| Trial | control | p<0.05 | harm | NS |
|---|
| ATBC vitamin E, 1994 | vitamin E vs placebo | Ischemic Stroke 0.86 [0.75; 0.99] | | cardiovascular death 0.98 [0.89; 1.07] Hemorrhagic Stroke 1.22 [0.92; 1.61] all-cause cerebrovascular accident 0.93 [0.83; 1.05] Cardiovascular Event 0.98 [0.89; 1.07] |
| CHAOS, 1996 | vitamin E vs placebo | non fatla MI 0.32 [0.18; 0.58] Cardiovascular Event 0.60 [0.41; 0.88] | | all-cause mortality 1.29 [0.79; 2.13] cardiovascular death 1.10 [0.63; 1.90] |
| GISSI, 1999 | vitamin E vs control | | | all-cause mortality 0.92 [0.82; 1.04] cardiovascular death 0.94 [0.81; 1.10] non fatal stroke 0.87 [0.65; 1.17] non fatla MI 1.11 [0.92; 1.33] all-cause cerebrovascular accident 0.87 [0.65; 1.17] Cardiovascular Event 0.98 [0.88; 1.09] |
| HOPE, 2000 | vitamin E vs placebo | | | cardiovascular death 1.05 [0.90; 1.21] Hemorrhagic Stroke 1.31 [0.64; 2.70] non fatal stroke 1.17 [0.96; 1.42] non fatla MI 1.02 [0.91; 1.14] Ischemic Stroke 1.15 [0.94; 1.41] all-cause cerebrovascular accident 1.17 [0.96; 1.42] Cardiovascular Event 1.05 [0.96; 1.15] |
| AREDS, 2001 | vitamin E vs placebo | | | all-cause mortality 1.05 [0.89; 1.25] |
| PPP, 2001 | vitamin E vs control | | | all-cause mortality 1.07 [0.78; 1.49] coronary events 0.89 [0.51; 1.58] cardiovascular death 0.86 [0.49; 1.51] Hemorrhagic Stroke ∞ [NaN; ∞] non fatal stroke 1.56 [0.78; 3.13] non fatla MI 1.07 [0.56; 2.04] Ischemic Stroke 1.13 [0.60; 2.13] all-cause cerebrovascular accident 1.24 [0.67; 2.31] Cardiovascular Event 1.07 [0.74; 1.55] |
| SPACE, 2000 | vitamin E vs placebo | coronary events 0.45 [0.21; 0.99] Cardiovascular Event 0.54 [0.33; 0.89] | | all-cause mortality 1.09 [0.72; 1.66] cardiovascular death 0.61 [0.28; 1.33] Ischemic Stroke 0.85 [0.27; 2.70] all-cause cerebrovascular accident 0.85 [0.27; 2.70] |
| Linxian, 1993 | vitamin E vs placebo | | | Cardiovascular Event 0.91 [0.77; 1.08] |
| WACS vitamin E, 2007 | vitamin E vs placebo | | | all-cause mortality 1.02 [0.91; 1.15] coronary events 0.92 [0.73; 1.16] cardiovascular death 0.96 [0.79; 1.16] Hemorrhagic Stroke 1.50 [0.68; 3.34] non fatal stroke 0.82 [0.64; 1.04] non fatla MI 0.89 [0.69; 1.14] Ischemic Stroke 0.81 [0.64; 1.02] all-cause cerebrovascular accident 0.85 [0.68; 1.07] Cardiovascular Event 0.92 [0.81; 1.04] |
| PHS II vitamin E, 2008 | vitamin E vs placebo | | Hemorrhagic Stroke 1.70 [1.02; 2.84] | all-cause mortality 1.03 [0.94; 1.12] cardiovascular death 1.03 [0.87; 1.22] Ischemic Stroke 0.98 [0.80; 1.19] all-cause cerebrovascular accident 1.05 [0.87; 1.25] Cardiovascular Event 0.99 [0.89; 1.10] |
| WHS vitamin E, 2005 | vitamin E vs placebo | | | Hemorrhagic Stroke 0.92 [0.61; 1.38] Ischemic Stroke 0.98 [0.81; 1.20] all-cause cerebrovascular accident 0.98 [0.82; 1.17] |
| HOPE renal insufficiency subgroup, 2004 | vitamin E vs placebo | | | all-cause mortality 0.90 [0.69; 1.18] coronary events 0.97 [0.73; 1.28] cardiovascular death 0.99 [0.70; 1.40] all-cause cerebrovascular accident 1.03 [0.60; 1.76] Cardiovascular Event 1.04 [0.83; 1.32] |
| ASAP, 2000 | vitamin E vs placebo | | | all-cause mortality 2.00 [0.37; 10.82] |
| ATBC 2nd prev subgroup (vitamin E), 1998 | vitamin E vs placebo | | | coronary death 1.06 [0.79; 1.41] coronary events 0.94 [0.77; 1.14] non fatla MI 0.81 [0.60; 1.11] |
| Trial | Treatments | Patients | Method |
|---|
| ATBC vitamin E, 1994 | vitamin E (alpha-tocopherol) 50mg/d
(n=14564) vs. placebo
(n=14569) factorial design of four regimens: alpha-tocopherol (50 mg per day) alone, beta carotene (20 mg per day) alone, both alpha-tocopherol and beta carotene, or placebo
| male smokers 50 to 69 years of age from southwestern Finland
| double-blind Factorial plan Sample size: 14564/14569 Primary endpoint: not defined FU duration: 6.1 median (range 5-8y)
|
| CHAOS, 1996 | vitamin E 400-800UI/d (alpha tocopherol) (n=1035) vs. identical placebo (n=967) | patients with angiographically proven coronary atherosclerosis | double-blind Parallel groups Sample size: 1035/967 Primary endpoint: CV death, MI and non fatal MI alone FU duration: 1.5y 2 primary endpoints but no procedure to control multiplicity |
| GISSI, 1999 | vitamin E 300mg/d (n=5660) vs. no vitamine E (n=5664) randomization between 4 treatment: n-3 PUFA (1 g daily), vitamin E (300 mg daily), both
or none (control) | patients with recent (3 months) myocardial
infarction | open Factorial plan Sample size: 5660/5664 Primary endpoint: death, MI, stroke FU duration: 3.5y |
| HOPE, 2000 | vitamin E 400IU/d from natural sources (n=4761) vs. matching placebo (n=4780) factorial design of ramipril and vitamin E | women and men 55 years of age or older who were at high risk for cardiovascular events because they had cardiovascular disease or diabetes in addition to one other risk factor. | double-blind Factorial plan Sample size: 4761/4780 Primary endpoint: CV death, MI, stroke FU duration: 4.5y |
| AREDS, 2001 | daily supplementation of antioxidants (500 mg of vitamin C, 400 IU of vitamin E, and 15 mg of beta carotene) (n=2370) vs. placebo (n=2387) patients with more than a few small drusen were also randomly assigned to receive tablets with or without zinc (80 mg of zinc as zinc oxide) and copper (2 mg of copper as cupric oxide) as part of the age-related macular degeneration trial | patients with age-related lens opacities and visual acuity loss | double-blind Factorial plan Sample size: 2370/2387 Primary endpoint: opacity grades or cataract surgery FU duration: 6.3 y |
| PPP, 2001 | vitamin E (300 mg/day) (n=2231) vs. no vitamin E (n=2264) factorial design with aspirin | men and women
aged 50 years or greater, with at least one of the major
recognised cardiovascular risk factors | open Factorial plan Sample size: 2231/2264 Primary endpoint: CV events FU duration: 3.6y |
| SPACE, 2000 | vitamin E 800 IU daily (n=97) vs. matching placebo (n=99) | Haemodialysis patients aged 40–75 years with pre-existing cardiovascular disease | double -blind Parallel groups Sample size: 97/99 Primary endpoint: MI, stroke, PVD, unstable angina FU duration: 1.42 years |
| Linxian, 1993 | beta carotene, vitamin E, and selenium (n=14792) vs. (n=14792) | Apparently healthy Individuals of ages 40-69 | Sample size: 14792/14792 Primary endpoint: FU duration: 5y |
| WACS vitamin E, 2007 | vitamin E (600IU every two days)
(n=4083) vs. placebo
(n=4088) 2x2x2 factorial design testing the effects of ascorbic acid (500 mg/d), vitamin
E (600 IU every other day), and beta carotene (50 mg
every 2day)
| female health professionals at increased
risk (40 years or older with a history of CVD or 3 or more CVD
risk factors)
| double blind Factorial plan Sample size: 4083/4088 Primary endpoint: MI, stroke, coronary revascularization, CVD death FU duration: 9.4 years
|
| PHS II vitamin E, 2008 | vitamin E 400IU every two days
(n=7315) vs. placebo
(n=7326) factorial trial evaluating vitamin E (400 IU every 2 days synthetic alpha-tocopherol), vitaminC(500mg synthetic ascorbic acid), a multivitamin (Centrum Silver daily; Wyeth Pharmaceuticals) and beta carotene (50mg, Lurotin on alternate days) | US male physicians aged 50 years or older 7641 partcipant from PHS I and 7000 new physicians
| double blind Sample size: 7315/7326 Primary endpoint: Cv death, MI, Stroke FU duration: 8 years (mean)
|
| WHS vitamin E, 2005 | vitamin E 600 IU every other day (á-tocopherol) (n=19937) vs. placebo (n=19939) factorial design vitamin E or placebo and aspirin or placebo | apparently healthy US women aged at least 45 years | double-blind Factorial plan Sample size: 19937/19939 Primary endpoint: major cardiovascular event FU duration: 10.1 y two primary endpoint specified without method for dealing with multiplicity |
| HOPE renal insufficiency subgroup, 2004 | vitamin E 400 IU/day, natural (n=499) vs. placebo (n=494) | patients with either known cardiovascular disease or diabetes and at least one additional coronary risk factor and renal insufficiency (sub group) | double-blind Factorial plan Sample size: 499/494 Primary endpoint: not defined FU duration: 4.5y subgroup analysis |
| ASAP, 2000 | d-alpha-tocopherol 91 mg (136 IU) twice daily (n=260) vs. placebo (n=260) | smoking and nonsmoking men and postmenopausal women aged 45-69 years with serum cholesterol >= 5.0 mmol/l | double-blind Factorial plan Sample size: 260/260 Primary endpoint: carotid artery mean intima-media thickness FU duration: 3 years after the
double-blind 3-year period, the study was continued for another 3
years as an open study |
| ATBC 2nd prev subgroup (vitamin E), 1998 | alpha tocopherol (vitamin E)
50 mg/day (n=916) vs. placebo (n=879) factorial design of alpha tocopherol (vitamin E)
50 mg/day and beta carotene 20 mg/day | patients enroled in the ATBC trial and
who had angina pectoris in the Rose chest
pain questionnaire at baseline | double-blind Factorial plan Sample size: 916/879 Primary endpoint: not defined FU duration: 3.79 y |
