冠状动脉血运重建术为19%（95% CI 15-24; p<0.0001），缺血性卒中为16%（95% CI 5-26; p= 0.005）。LDL胆固醇每降低1.0 mmol/L，风险进一步降低与他汀类药物与对照试验中的比例降低相似。当两种类型的试验结合起来时，在所有类型的研究患者中，包括低强度或对照方案中LDL胆固醇低于2 mmol/L的患者，LDL胆固醇每降低1. 0 mmol/L，主要血管事件的减少比例相似（率比[RR] 0. 78，95% CI 0. 76-0. 80; p<0. 0001）。在所有26项试验中，LDL每降低1·0 mmol/L，全因死亡率降低10（RR 0.90，95% CI 0.87 - 0.93; p<0.0001），主要反映了冠心病死亡率的显著降低（RR 0.80，99% CI 0.74 - 0.87; p<0.0001）和其他心脏原因（RR 0.89，99%CI 0.81 - 0.98; p= 0.002），对卒中死亡无显著影响（RR 0·96，95% CI 0·84-1·09; p=0·5）或其他血管原因（RR 0·98，99% CI 0·81-1·18; p=0·8）。即使在低LDL胆固醇浓度下，也未观察到对癌症或其他非血管原因导致的死亡（RR 0.97，95% CI 0.92 - 1.03; p= 0.3）或癌症发病率（RR 1.00，95% CI 0.96 - 1.04; p= 0.9）的显著影响。进一步降低LDL胆固醇可安全地进一步降低心脏病发作、血运重建和缺血性卒中的发生率，每降低1.0 mmol/L，这些主要血管事件的年发生率降低1/5以上。在研究的胆固醇范围内没有任何阈值的证据，表明LDL胆固醇降低2-3 mmol/L将使风险降低约40- 50%。英国医学研究理事会、英国心脏基金会、欧洲共同体生物医学计划、澳大利亚国家健康和医学研究理事会和国家心脏基金会。
Lowering of LDL cholesterol with standard statin regimens reduces the risk of occlusive vascular events in a wide range of individuals. We aimed to assess the safety and efficacy of more intensive lowering of LDL cholesterol with statin therapy. We undertook meta-analyses of individual participant data from randomised trials involving at least 1000 participants and at least 2 years' treatment duration of more versus less intensive statin regimens (five trials; 39 612 individuals; median follow-up 5·1 years) and of statin versus control (21 trials; 129 526 individuals; median follow-up 4·8 years). For each type of trial, we calculated not only the average risk reduction, but also the average risk reduction per 1·0 mmol/L LDL cholesterol reduction at 1 year after randomisation. In the trials of more versus less intensive statin therapy, the weighted mean further reduction in LDL cholesterol at 1 year was 0·51 mmol/L. Compared with less intensive regimens, more intensive regimens produced a highly significant 15% (95% CI 11–18; p<0·0001) further reduction in major vascular events, consisting of separately significant reductions in coronary death or non-fatal myocardial infarction of 13% (95% CI 7–19; p<0·0001), in coronary revascularisation of 19% (95% CI 15–24; p<0·0001), and in ischaemic stroke of 16% (95% CI 5–26; p=0·005). Per 1·0 mmol/L reduction in LDL cholesterol, these further reductions in risk were similar to the proportional reductions in the trials of statin versus control. When both types of trial were combined, similar proportional reductions in major vascular events per 1·0 mmol/L LDL cholesterol reduction were found in all types of patient studied (rate ratio [RR] 0·78, 95% CI 0·76–0·80; p<0·0001), including those with LDL cholesterol lower than 2 mmol/L on the less intensive or control regimen. Across all 26 trials, all-cause mortality was reduced by 10% per 1·0 mmol/L LDL reduction (RR 0·90, 95% CI 0·87–0·93; p<0·0001), largely reflecting significant reductions in deaths due to coronary heart disease (RR 0·80, 99% CI 0·74–0·87; p<0·0001) and other cardiac causes (RR 0·89, 99% CI 0·81–0·98; p=0·002), with no significant effect on deaths due to stroke (RR 0·96, 95% CI 0·84–1·09; p=0·5) or other vascular causes (RR 0·98, 99% CI 0·81–1·18; p=0·8). No significant effects were observed on deaths due to cancer or other non-vascular causes (RR 0·97, 95% CI 0·92–1·03; p=0·3) or on cancer incidence (RR 1·00, 95% CI 0·96–1·04; p=0·9), even at low LDL cholesterol concentrations. Further reductions in LDL cholesterol safely produce definite further reductions in the incidence of heart attack, of revascularisation, and of ischaemic stroke, with each 1·0 mmol/L reduction reducing the annual rate of these major vascular events by just over a fifth. There was no evidence of any threshold within the cholesterol range studied, suggesting that reduction of LDL cholesterol by 2–3 mmol/L would reduce risk by about 40–50%. UK Medical Research Council, British Heart Foundation, European Community Biomed Programme, Australian National Health and Medical Research Council, and National Heart Foundation.