TABLE 1.
Prospective studies assessing vitamin E for cardiovascular protection
| Trial | Intervention | Follow-up (years) | Specific Patient Characteristics | Number of Patients | Clinical Outcomes |
| Studies assessing vitamin E for primary prevention [Results are given in relative measures (95% CI) or absolute numbers (P value)] | |||||
| Virtamo et al. (36) | α-tocopherol (50 mg/day), β carotene (20 mg/day), both, or placebo | 6.1 | Male, smokers | 27,271 | First MI and CV death: |
| RR 0.98 (0.87–1.10) | |||||
| PPP (37) | Aspirin (100 mg/day) and α-tocopherol (300 mg/day) (2 × 2 design) | 3.6 | Over 1 CV risk factor | 4,495 | CV death, MI, stroke: |
| RR 1·07 (0.74–1.56) | |||||
| St. Francis (39) | Atorvastatin (20 mg/day) plus vitamin C (1 g/day) plus α-tocopherol (1,000 IU/day) versus placebo | 4.3 | CCS ≥ 80th percentile | 1,005 | ASCVD event rate: |
| −6.9% versus 9.9% (P = 0.08) | |||||
| VEAPS (40) | DL-α-tocopherol (400 IU/day) or placebo | 3 | LDL > 3.37 mmol/l | 353 | CC-IMT change from baseline: |
| −0.0023 ± 0.0007 versus 0.0040 ± 0.0007 (P = 0.08) | |||||
| ATIC (41) | α-tocopherol, pravastatin, and homocysteine-lowering therapy, consecutively introduced | 1.5 | CKD | 93 | CC-IMT, ED, renal function, and albuminuria: |
| CC-IMT: 0.68–0.63 mm versus 0.65–0.71 mm (P < 0.001) | |||||
| BA-FMD: 4.66–7.56% versus 6.21–4.73% (P < 0.001) | |||||
| eGFR: 32–35 ml/min/1.73 m2 versus 35–33 ml/min/1.73 m2 (P = 0.89) | |||||
| Urinary albumin excretion: 34% (3–44%) reduction | |||||
| WHS (42, 43) | α-tocopherol (600 IU), aspirin, or placebo | 10.1 | Women | 39,876 | CV death, MI, stroke: |
| RR 0.93 (0.82–1.05) | |||||
| Cancer: | |||||
| RR 1.01 (0.94–1.08) | |||||
| Heart failure: | |||||
| HR 0.93 (0.71–1.21) | |||||
| PHS II (44) | α-tocopherol (400 IU every other day), vitamin C, or placebo | 8 | Men | 14,641 | CV death, MI, stroke: |
| HR 1.01 (0.90–1.13) | |||||
| Studies assessing vitamin E for secondary prevention [Results are given in relative measures (95% CI) or absolute numbers (P value)] | |||||
| DeMaio et al. (45) | DL-α-tocopherol (1,200 IU/day) or placebo | 0.33 | — | 100 | Restenosis: |
| −34.6% versus 50% (P = 0.06) | |||||
| CHAOS (46) | DL-α-tocopherol (400 IU/day or 800 IU/d) or placebo | 1.4 | — | 2,002 | CV death and nonfatal MI: |
| RR 0.53 (0.34–0.83) | |||||
| GISSI-Prevenzione (47) | PUFA (1 g/day), DL-α-tocopherol (300 mg/day), both, or none | 3.5 | — | 5,658 | Death, MI, and stroke: |
| RR 0.95 (0.86–1.05) | |||||
| HOPE (48) | α-tocopherol (400 IU/day), ACE inhibitor, or placebo (2 × 2 design) | 4.5 | — | 9,541 | CV death, MI, and stroke: |
| RR 1.05 (0.95–1.16) | |||||
| WAVE (52) | Vitamin E (400 IU/day) plus vitamin C (500 mg BID), HRT, or placebo (2 × 2 design) | 4 | Postmenop ausal women | 423 | Death, MI, stroke: |
| HR 1.5 (0.80–2.9) | |||||
| Heart Protection Study (53) | DL-α-tocopherol (600 mg/day), vitamin C (250 mg/day), and β-carotene (20 mg/day) or placebo | 5 | — | 20,536 | CV death, MI, stroke, revascularization: |
| RR 1.00 (0.94–1.06) | |||||
| Cancer: | |||||
| RR 0.98 (0.89–1.08) | |||||
| SPACE (54) | α-tocopherol (800 IU/day) or placebo | 1.4 | Hemodialysis | 196 | MI, ischemic stroke, peripheral vascular disease, and unstable angina: |
| RR 0.46 (0.27–0.78) | |||||
| Longitudinal studies assessing CV outcomes according to Hp phenotype in patients with DM [Results are given in relative measures (95% CI) or percentages (P value)] | |||||
| Strong Heart Study (66) | — | 6 | Native Americans | 412 | CV events: |
| OR Hp 2-2 versus 1-1: 5.08 (2.37–10.89) | |||||
| OR Hp 2-2 versus 2-1: 3.26 (1.67–6.37) | |||||
| Burbea et al. (71) | — | 3 | Hemodialysis | 392 | 3 years survival rate: |
| Hp 2-2 45.1% versus Hp non-2-2 50% (P < 0.003) | |||||
| Costacou et al. (76) | — | 18 | CV disease free, type 1 diabetics | 453 | Angina, ischemic ECG, MI, angiographic stenosis >50%, or revascularization: |
| HR Hp 2-2 versus Hp 1-1: 2.21 (1.05–4.65) | |||||
| Roguinet al (70). | — | 1 | Post PTCA | 935 | Total MI, total mortality, target vessel revascularization, MACE (combination of all): |
| Hp 2-2, 31.4%; Hp 1-1, 20.9%; Hp 2-1, 26.4% (P = 0.015) | |||||
| Suleiman et al. (72) | — | 30 days | Acute MI | 506 | 30 days mortality + heart failure: |
| OR Hp 1-1 versus Hp 2-2: 0.35 (0.15–0.86) | |||||
| Longitudinal studies assessing CV outcomes according to Hp phenotype with and without vitamin E treatment [Results are given in relative measures (95% CI)] | |||||
| WHS study data (42, 68) | α-tocopherol (600 IU), aspirin, or placebo | 10.1 | Women | 721 | CV death, MI, stroke: |
| OR in Hp 2-2, 0.87 (0.49, 1.53) | |||||
| OR in Hp non-2-2, 1.33 (0.75, 2.37) | |||||
| ICARE (67) | D-α-tocopherol (400 IU/day) or placebo | 1.5 | — | 2,967 | CV death, MI, stroke: |
| OR in Hp 2-2, 0.46 (0.25, 0.85) | |||||
| HOPE study data (48, 69) | Vitamin E (400 IU/day), ACE inhibitor, or placebo (2 × 2 design) | 4.5 | — | 530 | CV death, MI, stroke: |
| OR in Hp 2-2, 0.69 (0.42, 1.13) | |||||
| OR in non-Hp 2-2, 1.02 (0.69, 1.50) | |||||
ASCVD, atherosclerotic cardiovascular disease (events includes coronary death, nonfatal MI, coronary revascularization procedures, nonhemorrhagic stroke, and peripheral revascularization procedures); BA-FMD, brachial artery flow-mediated dilatation; CC-IMT, common carotid intima-media thickness; CCS, coronary calcium score; CKD, chronic kidney disease; ED, endothelial dysfunction; ECG, electrocardiogram; MACE, major adverse cardiac events.