| Vitamin |
Study, publication
(Jadad score) |
Setting/population |
Treatment
Other medications or nutrients supplemented |
Duration of follow-up; follow-up rate |
Relative Risk (95% Confidence Interval) |
| Restenosis |
Change in Angina |
MI |
CV Events |
CVD Mortality |
All-cause Mortality |
| Vitamin C |
Tomoda
199654
(1) |
119 patients at a single center, Japan, age 35-80 with stable or unstable angina; angiographic evidence of >1 coronary lesion with > 75% diameter; successful coronary angioplasty, no recent MI (<8 weeks), no use of coronary stent, no angioplasty for restenosis. |
Vitamin C 500 mg/day. |
4 months; 85%. |
Vitamin group:
22% of segments
Placebo:
39% of segments
(p<0.05) |
|
|
Vitamin group:
14% required reintervention
Placebo:
33% required reintervention
(p<0.02) |
|
|
| Vitamin E |
Anderson
197445
(4) |
48 Toronto patients from a single center, with stable angina and no change in medication or health status in previous 3 months. |
400 IU/day d-alpha-tocopherol succinate. |
9 weeks; all followed but 25% excluded from analysis. |
|
Improvement in angina in 5/18 (vitamin group) vs. 3/18 (placebo)
(not analyzed) |
|
|
|
|
Gillilan
197746
(3) |
52 patients from a single center in Baltimore, with stable, effort-related angina plus prior MI by Q wave and/or > 75% occlusion of one or more coronary arteries on angiogram. All had ECG evidence of ischemia. Crossover design. |
1600 IU/day d-alpha-tocopherol succinate. |
6 months
92%. |
|
Improvement in angina in 4/48 (vitamin) vs 3/48 (placebo)
p=NS |
|
|
Vitamin group:
2 of 48
Placebo:
2 of 48
p=NS |
|
DeMaio
199247
(2) |
100 patients from one practice in Atlanta with successful angioplasty to reduce restenosis, 84% male. |
1200 IU/day Vitamin E as d-alpha-tocopherol |
4 months; follow-up on 86% of patients completing protocol, unclear how many randomized into trial. |
Vitamin group:
18/52 (34.6%)
Placebo:
24/48 (50%)
p=0.06 |
|
|
|
|
|
CHAOS
Stephens 199648
(4) |
2002 patients from one center in in East Anglia, UK with angiographically-proven coronary artery disease, 84% male. |
800 IU/day vitamin E for the first cohort (n=546), 400 IU/day for the second cohort (n=489). |
Median
1.5 years; 98%. |
|
|
Vitamin group: 14
Placebo: 41
p=0.0001 |
Vitamin group: 41
Placebo: 62
p=0.015 |
Vitamin group: 27
Placebo: 23
p=0.78 |
Vitamin group: 36
Placebo: 26
p=0.31 |
ATBC
Rapola 199744
(4) |
1862 Finnish male smokers age 50-69, with prior MI, no current use of vitamin A, E, or beta-carotene; no severe angina, malignancy, or other serious illness. |
Same as above. |
5-8 years
(median 5.3 years).
Not reported but from national registry. |
|
|
Nonfatal MI:
0.62
(0.41-0.96)
Fatal MI:
1.83
(0.85-3.95)
Total MI:
0.81
(0.56-1.17) |
0.90
(0.67-1.22) |
1.33
(0.86-2.05) |
|
ATBC
Rapola 199843
(4) |
1795 Finnish male smokers age 50-69, with mild angina, no current use of vitamin A, E, or beta-carotene; no severe angina, malignancy, or other serious illness. |
50 IU/day vitamin E and 20 mg/day beta-carotene in 2x2 factorial design. |
5-8 years
48% at 5 years. |
|
Severe angina:
1.14
(0.84-1.53) |
0.83
(0.52-1.34) |
0.95
(0.68-1.33) |
1.08
(0.68-1.72) |
|
GISSI-P
Investigators 199949
(2) |
11,334 patients from multiple centers in Italy with recent (< 3 months) MI. Open label study. |
300 IU/day synthetic alpha tocopherol and 1 gram/day n-3 PUFA in 2x2 factorial design; 2-way analysis. |
3.5 years; 99.9%. |
|
|
|
1.04
(0.88-1.22) |
0.94
(0.81-1.10) |
0.92
(0.82-1.04) |
| Same as above. |
Same as above, 4-way analysis (vitamin E vs. control). |
|
|
|
|
1.02
(0.81-1.28) |
0.80
(0.65-0.99) |
0.86
(0.72-1.02) |
| Beta-carotene |
Physician's Health Study
Gaziano 199041
(4) |
333 US male physicians age 40-84, with chronic stable angina and/or coronary revascularization, no history of cancer, MI, stroke, cerebral ischemia, or noncompliance in run-in phase. |
50 mg beta-carotene on alternate days; cointervention with aspirin in 2x2 factorial design. |
Not reported. |
|
|
|
0.56
(0.31-0.99) |
|
|
Physician's Health Study
Gaziano 199642
(4) |
Same as above. |
Same as above. |
12 years.
Not reported. |
|
|
0.67
(0.36-1.08) |
0.78
(0.50-1.21) |
1.33
(0.78-2.26) |
|
ATBC
Rapola 199744
(4) |
1862 Finnish male smokers age 50-69, with prior MI, no current use of vitamin A, E, or beta-carotene; no severe angina, malignancy, or other serious illness. |
Same as above. |
5-8 years, median 5.3 years.
Not reported but from national registry. |
|
|
Nonfatal MI:
0.67
(0.44-1.02)
Fatal MI:
3.44
(1.70-6.94)
Total MI:
1.11
(0.79-1.56) |
1.11
(0.84-1.48) |
1.75
(1.16-2.64) |
|
ATBC
Rapola 199843
(4) |
1795 Finnish male smokers age 50-69, with mild angina, no current use of vitamin A, E, or beta-carotene; no severe angina, malignancy, or other serious illness. |
20 mg/day beta-carotene and 50 mg/day vitamin E in 2x2 factorial design. |
5-8 years
48% at 5 years. |
|
Severe angina:
1.15
(0.85-1.57) |
0.98
(0.61-1.57) |
1.08
(0.78-1.50) |
1.18
(0.74-1.87) |
|
| Antioxidant combinations |
MVP Study
Tardif 199750
(3) |
255 patients from a single center in Canada with > 50% stenosis, who had successful angioplasty; 77% male. |
60,000 IU beta-carotene, 1000 mg vitamin C, plus 1400 IU alpha-tocopherol daily v. probucol 500 mg/day in 2x2 factorial design. All prescribed AHA Step 1 diet. |
5-7 months; 90%. |
Vitamin group:
40.3% of segments
Placebo:
38.9% of segments
p=0.89 |
|
1 (vitamin group) vs 0 (placebo)
p=NS |
|
|
|
MVP Study
Rodes 199851
(3) |
189 patients from a single center in Canada with angioplasty of coronary artery diameter <3 mm. |
Same as above. |
5-7 months
95%. |
Vitamin group:
45.1% of segments
Placebo:
37.3% of segments
p=0.37 |
|
|
|
|
|
Brown
200152
(4) |
160 Seattle and Canadian patients with clinical coronary disease (prior MI, coronary intervention, or confirmed angina); > 3 coronary stenoses of > 30% or one > 50%; and low HDL and high triglyceride levels. |
800 IU vitamin E, 1000 mg vitamin C, 25 mg natural beta-carotene, plus 100 mg selenium/day; cointervention with Simvastatin 10-20 mg/day plus niacin 2000 mg-4 gm/day in 2x2 factorial design. |
3 years; 91% for angiography, 99% for CV events. |
Vitamin group:
1.8% progression of stenosis
Placebo: 3.9%
progression of stenosis
(p = 0.16) |
|
|
Vitamin group: 21%
Placebo: 24%
(p = NS; exact p value not given) |
|
|
WAVE Trial
Waters 200255
(5) |
423 postmenopausal women in 7 US and Canadian centers with angiographic evidence of >1 coronary artery with 15-75% stenosis. |
400 IU vitamin E plus 500 mg vitamin C daily vs. 0.625 mg conjugated equine estrogens in a 2x2 factorial trial. Women without hysterectomy also received progesterone with estrogen. |
Mean 2.8 years; 79% for angiography; 97% for clinical status. |
Progression of minimal luminal diameter:
Vitamin group:
-0.044 mm/yr
Placebo group:
-0.028 mm/yr
p=0.32 |
|
Vitamin group: 1.9%
Placebo group: 1.9%
p value not cited |
Vitamin group: 6.6%
Placebo group: 3.8%
p value not cited |
Vitamin group: 4.7%
Placebo group: 1.9%
p=0.17 |
Vitamin group: 7.5%
Placebo group: 2.8%
p=0.047 |
| Multi-vitamins |
Schnyder
200153
(4) |
206 patients from multiple centers in Switzerland, Germany, and California, with successful coronary angioplasty of > 1 stenosis of > 50%. |
1 mg folic acid, 400 micrograms vitamin B12, 10 mg pyridoxine daily. |
6 months:
86% for angiography, 96% for clinical outcomes. |
Vitamin group:
19.6%
Placebo:
37.6%
p = 0.01
RR =0.52
(0.32-0.86) |
|
Vitamin group:
4.9%
Placebo:
7.4%
(p = 0.66) |
Vitamin group:
10.8%
Placebo:
22.3%
p =0.047
RR =0.48
(0.25-0.94) |
Vitamin group:
1.0%
Placebo:
2.1%
p = 0.95 |
|
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