Clinical trials - TrialResults-center.org

pathology

Demonstrated benefit and harm

cardiovascular prevention

versus placebo or control

No demonstrated result for efficacy

folic acid, vit B12 and vit B6 inferior to control in terms of Non fatal MI in NORVIT (folic acid, B12 and vit B6) (Bonaa), 2006

folic acid, B12 inferior to placebo in terms of cardiovascular event (fatal and non fatal) in WENBIT (folic ac,B12), 2008

folic acid, vit B12 and vit B6 inferior to placebo 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	folic acid, B12 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	folic acid, B12 vs placebo			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	folic acid, vit B12 and vit B6 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	folic acid, vit B12 and vit B6 vs placebo			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	folic acid, vit B12 and vit B6 vs placebo	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]
CHAOS-2, 2002	folic acid vs placebo			Myocardial infarction 1.91 [0.96; 3.82]
FOLARDA (Liem), 2004	folic acid 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	folic acid 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	folic acid, B12 vs placebo		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	folic acid, vit B12 and vit B6 vs placebo	vascular death 0.86 [0.75; 0.99]		cardiovascular event 0.91 [0.82; 1.00]
CSPPT, 2015	folic acid vs placebo	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	folic acid, vit B12 and vit B6 vs placebo		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
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: