Intensive lowering of LDL cholesterol with 80 mg versus 20 mg simvastatin daily in 12,064 survivors of myocardial infarction: a double-blind randomised trial.

Intensive lowering of LDL cholesterol with 80 mg versus 20 mg simvastatin daily in 12,064 survivors of myocardial infarction: a double-blind randomised trial.
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DOI:
10.1016/s0140-6736(10)60310-8
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发表时间:
2010-11-13
期刊:
影响因子:
168.9
通讯作者:
Walton, E.
Walton, E.
中科院分区:
医学1区
文献类型:
--
作者:
Armitage, Jane;Bowman, Louise;Wallendszus, Karl;Bulbulia, Richard;Rahimi, Kazem;Haynes, Richard;Parish, Sarah;Peto, Richard;Collins, Rory;Meade, T.;Sleight, P.;Collins, R.;Armitage, J.;Bowman, L.;Parish, S.;Peto, R.;Barton, J.;Bray, C.;Wincott, E.;Dayanandan, R.;Clarke, R.;Graham, I.;Simpson, D.;Warlow, C.;Wilken, D.;Tobert, J.;Mushner, T.;Doll, R.;Wilhelmsen, L.;Fox, K.;Hill, C.;Sandercock, P.;Webster, J.;Henderson, J.;Nixon, A.;Lackie, S.;Thompson, J.;Brown, M.;Blackwood, S.;Morgan, M.;Rhoden, W.;Saeed, B.;Houghton, M.;Nicholson, A.;Simpson, C.;Hoburn, B.;Cooper, I.;Gallivan, A.;Pickerell, E.;Hancock, J.;Watkinson, J.;Ryder, B.;Jones, S.;Burbridge, W.;Kitchen, M.;Leary, H. O.;Verow, C.;Meynell, L.;Rollinson, L.;Bain, S.;Jones, A.;Jewkes, C.;Russon, C.;Bateson, M.;Gill, P.;Nicol, J.;Bayly, G.;Stansbie, D.;Andrews, G.;Halestrap, M.;Meredith, J.;Best, R.;Appleyard, D.;Briggs, R.;Wareing, H.;Holmes, K.;Holt, J.;Kenyon, M.;White, C.;Khalifa, M.;Newton, D.;Wass, A.;Watkinson, R.;Creamer, J.;Anderson, S.;Bethell, A.;Butler, C.;Castro, K.;Washington, M.;Weston, M.;Cleaver, K.;Machin, J.;Wray, R.;Sinclair, J.;Van Aalst, A.;Been, M.;Mattu, R.;Bates, D.;Burke, A.;Gill, L.;Walton, E.;Cowley, M.;Robson, H.;Graham, A.;Rose, G.;Kerr, M.;Mallinson, J.;Peascod, B.;Donnelly, R.;Kalk, J.;Scott, A.;Gibson, T.;Hannah, J.;Henshaw, L.;Margetts, M.;Pearson, N.;Frost, S.;Murray, S.;Marshall, A.;Went, J.;Inman, A.;Simmonds, J.;Teasdale, A.;Kemp, T.;Roberts, G.;Kooner, J.;Cahill, S.;Lloyd, M.;Molloy, O.;Wigley, J.;Galvin, M.;Wilder, C.;Lindley, R.;Shaw, S.;Swainson, C.;Hillis, L.;Johnston, J.;Johnstone, A.;Miller, D.;Kennedy, M.;Mushahwar, S.;Savage, M.;Appleyard, D.;Ayer, G.;Schofield, J.;Greenhalgh, S.;Parks, J.;Speak, S.;Coulson, C.;Papouchado, M.;Carpenter, R.;Wisby, J.;Cobbe, S.;Campbell, C.;Hunter, J.;Young, H.;Gallacher, M.;Lindsay, D.;Halliday, A.;Godfrey, S.;Donahoo, L. O.;Chambers, J.;Wierzbicki, A.;Jones, A.;Parkin, D.;Nwafor, K.;Oldroyd, K.;Vallance, B.;Cunningham, N.;Moreland, G.;Oldroyd, C.;Young, H.;Crawford, M.;Hillson, R.;Knott, K.;Mahabir, N.;Crouch, A.;MacDonald, Y.;Bellamy, C.;Green, J.;Brown, L.;Heron, J.;Jones, N.;Roberts, M.;Hainsworth, D.;Williams, J.;Barnes, P.;Fitchet, A.;Longworth, C.;Davidson, J.;Irvine, N.;Oliver, R.;Pond, C.;Nuttall, M.;Mostyn, R. Lloyd;Brown, M.;Barrowcliffe, J.;Blackburn, S.;Furnell, W.;Webster, S.;Wheatley, L.;Hudson, I.;Pohl, J.;Nicholson, S.;Mallya, S.;Nash, M.;Spruce, J.;Bonner, A.;Leather, J.;Searle, A.;Davies, E.;Egdell, R.;Price, B.;Bennett, A. Taylor;Horton, S.;Cunnington, A.;Giles, P.;Sidaway, J.;Tomlinson, L.;Walton, E.;Hawkins, L.;Long, J.;Murphy, J.;Brennan, G.;Boon, M.;Cassidy, S.;Rodger, C.;Hunter, J.;McNeilly, A.;Moreland, G.;Radcliffe, A.;Farrer, M.;Bluett, J.;Cowell, L.;Farrell, A.;Gilroy, S.;Warren, S.;MacConnell, T.;Burtchaell, S.;Williams, L.;Rylance, P.;Hodgson, A.;Hill, K. Kertland;Robinson, L.;Smallwood, A.;Lomas, S.;Ball, J.;Benbow, S.;Hardy, K.;Gerrard, M.;Langley, C.;Beattie, M.;Fagan, C.;Green, B.;Pringle, T.;Hanna, H.;Mackintosh, A.;Watson, E.;Swan, J.;Appleyard, D.;McSorland, D.;Thompson, G.;Neill, C. O.;Curless, R.;Doig, C.;McKenna, P.;Martin, J.;Murdy, J.;Scott, A.;Martin, S.;Birkhead, J.;Donnell, J. O.;Fox, C.;Dixon, S.;Hassall, A.;Tanqueray, E.;Vass, D.;Cosford, I.;Elderkin, M.;McKenzie, P.;Gray, T.;Appleyard, D.;Holmshaw, N.;McKinnon, A.;Bennett, A. Taylor;Ali, I.;Stephens, N.;Banfield, A.;Chester, L.;Wiseman, J.;Harrisingh, N.;Patel, R.;Thaker, P.;Armitage, J.;Watkins, H.;Beebe, S.;Fitzgerald, J.;Godden, J.;Lawson, A.;Lochhead, H.;Taylor, A.;Turner, S.;Rowlands, D.;Cooper, A.;Graham, J.;Hennessy, S.;Rashid, T.;Smith, C.;Nyman, C.;Adams, J.;Hardwick, A.;Buck, P.;Pattinson, C.;Trigg, J.;McLeod, A.;Gardner, S.;Haimes, L.;Orr, S.;Johns, S.;Capps, N.;Cook, A.;Donaldson, D.;Keighley, C.;Stiles, C.;Asbridge, S.;Buller, N.;Townend, J.;Hooks, J.;Jewkes, C.;Jones, H.;Watson, R.;Salt, P.;Francis, M.;MacLeod, D.;Allcoat, P.;Stuart, R.;Reynolds, T.;Maiden, J.;Reynolds, J.;Murray, D.;MacFadyen, R.;Potts, L.;Smith, A.;King, L.;Muthusamy, R.;Jones, M.;Lawan, M.;Nixon, J.;Wasnidge, L.;Weston, C.;Hutchesson, A.;Evans, J.;Morris, K.;Oultram, M.;Armitage, M.;Skule, R.;Cope, C.;Page, M.;Fleming, S.;Andain, K.;Parrett, M.;Soper, R.;MacLeod, K.;Gordon, K.;Green, E.;Havill, S.;Stewart, V.;Allen, S.;Henson, S.;Rimmer, C.;Davies, J.;Javed, M.;Norris, A.;Williams, M.;Khan, S.;Dobie, G.;Fitton, J.;Gilbert, S.;Davenport, C.;Williamson, M.;Vincent, R.;Joyce, E.;Reckless, J.;Bishop, A.;Brice, L.;Carpenter, R.;Field, P.;Shute, C.;Pope, S.;Stacey, D.;Findlay, I.;Campbell, C.;Hunter, J.;Gallacher, M.;Labib, M.;Hodgson, A.;Sidaway, J.;Beddoe, L.;Reed, J.;Barron, J.;Odemuyiwa, O.;Bradford, B.;McDonnell, M.;West, L.;Beck, P.;Gilbey, S.;Clarkson, A.;Drury, K.;Hall, S.;Quartey, D.;Whittam, B.;Lund, D.;Stott, L.;Griffiths, H.;Appleyard, D.;Fitzgerald, J.;Kudarenko, A.;Watkins, J.;Golledge, S.;Pottle, J.;Little, S.;Paine, B.;Shears, C.;Baxter, M.;Wilkinson, P.;Chambers, R.;Hamper, C.;Hollister, E.;Ramsay, H.;Barber, J.;Hopkins, T.;Hughes, L.;Whittaker, J. Elson;Verow, C.;Burke, R. Lambley;Lloyd, C.;Dhawan, J.;John, J.;Bramley, D.;Catchpole, A.;Colecchia, A.;Gray, C.;LeQuelenec, M.;Remington, D.;Wiseman, J.;Gray, C.;Anderson, P.;Woolass, R.;Thomas, P.;Weston, C.;Guy, F.;Lynch, J.;Thomas, R.;Coates, S.;Gait, M.;Waller, D.;Elkins, K.;Franklin, M.;Moore, L.;Signy, M.;Chilton, R.;Joyce, E.;Wrapson, C.;Wiltshire, C.;Lewis, P.;Curtis, J.;Toole, J. O.;Scanlon, S.;Carey, C.;Dobson, L.;Gould, M.;Mansfield, H.;Ranson, G.;Rodaway, M.;Germon, J.;Cockcroft, J.;McDowell, I.;Field, R.;Whiting, J.;Dennison, C.;Roberts, D.;Cooper, M.;Davies, C.;Fitton, J.;Hutt, L.;Radford, L.;Ward, L.;Williamson, M.;McAlpine, H.;Dougall, H.;Robertson, L.;Scott, L.;Young, H.;Humphrey, P.;Saminaden, S.;Watling, D.;Davies, J.;Owen, L.;Clements, M.;Walker, E.;Atkins, E.;Lindley, R.;Shaw, T.;Swainson, C.;Webb, D.;MacCallum, H.;Markie, D.;Melville, V.;Adamson, L.;Johnston, A.;Polukord, E.;Rudden, M.;Hogan, J.;Lie, F.;Badger, V.;Duffy, S.;Mitchell, C.;MacQueen, E.;Baxter, R.;Campbell, S.;McDonald, L.;Wood, H.;Munro, A.;Pycock, C.;Cadwell, J.;Doughty, A.;Harvey, M.;Price, S.;Aldersley, M.;Lock, S.;Pendrey, P.;Barton, J.;Bray, C.;Dayanandan, R.;Wmcott, E.;Achiri, P.;Anderson, C.;Benham, J.;Bojowsky, H.;Boller, I.;Booker, V.;Brewer, A.;Brindley, G.;Cobb, L.;Collett, A.;Corbett, M.;Crowther, J.;Pour, S. Danesh;Edmunds, K.;Fortun, A.;Grimsey, T.;Harwood, C.;Hope, C.;Jones, R.;Jones, S.;Kidney, K.;King, M.;Knight, S.;Lang, H.;Madgwick, Z.;Marsden, C.;Matthews, C.;Matthewson, M.;Miller, J.;Moss, B.;Mostefai, Y.;Murphy, K.;Naughten, A.;Pickworth, S.;Radley, A.;Southren, S.;Sutherland, S.;Tong, R.;Turakani, M.;Umbrath, M.;Armitage, J.;Baigent, C.;Bowman, L.;Bulbulia, R.;Chen, Z.;Clarke, R.;Collins, R.;Dunachie, S.;Dasgupta, T.;Haynes, R.;Landray, M.;Mafham, M.;Majoni, W.;Murray, C.;Naessens, K.;Porter, T.;Rahimi, K.;Reith, C.;Clarke, M. Taylor;Turnbull, C.;Walter, K.;Harding, P.;Lay, M.;Wallendszus, K.;Berry, C.;Bettesworth, H.;Booth, J.;Bowes, M.;Bu, Y.;Charles, A.;Cody, A.;Cox, J.;Emberson, J.;Goodwin, N.;Hurt, C.;Link, E.;McCabe, P.;Munday, A.;Murawska, A.;Offer, A.;Palmer, A.;Parish, S.;Peto, R.;Prajapati, N.;Tochlin, S.;Young, A.;Young, A.;Clark, S.;Kourelhas, K.;Radley, M.;Ambrose, V.;Bradley, M.;Bush, E.;Chavagnon, T.;Chukwurah, B.;Crowley, S.;Dunseath, J.;Emmens, K.;Fletcher, L.;Gordon, J.;Gordon, A.;Hickman, C.;Hill, J.;Ji, M.;Lee, A.;Luker, N.;Norris, S.;Priestley, H.;Sullivan, J.;Taylor, J.;Wintour, J.;Yeung, M.;Youngman, L.;Beebe, S.;Fitzgerald, J.;Godden, J.;Haimes, L.;Lawson, A.;Lochhead, H.;McDonnell, M.;Nash, M.;Taylor, A.;Bennett, A. Taylor;Walton, E.

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降低低密度脂蛋白胆固醇可减少主要血管事件,但更强化的治疗是否安全地产生额外的益处尚不确定。我们的目的是确定更强化的他汀类药物治疗在心血管高危患者中的疗效和安全性。我们对12064名年龄在18-80岁之间有心肌梗死病史的男性和女性进行了一项双盲随机试验。 受试者目前正在接受他汀类药物治疗或有明确的他汀类药物治疗指征,如果已经接受他汀类药物治疗,总胆固醇浓度至少为3.5 mmol/L,如果没有接受他汀类药物治疗,总胆固醇浓度至少为4.5 mmol/L。使用最小化算法集中随机分配至辛伐他汀每日80 mg或20 mg组。参与者在随机化后2、4、8和12个月进行评估,然后每6个月进行一次评估,直到最终随访。主要终点是主要血管事件,定义为冠状动脉死亡、心肌梗死、卒中或动脉血运重建。该研究已注册,编号ISRCTN 74348595。6031名参与者每天分配80 mg辛伐他汀,6033名参与者每天分配20 mg辛伐他汀。在平均6.7年(SD 1.5)的随访中,与20 mg辛伐他汀组相比,80 mg辛伐他汀组LDL胆固醇平均降低0.35(SE 0.01)mmol/L。辛伐他汀80 mg组中1477例(24.5%)受试者发生了主要血管事件,而辛伐他汀20 mg组中1553例(25.7%)受试者发生了主要血管事件,相应的比例降低了6%(风险比0.94,95%CI 0.88 - 1.01; p= 0.10)。出血性卒中(24例[0.4%] vs 25例[0.4%])或血管性(565例[9.4%] vs 572例[9.5%])或非血管性(399例[6.6%] vs 398例[6.6%])死亡的数量无明显差异。与每日服用20 mg辛伐他汀的2例(0.03%)肌病病例相比,80 mg组有53例(0.9%)肌病病例。在我们的试验中,主要血管事件减少6%(SE 3.5%),LDL胆固醇进一步降低0.35 mmol/L,这与以前的试验一致。每日80 mg辛伐他汀可增加肌病,但其他方案可安全地实现LDL胆固醇的强化降低。默克公司;临床试验服务部还接受英国医学研究理事会和英国心脏基金会的资助。
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