Table 4: Randomized controlled trials demonstrating no effect of antioxidant therapy.

SourceNumber of patientsInclusion criteriaAntioxidant agentDoseRouteEndpointsFollowupEvents

Virtamo et al. [111]27271Male smokersVit E, beta-carotene50 mg, 20 mgPOMajor coronary events (CV death, MI)6.1 yCV 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]1862Previous MIVit E, beta-carotene50 mg, 20 mgPOMajor coronary events (CV death, MI)5.3 yCV events: Vit E 94, beta-carotene 113, Vit E + beta-carotene 123, and pl 94

HATS [113]80CADVit E/C, beta-carotene, and selenium800 IU, 1 g, 25 mg, and 100 gPOComposite endpoint (CV death, MI, and PTCA/CABG)38 mCV events: antiox 9, pl 9; CV death: antiox 0, pl 1; nonfatal MI: antiox 1, pl 4

PHS II [114]14641Male physiciansVit E/C400 IU
500 mg
POComposite endpoint (CV death, MI, and stroke)8 yCV 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]8171High CV risk womenVit E/C, beta-carotene600 IU q48 h, 500 mg, and 50 mg q48 hPOComposite endpoint (CV death, MI, PTCA/CABG, and stroke)9.4 yCV 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]4495Subjects ≥ 1 RFVit E300 mgPOComposite endpoint (CV death, MI, and stroke)3.6 yCV events: Vit E 56, pl 53; CV death: Vit E 22, pl 26; MI: Vit E 22, pl 25

GISSI-prevenzione [117]5660Recent MIVit E300 mgPOComposite endpoint (CV death, MI, and stroke)3.5 yCV events: Vit E 371, pl 414; CV death: Vit E 155, pl 193; MI: Vit E 22, pl 25

Greenberg et al. [118]1720Skin cancerbeta-carotene50 mgPOCV death4.3 yCV death: beta-carotene 68, pl 59

PHS [119]22071Male physiciansbeta-carotene50 mg q48POMalignant neoplasm; composite endpoint (CV death, MI, and stroke)12 yCV events: beta-carotene 967, pl 972; CV death: beta-carotene 338, pl 313; MI: beta-carotene 468, pl 489

SUVIMAX [120]13017Adult subjectsVit E/C, beta-carotene, selenium, and zinc30 mg, 120 mg, 6 mg, 100 g, and 20 mgPOCV ischemic events7.5 yCV events: antiox 134, pl 137

HPS [121]20536CAD, PAD, DM, and HTNVit E/C, beta-carotene600 mg, 250 mg, 20 mgPOComposite endpoint (CV death, and MI)5 yCV death: antiox 878, pl 840; MI: antiox 1063, pl 1047; CV events: antiox 2306, pl 2312

HOPE [122]9541CV disease or DM + additional CV RFVit E400 IUPOComposite endpoint (CV death, MI, and stroke)7 yCV events: Vit E 1022, pl 985; CV death: Vit E 482, pl 475; MI: Vit E 724, pl 686

Mark et al. [123]3318Esophageal dysplasiaVit E/C, beta-carotene60 IU, 180 mg, and 15 mgPOCV death6 yCV death: antiox 22, pl 35

CARET [124]1845Exposure to asbestos or smokeVit E/A15/30 mg, 25000 IUPOLung cancer incidence5.5 yCV death: HR 1.26 (0.99–1.61)

WAVE [125]213Postmenopausal women with CADVit E/C400 IU, 500 mgPOChange in MLD2.8 yCV events: antiox 10, pl 5; CV death: antiox 4, pl 2; nonfatal MI: antiox 3, pl 1

HOPE [126]9541CV disease or DM + additional CV RFVit E400 IUPOComposite endpoint (CV death, MI, stroke)4.5 yCV 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.