Table 4.

Randomized controlled trials demonstrating no effect of antioxidant therapy.

Source	Number of patients	Inclusion criteria	Antioxidant agent	Dose	Route	Endpoints	Followup	Events
Virtamo et al. [111]	27271	Male smokers	Vit E, beta-carotene	50 mg, 20 mg	PO	Major coronary events (CV death, MI)	6.1 y	CV events: Vit E 519, beta-carotene 547, Vit E + beta-carotene 511, and pl 534; CV death: Vit E 212, beta-carotene 235, Vit E + beta-carotene 222, and pl 238; non-fatal MI: Vit E 307, beta-carotene 312, Vit E + beta-carotene 289, and pl 296
Rapola et al. [112]	1862	Previous MI	Vit E, beta-carotene	50 mg, 20 mg	PO	Major coronary events (CV death, MI)	5.3 y	CV events: Vit E 94, beta-carotene 113, Vit E + beta-carotene 123, and pl 94
HATS [113]	80	CAD	Vit E/C, beta-carotene, and selenium	800 IU, 1 g, 25 mg, and 100 g	PO	Composite endpoint (CV death, MI, and PTCA/CABG)	38 m	CV events: antiox 9, pl 9; CV death: antiox 0, pl 1; nonfatal MI: antiox 1, pl 4
PHS II [114]	14641	Male physicians	Vit E/C	400 IU 500 mg	PO	Composite endpoint (CV death, MI, and stroke)	8 y	CV events: Vit E 620, pl 625; Vit C 619, pl 626; CV death: Vit E 258, pl 251; Vit C 256, pl 253; MI: Vit E 240, pl 271; Vit C 260, pl 251
WACS [115]	8171	High CV risk women	Vit E/C, beta-carotene	600 IU q48 h, 500 mg, and 50 mg q48 h	PO	Composite endpoint (CV death, MI, PTCA/CABG, and stroke)	9.4 y	CV events: Vit E 708, pl 742; Vit C 731, pl 719; beta-carotene 731, pl 719; CV death: Vit E 193, pl 202; Vit C 206, pl 189; beta-carotene 211, pl 184; MI: Vit E 131, pl 143; Vit C 140, pl 134; beta-carotene 135, pl 139
PPP [116]	4495	Subjects ≥ 1 RF	Vit E	300 mg	PO	Composite endpoint (CV death, MI, and stroke)	3.6 y	CV events: Vit E 56, pl 53; CV death: Vit E 22, pl 26; MI: Vit E 22, pl 25
GISSI-prevenzione [117]	5660	Recent MI	Vit E	300 mg	PO	Composite endpoint (CV death, MI, and stroke)	3.5 y	CV events: Vit E 371, pl 414; CV death: Vit E 155, pl 193; MI: Vit E 22, pl 25
Greenberg et al. [118]	1720	Skin cancer	beta-carotene	50 mg	PO	CV death	4.3 y	CV death: beta-carotene 68, pl 59
PHS [119]	22071	Male physicians	beta-carotene	50 mg q48	PO	Malignant neoplasm; composite endpoint (CV death, MI, and stroke)	12 y	CV events: beta-carotene 967, pl 972; CV death: beta-carotene 338, pl 313; MI: beta-carotene 468, pl 489
SUVIMAX [120]	13017	Adult subjects	Vit E/C, beta-carotene, selenium, and zinc	30 mg, 120 mg, 6 mg, 100 g, and 20 mg	PO	CV ischemic events	7.5 y	CV events: antiox 134, pl 137
HPS [121]	20536	CAD, PAD, DM, and HTN	Vit E/C, beta-carotene	600 mg, 250 mg, 20 mg	PO	Composite endpoint (CV death, and MI)	5 y	CV death: antiox 878, pl 840; MI: antiox 1063, pl 1047; CV events: antiox 2306, pl 2312
HOPE [122]	9541	CV disease or DM + additional CV RF	Vit E	400 IU	PO	Composite endpoint (CV death, MI, and stroke)	7 y	CV events: Vit E 1022, pl 985; CV death: Vit E 482, pl 475; MI: Vit E 724, pl 686
Mark et al. [123]	3318	Esophageal dysplasia	Vit E/C, beta-carotene	60 IU, 180 mg, and 15 mg	PO	CV death	6 y	CV death: antiox 22, pl 35
CARET [124]	1845	Exposure to asbestos or smoke	Vit E/A	15/30 mg, 25000 IU	PO	Lung cancer incidence	5.5 y	CV death: HR 1.26 (0.99–1.61)
WAVE [125]	213	Postmenopausal women with CAD	Vit E/C	400 IU, 500 mg	PO	Change in MLD	2.8 y	CV events: antiox 10, pl 5; CV death: antiox 4, pl 2; nonfatal MI: antiox 3, pl 1
HOPE [126]	9541	CV disease or DM + additional CV RF	Vit E	400 IU	PO	Composite endpoint (CV death, MI, stroke)	4.5 y	CV events: Vit E 772, pl 739; CV death: Vit E 342, pl 328; MI: Vit E 532, pl 524

CAD: coronary artery disease; CV: cardiovascular; d: days; DM: diabetes mellitus; HR: hazard ratio; HTN: arterial hypertension; m: months; MI: myocardial infarction; MLD: minimal luminal diameter; na: not available; PAD: peripheral artery disease, pl: placebo; PO: per os; pts: patients; RF: risk factor; vit: vitamin; y: years.