| Study, Publication (Jadad Score) |
Setting/population | Treatment (dose, formulation, frequency); Other interventions |
Duration of follow-up; Follow-up rate |
Myocardial Infarction | Cardiovascular Disease Events | Cardiovascular Disease mortality | All-cause mortality | |
|---|---|---|---|---|---|---|---|---|
| Vitamin E | ATBC, ATBC Study Group, 199432 | 29,133 Finnish male smokers age 50-69 with no current use of vitamin A, E, or beta-carotene; no severe angina, malignancy, or other medical problems. | 50 IU/day vitamin E and 20 mg/day beta-carotene in 2x2 factorial design. | 5-8 years, median 6.1 years; case ascertainment essentially complete. | 1.02 (0.95-1.09) |
|||
| ATBC Rapola, 199633 (5) |
Same as above. | See above. | Maximum 7 years, median 4.7 years; 73%. | (Angina) 0.91 (0.83-0.99) |
||||
| ATBC Virtamo, 199834 (5) |
27,271 men, Same as above except patients with prior MI excluded. | See above. | 5-8 years, median 6.1 years; case ascertainment essentially complete. | 1.04 (0.89-1.22) |
0.98 (0.87-1.10) |
0.90 (0.75-1.08) |
||
| HOPE Study Yusuf, 200035 (5) |
9,541 men and women at 129 centers in 19 countries, over age 55, with a history of coronary artery disease, stroke, peripheral vascular disease, or diabetes, plus one cardiovascular risk factor. | 400 IU/day vitamin E from natural sources and ACE inhibitor (10 mg ramipril) in 2x2 factorial design. | 5 years; 99.9%. | 1.02 (0.90-1.15) |
1.05 (0.95-1.22) |
1.05 (0.90-1.22) |
1.00 (0.89-1.13) |
|
| Primary Prevention Project Collaborative Group of the Primary Prevention Project, 200136 (3) |
4,495 Italian men and women attending general practitioner's office or outpatients attending hospital-based hypertension clinic; > age 50 with one of the following cardiovascular risk factors: hypertension, hypercholesterolemia, diabetes mellitus, obesity, family history of early MI (< age 55), or age >64. | 300 IU/day synthetic alpha-tocopherol and 100 mg/day aspirin in 2x2 factorial design. | Mean 3.6 years + 1.0 years; median 4 years 99.3%. | 0.89 (0.52-1.58) |
0.94 (0.77-1.16) |
0.86 (0.49-1.52) |
1.07 (0.77-1.49) |
|
| Vitamin E Atherosclerosis Prevention Study (VEAPS Trial) Hodis, 200239 (5) |
353 subjects >40 years with high LDL and no symptoms or signs of cardiovascular disease; no history of hypertriglyceridemia, diabetes or regular vitamin E. Primary outcome measure was change in carotid artery intima-media thickness. | 400 IU/day tocopherol. | 3 years 73% followed for 3 years. |
Vitamin: 5 Placebo: 4 p value not cited |
Vitamin: 8 Placebo: 10 p=0.81 |
Vitamin: 1 Placebo: 1 p value not cited |
Vitamin: 2 Placebo: 1 p value not cited |
|
| Beta-Carotene | ATBC ATBC Study Group, 199432 (5) |
29,133 Finland male smokers age 50-69 with no current use of vitamin A, E, or beta-carotene; no severe angina, malignancy, or other medical problems. | 20 mg/day beta-carotene and 50 IU/day vitamin E in 2x2 factorial design. | 5-8 years, median 6.1 years; case ascertainment "essentially complete." | 1.08 (1.01-1.16) |
|||
| ATBC Rapola, 199633 (5) |
Same as above. | Same as above. | Maximum 7 years, median 4.7 years; 73%. | (Angina) 1.06 (0.97-1.16) |
||||
| ATBC Virtamo, 199834 (5) |
27,271 men, Same as above except patients with prior MI excluded. | Same as above. | 5-8 years, median 6.1 years; case ascertainment "essentially complete." | 1.06 (0.90-1.24) |
1.03 (0.91-1.16) |
0.99 (0.83-1.19) |
||
| Physician's Health Study Hennekens, 199629 (4) |
22,071 US male physicians age 40-84, with no history of cancer, MI, stroke, or cerebral ischemia. | 50 mg beta-carotene on alternate days; cointervention with 325 mg aspirin in 2x2 factorial design. | Mean 12 years; 99.99%. | 0.96 (0.84-1.09) |
1.0 (0.91-1.09) |
1.09 (0.93-1.27) |
1.02 (0.93-1.11) |
|
| Skin Cancer Prevention Study Greenberg, 199631 (3) |
1,188 US men and 532 women with prior non-melanoma skin cancer, < age 85. Multicenter trial to prevent skin cancer recurrence. | 50 mg/day beta-carotene. | Median 8.2 years; 98%. | 1.16 (0.82-1.64) |
1.03 (0.82-1.30) |
|||
| Women's Health Study I-M Lee, 199930 (4) |
39,876 US female health professionals, > age 45; no history of cancer, coronary heart disease, or cerebrovascular disease. | 50 mg beta-carotene on alternate days; co-intervention with 100 mg aspirin and 600 IU/day vitamin E in 2x2x2 factorial design. | Median 2.1 years of treatment plus 2 years of follow-up; 100%. | 0.84 (0.56-1.27) |
1.14 (0.87-1.49) |
1.17 (0.54-2.53) |
1.07 (0.74-1.56) |
|
| CARET Omenn, 199637 (4) |
4,060 West Coast US male asbestos workers, age 45-74, first exposure to asbestos >15 yrs ago, plus asbestos-related lung disease or high-risk job for 5 years, and 14,254 US male and female heavy smokers age 50-69, >20 pack-years, current smokers or quit <6 years ago. | 30 mg/day beta-carotene and 25,000 IU/day retinol (retinyl palmitate). | 5.5 years; 98% for mortality. | 1.26 (0.99-1.61) | 1.17 (1.03-1.33) | |||
| AREDS AREDS Study Group, 200138 (5) |
4,757 US participants, age 55-80 years recruited from ophthalmology clinics, without major cardiovascular disease or cancer in recent past. | 500 mg vitamin C, 400 IU vitamin E, 15 mg beta-carotene per day. Some patients with age-related macular degeneration also assigned to receive 80 mg zinc and 2 mg copper versus placebo. 66% of the cohort chose to take a multivitamin (Centrum*) in addition. | Mean 6.3 years 97.7% completed the trial. |
Reported chest pain: Vitamins: 19.8% Placebo: 22.8% (p=0.01) |
1.06 (0.84-1.33) |
|||
| Heart Protection Study Heart Protection Collaborative Group, 200240 (5) |
20,536 adults 40-80 years in UK with blood cholesterol >3.5 mmol/L and history of coronary artery disease, other occlusive arterial disease, diabetes, or treated hypertension; excluded with prior high dose vitamin E supplementation or life-threatening disease. Must have shown compliance in 2 month prerandomization compliance period. | 600 mg synthetic vitamin E, 250 mg vitamin C and 20 mg beta-carotene daily in 2x2 factorial trial. Cointervention with simvastatin. | 5 years; 99.7% followed for morbidity. | (Vascular Mortality) 1.05 (0.95-1.15) |
1.04 (0.97-1.12) |
Note: ATBC indicates Alpha-Tocopheral Beta-Carotene; MI, myocardial infarction; CARET, Carotene and Retinol Efficacy Trial; HOPE, Heart Outcomes Prevention Evaluation; LDL, low-density lipoprotein; RR= relative risk.
*Wyeth Consumer Healthcare, Berks, United Kingdom.