| cardiovascular prevention | All results are NS for efficacy inferior to control in terms of Non fatal MI in NORVIT (folic acid, B12 and vit B6) (Bonaa), 2006 inferior to control in terms of cardiovascular event (fatal and non fatal) in WENBIT (folic ac,B12), 2008 inferior to control in terms of Death from any cause in SU.FOL.OM3 | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| NORVIT (folic acid + B12) (Bonaa), 2006 | vs control | | | Death from any cause 1.02 [0.84; 1.24] Non fatal MI 1.13 [0.95; 1.34] Incident cancer 1.22 [0.88; 1.68] stroke (fatal & non fatal) 1.00 [0.68; 1.48] Death from CHD 0.96 [0.75; 1.23] cardiovascular event (fatal and non fatal) 1.07 [0.93; 1.22] | | SEARCH, 2007 | vs control | | | Death from any cause 1.03 [0.95; 1.12] Death from cardiovascular causes 1.04 [0.93; 1.17] Myocardial infarction 1.05 [0.97; 1.13] Non fatal MI 1.00 [0.88; 1.14] Incident cancer 1.07 [0.96; 1.19] stroke (fatal & non fatal) 1.02 [0.86; 1.21] Death from CHD 1.09 [0.96; 1.24] cardiovascular event (fatal and non fatal) 1.03 [0.97; 1.09] | | NORVIT (folic acid, B12 and vit B6) (Bonaa), 2006 | vs control | | Non fatal MI 1.28 [1.00; 1.62] | Death from any cause 1.18 [0.90; 1.54] Myocardial infarction 1.20 [0.99; 1.45] Incident cancer 1.01 [0.66; 1.55] stroke (fatal & non fatal) 0.78 [0.45; 1.37] Death from CHD 1.16 [0.83; 1.62] cardiovascular event (fatal and non fatal) 1.18 [0.98; 1.41] | | WAFACS, 2008 | vs control | | | Death from any cause 0.98 [0.83; 1.15] Death from cardiovascular causes 1.02 [0.77; 1.35] Myocardial infarction 0.88 [0.63; 1.22] stroke (fatal & non fatal) 1.14 [0.83; 1.57] Death from CHD 1.01 [0.86; 1.18] cardiovascular event (fatal and non fatal) 1.04 [0.92; 1.18] | | HOPE-2 (Lonn), 2006 | vs control | stroke (fatal & non fatal) 0.76 [0.59; 0.96] | | Death from any cause 0.99 [0.88; 1.11] Death from cardiovascular causes 0.95 [0.81; 1.11] Death due to cancer 0.99 [0.75; 1.31] Myocardial infarction 0.98 [0.85; 1.13] Incident cancer 1.06 [0.92; 1.21] cardiovascular event (fatal and non fatal) 0.95 [0.85; 1.06] | | VISP (Toole), 2004 | vs control | | | Death from any cause 0.86 [0.66; 1.11] Myocardial infarction 0.90 [0.66; 1.23] stroke (fatal & non fatal) 1.04 [0.84; 1.29] cardiovascular event (fatal and non fatal) 0.97 [0.84; 1.12] | | CHAOS-2, 2002 | vs control | | | Myocardial infarction 1.91 [0.96; 3.82] | | FOLARDA (Liem), 2004 | vs control | | | Death from any cause 0.88 [0.30; 2.54] Myocardial infarction 0.82 [0.33; 2.01] stroke (fatal & non fatal) ∞ [NaN; ∞] | | GOES (Liem), 2003 | vs control | | | Death from any cause 0.84 [0.39; 1.78] Death from cardiovascular causes 0.76 [0.29; 2.01] Myocardial infarction 0.73 [0.17; 3.24] Non fatal MI 0.73 [0.17; 3.24] stroke (fatal & non fatal) 1.30 [0.29; 5.77] cardiovascular event (fatal and non fatal) 1.10 [0.70; 1.70] | | WENBIT (folic ac,B12), 2008 | vs control | | cardiovascular event (fatal and non fatal) 1.30 [1.02; 1.66] | Death from any cause 1.28 [0.80; 2.04] Myocardial infarction 1.32 [0.95; 1.84] Incident cancer 1.27 [0.80; 2.02] stroke (fatal & non fatal) 0.90 [0.47; 1.73] | | VITATOPS, 2010 | vs control | vascular death 0.86 [0.75; 0.99] | | cardiovascular event 0.91 [0.82; 1.00] | | CSPPT, 2015 | vs control | stroke (fatal & non fatal) 0.79 [0.68; 0.93] cardiovascular event (fatal and non fatal) 0.80 [0.69; 0.92] | | Death from any cause 0.94 [0.81; 1.10] Death from cardiovascular causes 1.00 [0.66; 1.53] Myocardial infarction 1.04 [0.60; 1.82] | | SU.FOL.OM3 | vs control | | Death from any cause 1.62 [1.13; 2.33] | Myocardial infarction 0.90 [0.62; 1.32] Non fatal MI 0.89 [0.54; 1.46] stroke (fatal & non fatal) 0.59 [0.35; 1.01] cardiovascular event (fatal and non fatal) 0.93 [0.68; 1.26] |
| Trial | Treatments | Patients | Method |
|---|
| NORVIT (folic acid + B12) (Bonaa), 2006 | folic acid 0.8mg and B12 0.4 mg daily
(n=1872) vs. no folic acid and B12
(n=1877) patients received also Vit B6 or placebo in a two by two factorial design
| men and women who had had an acute myocardial infarction within seven days before
| double-blind Factorial plan Sample size: 1872/1877 Primary endpoint: CV events (fatal and non ftala MI, stroke, sudden death) FU duration: 36 months
| | SEARCH, 2007 | folic acid 2mg/d + vitamin B12 1mg/d (n=6033) vs. placebo (n=6031) factorial design of homocysteine-lowering
therapy and simvastatin (80mg/d vs 20mg/d) | patients survivors of myocardial infarction | double blind Factorial plan Sample size: 6033/6031 Primary endpoint: major cardiovascular events FU duration: 7 years | | NORVIT (folic acid, B12 and vit B6) (Bonaa), 2006 | 0.8 mg of folic acid, 0.4 mg of vitamin B12, and 40 mg of vitamin B6 (n=937) vs. placebo (n=943) factorial design of folic acid plus B12 and B6 | men and women who had had an acute myocardial infarction within seven days | double-blind Factorial plan Sample size: 937/943 Primary endpoint: CV events(fatal and non ftala MI, stroke, sudden death) FU duration: 36 months | | WAFACS, 2008 | folic acid 2.5mg, vitamin B6 50mg, and vitamin B12 1mg daily (n=2721) vs. placebo (n=2721) | women aged 42 years or older, with either a history of CVD or 3 or more coronary risk factors | double blind Parallel groups Sample size: 2721/2721 Primary endpoint: cardiovascular events FU duration: 7.3 y | | HOPE-2 (Lonn), 2006 | folic acid, 2.5 mg, vitamin B6,50 mg and vitamin B12, 1mg (n=2758) vs. placebo (n=2764) | patients 55 years of age or older who had vascular disease
or diabetes and
additional risk factors for atherosclerosis | double blind Parallel groups Sample size: 2758/2764 Primary endpoint: cardiovascular events FU duration: Jan 2000 - dec 2000 | | VISP (Toole), 2004 | high-dose of folic acid, pyridoxine (vitamin B6),
and cobalamin (vitamin B12) (n=1827) vs. low-dose of folic acid, pyridoxine (vitamin B6),
and cobalamin (vitamin B12) (n=1853) | adults with nondisabling cerebral infarction | double blind Parallel groups Sample size: 1827/1853 Primary endpoint: Recurrent cerebral infarction FU duration: 2 y | | CHAOS-2, 2002 | folic acid 5 mg per day (for 2 years) (n=942) vs. placebo (n=940) | patient with CHD | double blind Parallel groups Sample size: 942/940 Primary endpoint: CV death, MI, revascularization FU duration: 1.7 y | | FOLARDA (Liem), 2004 | folic acid 5 mg per day for 1 year (n=140) vs. usual care (n=143) | patients with acute MI and total cholesterol >6.5 mmol/l | open Parallel groups Sample size: 140/143 Primary endpoint: not defined FU duration: 1 year pilot trial | | GOES (Liem), 2003 | folic acid 0.5 mg per day (n=300) vs. usual care (n=293) | patients with stable coronary artery disease | open Parallel groups Sample size: 300/293 Primary endpoint: CV events FU duration: 24 months | | WENBIT (folic ac,B12), 2008 | folic acid 0.8mg, vit B12 0.4mg daily
(n=772) vs. placebo
(n=780) 4 arms: folic acid+B12+B6, folic ac+B12, B6, placebo (2x2 factorial design B6 vs PBO, folic ac+B12 vs pbo)
| adult participants undergoing coronary angiography
| double blind Factorial plan Sample size: 772/780 Primary endpoint: all death, MI, unstable angina, stroke FU duration: 38.4 mo
| | VITATOPS, 2010 | folic acid and vitamins B12 and B6 in a single tablet (n=4089) vs. placebo (n=4075) | patients with recent stroke or TIA (within the past seven months) | double-blind Parallel groups Sample size: 4089/4075 Primary endpoint: nonfatal stroke, nonfatal MI, vascular death FU duration: 3.4 y | | CSPPT, 2015 | enalapril 10 mg / folic acid 0.8 mg daily (n=10348) vs. Enalapril maleate 10 mg daily (n=10354) | patients with primary hypertension | double-blind Parallel groups Sample size: 10348/10354 Primary endpoint: symptomatic stroke ( ischemic or hemorrhagic) FU duration: | | SU.FOL.OM3 | supplementation with natural foLate, vitamin B6 and B12 (n=1242) vs. placebo (n=1259) factorial design with as 2nd comparison omega 3 fatty acids (600 mg of eicosapentanoic acid and
docosahexaenoic acid at a ratio of 2:1) versus placebo | patients with coronary or cerebral event within the previous 12 months | double-blind Parallel groups Sample size: 1242/1259 Primary endpoint: MI, stroke, CV death FU duration: |
|
| post stroke | All results are NS for efficacy | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| VISP (Toole), 2004 | vs low dose - folic acid, vit B12 and vit B6 | | | Death from any cause 0.86 [0.66; 1.11] Myocardial infarction 0.90 [0.66; 1.23] stroke (fatal & non fatal) 1.04 [0.84; 1.29] cardiovascular event (fatal and non fatal) 0.97 [0.84; 1.12] | | VITATOPS, 2010 | vs low dose - folic acid, vit B12 and vit B6 | vascular death 0.86 [0.75; 0.99] | | cardiovascular event 0.91 [0.82; 1.00] |
| Trial | Treatments | Patients | Method |
|---|
| VISP (Toole), 2004 | high-dose of folic acid, pyridoxine (vitamin B6),
and cobalamin (vitamin B12) (n=1827) vs. low-dose of folic acid, pyridoxine (vitamin B6),
and cobalamin (vitamin B12) (n=1853) | adults with nondisabling cerebral infarction | double blind Parallel groups Sample size: 1827/1853 Primary endpoint: Recurrent cerebral infarction FU duration: 2 y | | VITATOPS, 2010 | folic acid and vitamins B12 and B6 in a single tablet (n=4089) vs. placebo (n=4075) | patients with recent stroke or TIA (within the past seven months) | double-blind Parallel groups Sample size: 4089/4075 Primary endpoint: nonfatal stroke, nonfatal MI, vascular death FU duration: 3.4 y |
|
