The effects of lowering LDL cholesterol with statin therapy in people at low risk of vascular disease: meta-analysis of individual data from 27 randomised trials.
The effects of lowering LDL cholesterol with statin therapy in people at low risk of vascular disease: meta-analysis of individual data from 27 randomised trials.
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DOI：
10.1016/s0140-6736(12)60367-5
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发表时间：
2012-08-11
期刊：
影响因子：
168.9
通讯作者：
Ford, I.
中科院分区：
文献类型：
--
作者：
Mihaylova, B.;Emberson, J.;Blackwell, L.;Keech, A.;Simes, J.;Barnes, E. H.;Voysey, M.;Gray, A.;Collins, R.;Baigent, C.;de Lemos, J.;Braunwald, E.;Blazing, M.;Murphy, S.;Downs, J. R.;Gotto, A.;Clearfield, M.;Holdaas, H.;Gordon, D.;Davis, B.;Koren, M.;Dahlof, B.;Poulter, N.;Sever, P.;Knopp, R. H.;Fellstrom, B.;Holdaas, H.;Jardine, A.;Schmieder, R.;Zannad, F.;Goldbourt, U.;Kaplinsky, E.;Colhoun, H. M.;Betteridge, D. J.;Durrington, P. N.;Hitman, G. A.;Fuller, J.;Neil, A.;Wanner, C.;Krane, V.;Sacks, F.;Moye, L.;Pfeffer, M.;Hawkins, C. M.;Braunwald, E.;Kjekshus, J.;Wedel, H.;Wikstrand, J.;Barter, P.;Keech, A.;Tavazzi, L.;Maggioni, A.;Marchioli, R.;Tognoni, G.;Franzosi, M. G.;Maggioni, A.;Bloomfield, H.;Robins, S.;Collins, R.;Armitage, J.;Keech, A.;Parish, S.;Peto, R.;Sleight, P.;Pedersen, T. R.;Ridker, P. M.;Holman, R.;Meade, T.;Simes, J.;Keech, A.;MacMahon, S.;Marschner, I.;Tonkin, A.;Shaw, J.;Serruys, P. W.;Nakamura, H.;Knatterud, G.;Furberg, C.;Byington, R.;Macfarlane, P.;Cobbe, S.;Ford, I.;Murphy, M.;Blauw, G. J.;Packard, C.;Shepherd, J.;Kjekshus, J.;Pedersen, T.;Wilhelmsen, L.;Braunwald, E.;Cannon, C.;Murphy, S.;Collins, R.;Armitage, J.;Bowman, L.;Parish, S.;Peto, R.;Sleight, P.;Baigent, C.;Landray, M.;Collins, R.;La Rosa, J.;Rossouw, J.;Probstfield, J.;Shepherd, J.;Cobbe, S.;Macfarlane, P.;Ford, I.
他汀类药物降低低密度脂蛋白胆固醇和预防血管事件，但其在低风险血管事件人群中的净效应仍不确定。这项荟萃分析包括来自22项他汀类药物与对照组试验的个体受试者数据（n=134 537;平均LDL胆固醇差异1.08 mmol/L;中位随访时间4.8年）和5项更多与更少他汀类药物的试验（n=39 612;差异0.51 mmol/L; 5.1年）。 主要血管事件是主要冠状动脉事件（即非致命性心肌梗死或冠状动脉死亡）、中风或冠状动脉血运重建。将受试者分为5类基线5年主要血管事件风险控制治疗（无他汀类药物或低强度他汀类药物）（<5%，≥5%至<10%，≥10%至<20%，≥20%至<30%，≥30%）;在每种情况下，估计每1.0 mmol/L LDL胆固醇降低的率比（RR）。使用他汀类药物降低LDL胆固醇可降低主要血管事件的风险（RR 0.79，95%CI 0.77 - 0.81，每降低1.0 mmol/L），在很大程度上与年龄、性别、基线LDL胆固醇或既往血管疾病以及血管和全因死亡率无关。在两个最低风险类别中，主要血管事件的比例降低至少与高风险类别一样大（从最低风险到最高风险每降低1·0 mmol/L的RR：0.62 [99%CI 0.47 - 0.81]、0.69 [99%CI 0.60 - 0.79]、0.79 [99%CI 0.74 - 0.85]、0.81 [99%CI 0.77 - 0.86]和0.79 [99%CI 0.74 - 0.84];趋势p=0·04），反映了这两种最低风险类别的主要冠状动脉事件显著降低（RR 0.57，99%CI 0.36 - 0.89，p= 0.0012和0.61，99%CI 0.50 - 0.74，p<0.0001）和冠状动脉血运重建（RR 0.52，99%CI 0.35 - 0.75和0.63，99%CI 0.51 - 0.79;均p<0.0001）。对于卒中，5年主要血管事件风险低于10%的受试者的风险降低（每降低1.0 mmol/L LDL胆固醇的RR为0.76，99% CI为0.61 - 0.95，p= 0.0012）也与高风险类别相似（趋势p= 0.3）。在无血管疾病史的受试者中，他汀类药物降低了血管性（每降低1.0 mmol/L LDL胆固醇的RR为0.85，95% CI为0.77 - 0.95）和全因死亡率（RR为0.91，95% CI为0.85 - 0.97）的风险，且降低比例与基线风险相似。没有证据表明他汀类药物降低LDL胆固醇会增加癌症发病率（RR/LDL胆固醇降低1.00，95% CI 0.96 - 1.04）、癌症死亡率（RR 0.99，95% CI 0.93 - 1.06）或其他非血管性死亡率。在5年主要血管事件风险低于10%的个体中，LDL胆固醇每降低1 mmol/L，5年内主要血管事件的绝对减少约为11/1000。这种益处大大超过了他汀类药物治疗的任何已知危害。根据目前的指南，这些个体通常不被认为适合降LDL他汀类药物治疗。因此，本报告建议，这些准则可能需要重新审议。英国心脏基金会英国医学研究理事会;英国癌症研究所;欧洲共同体生物医学方案;澳大利亚国家卫生和医学研究理事会;澳大利亚国家心脏基金会。
Statins reduce LDL cholesterol and prevent vascular events, but their net effects in people at low risk of vascular events remain uncertain. This meta-analysis included individual participant data from 22 trials of statin versus control (n=134 537; mean LDL cholesterol difference 1·08 mmol/L; median follow-up 4·8 years) and five trials of more versus less statin (n=39 612; difference 0·51 mmol/L; 5·1 years). Major vascular events were major coronary events (ie, non-fatal myocardial infarction or coronary death), strokes, or coronary revascularisations. Participants were separated into five categories of baseline 5-year major vascular event risk on control therapy (no statin or low-intensity statin) (<5%, ≥5% to <10%, ≥10% to <20%, ≥20% to <30%, ≥30%); in each, the rate ratio (RR) per 1·0 mmol/L LDL cholesterol reduction was estimated. Reduction of LDL cholesterol with a statin reduced the risk of major vascular events (RR 0·79, 95% CI 0·77–0·81, per 1·0 mmol/L reduction), largely irrespective of age, sex, baseline LDL cholesterol or previous vascular disease, and of vascular and all-cause mortality. The proportional reduction in major vascular events was at least as big in the two lowest risk categories as in the higher risk categories (RR per 1·0 mmol/L reduction from lowest to highest risk: 0·62 [99% CI 0·47–0·81], 0·69 [99% CI 0·60–0·79], 0·79 [99% CI 0·74–0·85], 0·81 [99% CI 0·77–0·86], and 0·79 [99% CI 0·74–0·84]; trend p=0·04), which reflected significant reductions in these two lowest risk categories in major coronary events (RR 0·57, 99% CI 0·36–0·89, p=0·0012, and 0·61, 99% CI 0·50–0·74, p<0·0001) and in coronary revascularisations (RR 0·52, 99% CI 0·35–0·75, and 0·63, 99% CI 0·51–0·79; both p<0·0001). For stroke, the reduction in risk in participants with 5-year risk of major vascular events lower than 10% (RR per 1·0 mmol/L LDL cholesterol reduction 0·76, 99% CI 0·61–0·95, p=0·0012) was also similar to that seen in higher risk categories (trend p=0·3). In participants without a history of vascular disease, statins reduced the risks of vascular (RR per 1·0 mmol/L LDL cholesterol reduction 0·85, 95% CI 0·77–0·95) and all-cause mortality (RR 0·91, 95% CI 0·85–0·97), and the proportional reductions were similar by baseline risk. There was no evidence that reduction of LDL cholesterol with a statin increased cancer incidence (RR per 1·0 mmol/L LDL cholesterol reduction 1·00, 95% CI 0·96–1·04), cancer mortality (RR 0·99, 95% CI 0·93–1·06), or other non-vascular mortality. In individuals with 5-year risk of major vascular events lower than 10%, each 1 mmol/L reduction in LDL cholesterol produced an absolute reduction in major vascular events of about 11 per 1000 over 5 years. This benefit greatly exceeds any known hazards of statin therapy. Under present guidelines, such individuals would not typically be regarded as suitable for LDL-lowering statin therapy. The present report suggests, therefore, that these guidelines might need to be reconsidered. British Heart Foundation; UK Medical Research Council; Cancer Research UK; European Community Biomed Programme; Australian National Health and Medical Research Council; National Heart Foundation, Australia.