MRC BHFHeart Protection Study of cholesterol-lowering therapy and of antioxidant vitamin supplementation in a wide range of patients at increased risk of coronary heart disease death: early safety and efficacy experience

Meade, T Sleight, P Collins, R Armitage, J Parish, S Peto, R Youngman, L Buxton, M de Bono, D Fuller, J Keech, A Mansfield, A Pentecost, B Simpson, D Warlow, C O'Toole, L Doll, R Wilhelmsen, L Fox, K Hill, C Sandercock, P Barton, J Bray, C Jayne, K Lawson, A Harding, P Lay, M Wallendszus, K Benjamin, N Webster, J Jamieson, J Donald, L Blandford, R Carrington, L McMahon, H Cheetham, D Reckless, J Brice, L Carpenter, R Christmas, J Flower, C Cooper, I Frampton, S Pickerell, E Wells, J Scott, M Crowe, V Shaw, A Shannon, L Jones, S Faulkner, G Lavery, A O'Leary, H Watson, R Capewell, C Hughes, S Bain, S Jones, A Holmes, G Jewkes, C Bellamy, T Harrison, P Buller, N Nield, H Smith, E Vint, P Crook, P Williams, J Bateson, M Cawley, P Gill, P Simpson, K Armitage, M Cope, C Tricksey, J Wilson, M Cottrell, S Jones, C Llewellyn, M Smith, P Woodsford, T Vincent, R Joyce, E Skipper, N Peters, P Lemon, M Stansbie, D Kidan, AH Halestrap, M Gibbons, A Meredith, J Dawkins, C Papouchado, M Baker, L Boulton, K Dawe, C Lewis, A Wisby, J Brown, M Emeny, J Smith, W Trutwein, D Cornwell, M Lloyd, D White, C Khalifa, M MacKereth, N Martin, G Baxter, M Chambers, R Glenn, S Kerr, J Golesworthy, G Watts, A Baines, G Groom, J Price, L Barlow, I Mallya, S Lewis, S Maiden, J Nash, M Lowe, V Scott, A Cozens, S Hannah, J Hinwood, M Millward, J Murphy, J Charters, M Graham, B Banks, M Nobbs, R Kemp, T Turner, P Sheldrake, S Labib, M Pearson, R Sidaway, J Davies, P Hodgkiss, M MacLeod, D Stuart, R Albrock, J Fisher, J Stuart, F Swainson, C Glenn, S Johnston, J Sadler, S Curren, M Feirnie, S Stenhouse, L Lindley, R Warlow, C Kenny, A Waddell, F Brownlie, M Guilar, I Marshall, A Went, J Clarke, S Inman, A Simmonds, J Duook, B Mortimore, G Pascoe, A Cobbe, S Campbell, C Young, H Keeble, M Absalom, S Bracey, N Falco, L Stone, D Tildesley, G Carr, B Longstaff, G Turner, A Wilkinson, H Wilkinson, S Hillson, R Brookes, D Capper, B Price, K Badrick, V Griffiths, H Fitzgerald, J Lewis, S Campbell, P Baines, G Claypole, G Lomas, J Rogers, A Brown, A Cheshire, J Rowley, J Ball, S Prentice, C Hall, A Atha, P Caffrey, K Currie, W Hague, C Hall, S Maguire, P Rose, C Watson, R Buxton, A Wedgwood, A Gilbey, S Currie, W Drury, K Hall, S Rose, C Wilson, J Vaughn, M Humphrey, P Blocksage, J McSloy, R Ost, K Owen, L Saminaden, S Watling, D Wiseman, J Davies, J Kehely, A Kooner, J Capper, B Corbett, I Peters, J Price, K Van Goethem, M Chambers, J Crawshaw, M O'Sullivan, J Powell, S Reoch, M Sanders, J Beament, MF Fangrad, B Williams, Y Banim, S Crake, T Ford, B Glynn, V Ismail, S Buller, N Coats, A Aitken, L Cruddas, E Serup-Hansen, K Nosworthy, D Reilly, N Coppack, S Clifton, P Holmes, A Camplin, L Travill, C Gent, S Hunter, A Stroud, C Griffiths, K Davies, E Mason, M Robinson, A Belfield, S Chambers, J Bispham, L Mercer, A Sheppard, J Burrage, S Cruickshank, K Chan, KL Wharfe, V Woodward, J Alexander, F Williams, Y Walker, M Thomas, P Day, J Edwards, S Nicholson, P Gleeson, S Savage, M Swan, J McSorland, D Waywell, C O'Neill, C Wharton, L Adams, P Lindley, R Cartilidge, N Mace, M Thompson, M Hulmes, J Armitage, J Collins, R Sleight, P Beebe, S Campbell, M Fitzgerald, J Goodwin, S Lawson, A Lochhead, H Whitbread, P Knight, S Taylor, A Booker, V Brooker, R Bruce, N Cody, A Corbett, M Crowther, J Greenlaw, R Hauer, B Heineman, J Hope, C Indge, C Jones, R Jones, S King, M Lang, H McCabe, P Monaghan, H Murphy, K Owers, A Peto, C Pickworth, S Radley, A Rowe, A Southren, S Wilson, S Wincott, E Youngman, L Buckingham, L Burton, M Chukwarah, B Clark, S Colominas, C Crowley, S Edwards, S Hill, J Kourellias, K Lennon, C McAteer, M Miller, N Radley, M Taylor, J Baigent, C Chen, Z Clarke, R Sudlow, C Findlay, I Campbell, C Hunter, J Young, H McNally, E Crowe, P Crowe, V Hunter, B Shaw, A Shannon, L Curless, R Lindley, R McKenna, P Roberts, S Black, A Martin, J Burt, M O'Donnell, J Marsh, S Woodward, J O'Hare, R Owen, C McLeod, A Richardson, M Reeves, C Mallya, R Forshaw, J Hodson, J Lenden, H Osborn, G Barren, J Ballard, A Docherty, B McDonnell, M Ritson, S Tyler, D Carter, S Rigney, C Wray, R Gaughan, K Sinclair, J Burleigh, J McDonald, J Venables, G Doyle, C Fox, M Mundey, L Strafford, S Lloyd-Mostyn, R Bailey, D McKenzie, I Bamford, R Thomas, P Thomas, R Alexander, C Chohan, R Wood, K Capps, N Stiles, C Tonks, L Crank, S Cunnington, A Giles, P Groves, N Walton, E Dance, W Clements, M Feben, C Hunter, A Walker, E Atkins, L Williats, R Hughes, E Sidaway, J Sumara, S Banks, G Glover, R Hall, K Munro, A Pycock, C Tibbutt, D Cadwell, J Greenwood, M Betts, M Signy, M Joyce, E Wrapson, C McCourt, G Moore, R Price, S Regan, R Aldersley, M Pendry, P
T. Meade et al., MRC BHFHeart Protection Study of cholesterol-lowering therapy and of antioxidant vitamin supplementation in a wide range of patients at increased risk of coronary heart disease death: early safety and efficacy experience, EUR HEART J, 20(10), 1999, pp. 725-741
Citations number
Categorie Soggetti
Cardiovascular & Respiratory Systems
Journal title
ISSN journal
0195-668X → ACNP
Year of publication
725 - 741
SICI code
Aims In observational studies, prolonged lower blood total cholesterol leve ls - down at least to 3 mmol . l(-1) - are associated with lower risks of c oronary heart disease. Cholesterol-lowering therapy may, therefore, be wort hwhile for individuals at high risk of coronary heart disease events irresp ective of their presenting cholesterol levels. Observational studies also s uggest that increased dietary intake of antioxidant vitamins may be associa ted with lower risks of coronary heart disease. The present randomized tria l aims to assess reliably the effects on mortality and major morbidity of c holesterol-lowering therapy and of antioxidant vitamin supplementation in a wide range of different categories of high-risk patients. Methods and Results Men and women aged 40 to 80 years were eligible provide d they were considered to be at elevated risk of coronary heart disease dea th because of past history of myocardial infarction or other coronary heart disease, occlusive disease of non-coronary arteries, diabetes mellitus or treated hypertension; had baseline blood total cholesterol of 3.5 nmol . l( -1) or greater and no clear indications for, or contraindications to, eithe r of the study treatments. Eligible patients who completed a pre-randomizat ion run-in phase on active treatment were randomly allocated to receive sim vastatin (40 mg daily) or matching placebo tablets and, in a '2 x 2 factori al' design: antioxidant vitamins (600 mg vitamin E, 250 mg vitamin C and 20 mg beta-carotene daily) or matching placebo capsules. Follow-up visits aft er randomization are scheduled at 4, 8 and 12 months, and then 6-monthly, f or at least 5 years. Between July 1994 and May 1997, 15 454 men and 5082 women were randomized, with 9515 aged over 65 years at entry. Diagnostic criteria overlapped, with 8510 (41%) having had myocardial infarction (most of whom were either fema le, or elderly or with low blood cholesterol), 4869 (24%) some other histor y of coronary heart disease, 3288 (16%) cerebrovascular disease, 6748 (33%) peripheral vascular disease? 5963 (29%) diabetes mellitus (of whom 3985 ha d no history of coronary heart disease) and 8455 (41%) treated hypertension . Baseline non-fasting total cholesterol levels were less than 5.5 mmol . l (-1) in 7882 (38%) participants. and LDL (low density lipoprotein) choleste rol less than 3.0 mmol . l(-1) in 6888 (34%). During a mean follow-up of 25 months (range: 13 to 47 months), no significa nt differences had been observed between the treatment groups in the number s of patients with muscle symptoms, other possible side-effects leading to termination of study treatment, or elevated liver and muscle enzymes. After 30 months of follow-up, 81% of randomized patients remained compliant with taking their study simvastatin or placebo tablets, and allocation to simva statin produced average reductions in non-fasting blood total and LDL chole sterol of about 1.5-1.6 mmol . l(-1) and 1.1-1.2 mmol . l(-1) respectively. Eighty-seven per cent of patients remained compliant with taking their vit amin or placebo capsules, and allocation to the vitamin supplement produced an average increase in plasma vitamin E levels of about 24 mu mol . l(-1). Based on this initial follow-up period, the estimated annual rate of non-f atal myocardial infarction or fatal coronary heart disease is 2.4%, annual stroke rate is 1.3%. and annual all-cause mortality rate is 2.2%. Conclusion The Heart Protection Study is large, it has included a wide rang e of patients at high risk of vascular events, and the treatment regimens b eing studied are well-tolerated and produce substantial effects on blood li pid and vitamin levels. The study should, therefore, provide reliable evide nce about the effects of cholesterol-lowering therapy and of antioxidant vi tamin supplements on all-cause or cause-specific mortality and major morbid ity in a range of different categories of individuals for whom uncertainty remains about the balance of benefits and risks of these treatments.