Characteristics of trials
| First author (Trial) | Area | Study design | Age, mean (SD) | Gender, n (%) | Comorbidity | Baseline BMI, mean (SD) | Current smoker, n (%) | Type of prevention | Vitamin E dose (source) | Trial duration | Stroke outcomes | ||||
| Intervention | Control | Intervention | Control | Intervention | Control | Intervention | Control | ||||||||
| Belch et al 47 (POPADAD) | Scotland | Double blind randomised controlled trial | 60.5 (10.2) | 60.1 (9.9) | Male, 290 (45.3); Female, 350 (54.7) | Male, 273 (42.9); Female, 363 (57.1) | Diabetes with asymptomatic peripheral arterial disease | 29.7 (2.1) | 29.2 (2.2) | 211 (33.0) | 186 (29.2) | Primary | 200 mg daily (n/a) | Median 6.7 years (4.5–8.6 years) | Total, fatal, non-fatal, ischaemic, haemorrhagic |
| Boaz et al 49 (SPACE) | Israel | Double blind randomised controlled trial | 64.9 (8.3) | 64.4 (8.8) | Male, 67 (69.1); Female, 30 (30.9) | Male, 68 (68.7); Female, 31 (31.3) | Cardiovascular disease with end stage renal disease | Not stated | Not stated | 24 (24.7) | 14 (14.1) | Secondary | 800 IU daily (natural) | Median of 519 days (range 10–763) | Ischaemic |
| Brown et al 41 (HATS) | Canada and USA | Double blind randomised controlled trial | 53 | Male, 139 (87); Female, 21 (13) | Coronary disease and low HDL cholesterol levels | 29 | 38 (24) | Primary | 800 IU daily (natural) | 3 weeks | Ischaemic | ||||
| Catalano et al 39 (CLIPS) | Europe | Double blind randomised controlled trial | 67.1 (8.0) | 64.9 (9.2) | Male, 141 (76.2); Female, 44 (23.8) | Male, 141 (77.9); Female, 40 (22.1) | Peripheral arterial disease | Not stated | Not stated | 51 (27.6) | 44 (24.4) | Primary | 600 mg daily (synthetic) | Mean 20.7±6.4 months | Total, fatal, non-fatal |
| Collaborative Group of the Primary Prevention Project48 (PPP) | Italy | Open label randomised controlled trial | 64.4 (7.6) | 64.4 (7.7) | Male, 937 (42.0); Female, 1294 (58.0) | Male, 975 (43.0); Female, 1289 (57.0) | Hypertension, hypercholesterolaemia, diabetes mellitus or obesity | 27.5 (4.6) | 27.8 (4.7) | 342 (15) | 325 (14) | Primary | 300 mg daily (synthetic) | Mean 3.6 years | Total, fatal, non-fatal |
| Cook et al 52 (WACS) | USA | Double blind randomised controlled trial | 60.6 (8.9) | 60.6 (8.8) | Female, 4083 (100.0) | Female, 4088 (100.0) | History of cardiovascular event or three or more cardiovascular risk factors | 30.3 (6.6) | 30.3 (6.7) | 632 (15.5) | 637 (15.6) | Secondary | 600 IU alternate days (natural) | Mean 9.4 years (8.3–10.1 years) | Total, fatal, non-fatal, ischaemic, haemorrhagic |
| GISSI-Prevenzione Investigators40 (GISSI) | Italy | Open label randomised controlled trial | 59.3 (10.5) | 59.4 (10.6) | Male, 4849 (85.7); Female, 811 (14.3) | Male, 4810 (84.9); Female, 854 (15.1) | Recent (≤3 months) myocardial infarction | 26.6 (3.6) | 26.5 (3.7) | 2384 (42.4) | 2423 (43.1) | Primary | 300 mg daily (synthetic) | 3.5 years | Total stroke |
| Heart Protection Study Collaborative Group43 (HPS) | UK | Double blind randomised controlled trial | 40–70 | Male, 7727 (75.2); Female, 2542 (24.8) | Male, 7727 (75.3); Female, 2540 (24.7) | Substantial 5-year risk of death from coronary heart disease because of a medical history of coronary heart disease, of other occlusive arterial disease, of diabetes mellitus, or of treated hypertension alone | Not stated | Not stated | 1448 (14.1) | 1465 (14.3) | Secondary | 600 mg daily (synthetic) | 18 weeks | Total, fatal, non-fatal, ischaemic, haemorrhagic | |
| Hodis et al 51 (VEAPS) | USA | Double blind randomised controlled trial | 55.7 (9.2) | 56.7 (8.6) | Male, 77 (48); Female 85 (52) | Male, 83 (49); Female 87 (51) | Healthy individuals | Not stated | Not stated | 6 (4) | 5 (3) | Primary | 400 IU daily (synthetic) | Mean 3 years | Total stroke |
| Lamas et al 50 (TACT) | USA and Canada | Double blind randomised controlled trial | 65.3 (3.8) | 65.5 (3.5) | Male, 706 (83.0); Female, 147 (17.0) | Male, 703 (82.0); Female, 152 (18.0) | Myocardial infarction, cardiovascular disease, cardiovascular disease risk factors | 29.3 (2.0) | 30.3 (2.0) | Not stated | Not stated | Secondary | 400 IU daily (natural) | Median 55 months (IQR, 26 to 60 months) | Fatal stroke |
| Lee et al 53 (WHS) | USA | Double blind randomised controlled trial | 54.6 (7.0) | 54.6 (7.0) | Female, 19 937 (100.0) | Female, 19 939 (100.0) | None | 26.0 (5.1) | 26.0 (5.1) | 2590 (13.0) | 2645 (13.3) | Primary | 600 IU on alternate days (natural) | Mean 10.1 years (8.2–10.9 years) | Total, fatal, non-fatal, ischaemic, haemorrhagic |
| Leppala et al 15 (ATBC) | Finland | Double blind randomised controlled trial | 57.7 | 57.7 | Male 14 238 (100.0) | Male 14 281 (100.0) | No history of cancer or serious illness | 26.3 | 26.3 | 14 238 (100.0) | 14 281 (100.0) | Primary | 50 mg daily (synthetic) | Median 6 years | Total, fatal, non-fatal, ischaemic, haemorrhagic |
| Li et al 45 (Linxian) | China | Double blind randomised controlled trial | Median 54 | Male, 730 (44); Female, 927 (56) | Male, 731 (44); Female, 930 (56) | Cytological evidence of oesophageal dysplasia | Not stated | Not stated | 477 (29) | 477 (29) | Primary | 60 IU daily (synthetic) | 6 weeks | Fatal stroke | |
| Milman et al 44 (ICARE) | Israel | Double blind randomised controlled trial | 68.7 (8.1) | 69.5 (8.1) | Male, 344 (47.4); Female, 382 (52.6) | Male, 339 (47.9); Female, 369 (52.1) | Type 2 diabetes with Hp 2–2 genotype | Not stated | Not stated | 82 (11.3) | 89 (12.6) | Secondary | 400 IU daily (natural) | Not stated | Non-fatal stroke |
| Sesso et al 46 (PHS II) | USA | Double blind randomised controlled trial | 64.2 (9.1) | 64.3 (9.2) | Male, 7315 (100.0) | Male, 7326 (100.0) | Cardiovascular disease (myocadiac infarction, stroke) or cancer | 26.0 (3.6) | 26.0 (3.7) | 239 (3.3) | 285 (3.9) | Secondary | 400 IU alternate day (synthetic) | Mean 8 years | Total, fatal, non-fatal, ischaemic, haemorrhagic |
| Steiner et al 54 | USA | Double blind randomised controlled trial | 70.7 (11.6) | 71.4 (10.1) | Male, 22 (42.3); Female, 30 (57.7) | Male, 20 (41.7); Female, 28 (58.3) | Minor stroke or reversible ischaemic neurological deficit, retinal ischaemic event, transient ischaemic attack | Not stated | Not stated | Not stated | Not stated | Secondary | 400 IU daily (n/a) | 2 years | Total stroke, ischaemic, haemorrhagic |
| Stephens et al 38 (CHAOS) | UK | Double blind randomised controlled trial | 61.8 (9.3) | 61.8 (8.9) | Male, 848 (81.9); Female, 187 (18.1) | Male, 842 (87.1); Female, 125 (12.9) | Coronary atherosclerosis | 26.5 (3.5) | 26.4 (3.4) | 149 (14.4) | 121 (12.5) | Primary | 800 IU daily for first 546 patients; 400 IU daily for remainder 489 patients (natural) | Median of 510 days (range 3–981) | Fatal stroke |
| Yusuf et al 42 (HOPE) | USA, Canada, Europe, South America | Double blind randomised controlled trial | 66 (7) | 66 (7) | Male, 3498 (73.5); Female, 1263 (26.5) | Male, 3498 (73.2); Female, 1282 (26.8) | Cardiovascular disease (coronary artery disease, stroke, or peripheral vascular disease) or diabetes with at least one other cardiovascular risk factor (dyslipidaemia, hypertension, microalbuminuria, or current smoking) | 28 (4) | 28 (4) | 665 (14.0) | 679 (14.2) | Secondary | 400 IU daily (natural) | 4–6 years (mean 4.5 years) | Total stroke, haemorrhagic |
ATBC, Alpha-Tocopherol, Beta-Carotene Cancer ; BMI, body mass index; CHAOS, Cambridge Heart Antioxidant Study; CLIPS, Critical Leg Ischaemia Prevention Study; GISSI, Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto miocardico; HATS, HDL-Atherosclerosis Treatment Study; HDL, High-Density Lipoprotein; HOPE, Heart Outcomes Prevention Evaluation; HPS, Heart Protection Study; ICARE, Israel Cardiovascular Atherosclerosis Risk and Vitamin E; PHS II, Physicians’ Health Study II; POPADAD, Prevention of Progression of Arterial Disease and Diabetes; PPP, Primary Prevention Project; SPACE, Secondary Prevention with Antioxidants of Cardiovascular Disease in End Stage Renal Disease; TACT, Trial to Assess Chelation Therapy; VEAPS, Vitamin E Atherosclerosis Prevention Study; WACS, Women’s Antioxidant Cardiovascular Study; WHS, Women’s Health Study.