Don't End It With WENBIT -- Details Needed on B Vitamins, Stroke, and Cancer
From Heartwire — a professional news service of WebMD
August 20, 2008 — The Western Norway B-Vitamin Intervention Trial (WENBIT), showing no benefit of either folate with vitamin B12 or vitamin B6 in patients with established heart disease, is now published in the August 20, 2008, issue of the Journal of the American Medical Association [1]. First presented at the European Society of Cardiology Congress 2007 by Dr Marta Ebbing (Haukeland University Hospital, Bergen, Norway), as reported by heartwire, the trial is the latest in a series of studies suggesting that B-vitamin supplementation is not justified as secondary prevention in heart disease and that its intended target, homocysteine, is a marker of coronary heart disease (CHD), rather than a "modifiable cause" of heart disease.
Commenting on the published study to heartwire, Ebbing pointed out that the rigorous design of the WENBIT study makes the results an important addition to the field. Patients underwent coronary angiography before entering the study, were not already taking B vitamins, and Norway, unlike many other countries, does not have folic-acid fortification of foods.
"WENBIT confirms and adds further evidence to results from previously published and similar homocysteine-lowering B-vitamin trials in populations with established or at increased risk of cardiovascular disease," she said.
WENBIT results
In WENBIT, 3096 CHD patients were randomized in a 2 x 2 factorial design to one of four groups to receive a daily oral dose of folic acid (0.8 mg) plus vitamin B12 (0.4 mg) and vitamin B6 (40 mg); folic acid with vitamin B12 alone; vitamin B6 alone; or placebo. Homocysteine levels declined by about 30% in the folic-acid/B12 group at one year; the trial, however, was terminated early after results from the Norwegian Vitamin (NORVIT) trial suggested a possible increase in cancer risk with B-vitamin supplementation. After a median follow-up of 38 months, there was no significant difference in the risk of death or major cardiovascular events among the four groups.
But like the NORVIT trial before it, WENBIT hinted at a possible cancer risk — a worrying trend, given that several Western countries have or are considering mandatory folic-acid fortification of staple foods, including cereals, spreads, and flour, to prevent neural-tube defects in babies.
"Both in NORVIT and in WENBIT there was a numerically larger incidence of cancer in the groups treated with folic acid and vitamin B12, and although this could be due to chance, the possible harmful effects of folic-acid treatment/supplementation on cancer development should be explored," Ebbing told heartwire. Researchers in NORVIT and WENBIT are currently working to provide combined results from an extended follow-up of the almost 7000 patients who participated in these trials to explore such possible harmful short- and long-term effects from the intervention.
Furthermore, she said, the B-Vitamin Trialists Treatment Collaboration is planning to collaborate on a meta-analysis of results from completed and ongoing B-vitamin intervention trials. "Incident cancers will be one of the clinical end points in this analysis," she said.
There is also some suggestion that the incidence of stroke is actually reduced by folic acid/vitamin B12, and this potential effect may also warrant further scrutiny, the WENBIT investigators note.
WENBIT: Percentage of patients with cardiovascular events
End point
Folic acid+B12+B6
Folic acid+B12
B6
Placebo
Primary end point
12.2
16.3
13.7
12.5
All-cause death
4.5
4.9
3.6
3.9
Acute MI
7.7
9.9
7.1
7.4
Unstable angina
2.9
3.8
3.1
3.5
Nonfatal thromboembolic stroke
1.4
2.2
2.6
2.4
Cancer
6.0
5.1
4.9
4.0
Dr Salim Yusuf (McMaster University, Hamilton, ON), who discussed the trial when it was first presented last year, pointed out that results from the VITAmins TO Prevent Stroke (VITATOPS) trial (8000 stroke patients) and the SEARCH trial in 12,000 heart-disease patients will more than double the total database on homocysteine lowering. Echoing Ebbing et al's conclusions, Yusuf stated: "There is no reason now to lower homocysteine levels, but it is still too early to write off the hypothesis completely."
This trial was funded by the Advanced Research Program and Research Council of Norway, the Norwegian Foundation for Health and Rehabilitation, the Norwegian Heart and Lung Patient Organisation, the Norwegian Ministry of Health and Care Services, the Western Norway Regional Health Authority, the Department of Heart Disease at Haukeland University Hospital, Locus for Homocysteine and Related Vitamins at the University of Bergen, Locus for Cardiac Research at the University of Bergen, the Foundation to Promote Research Into Functional Vitamin B12 Deficiency, Bergen, Norway, and Alpharma Inc, Copenhagen, Denmark.
One study author has disclosed that he is a member of the steering board of the nonprofit Foundation to Promote Research Into Functional Vitamin B12 Deficiency. Two study authors have received consulting fees from Nycomed. The remaining study authors have disclosed no relevant financial relationships.
Source
Ebbing M, Bleie Ø, Ueland PM, et al. Mortality and cardiovascular events in patients treated with homocysteine-lowering B vitamins after coronary angiography. A randomized controlled trial. JAMA. 2008;300:795-804
From Heartwire — a professional news service of WebMD
August 20, 2008 — The Western Norway B-Vitamin Intervention Trial (WENBIT), showing no benefit of either folate with vitamin B12 or vitamin B6 in patients with established heart disease, is now published in the August 20, 2008, issue of the Journal of the American Medical Association [1]. First presented at the European Society of Cardiology Congress 2007 by Dr Marta Ebbing (Haukeland University Hospital, Bergen, Norway), as reported by heartwire, the trial is the latest in a series of studies suggesting that B-vitamin supplementation is not justified as secondary prevention in heart disease and that its intended target, homocysteine, is a marker of coronary heart disease (CHD), rather than a "modifiable cause" of heart disease.
Commenting on the published study to heartwire, Ebbing pointed out that the rigorous design of the WENBIT study makes the results an important addition to the field. Patients underwent coronary angiography before entering the study, were not already taking B vitamins, and Norway, unlike many other countries, does not have folic-acid fortification of foods.
"WENBIT confirms and adds further evidence to results from previously published and similar homocysteine-lowering B-vitamin trials in populations with established or at increased risk of cardiovascular disease," she said.
WENBIT results
In WENBIT, 3096 CHD patients were randomized in a 2 x 2 factorial design to one of four groups to receive a daily oral dose of folic acid (0.8 mg) plus vitamin B12 (0.4 mg) and vitamin B6 (40 mg); folic acid with vitamin B12 alone; vitamin B6 alone; or placebo. Homocysteine levels declined by about 30% in the folic-acid/B12 group at one year; the trial, however, was terminated early after results from the Norwegian Vitamin (NORVIT) trial suggested a possible increase in cancer risk with B-vitamin supplementation. After a median follow-up of 38 months, there was no significant difference in the risk of death or major cardiovascular events among the four groups.
But like the NORVIT trial before it, WENBIT hinted at a possible cancer risk — a worrying trend, given that several Western countries have or are considering mandatory folic-acid fortification of staple foods, including cereals, spreads, and flour, to prevent neural-tube defects in babies.
"Both in NORVIT and in WENBIT there was a numerically larger incidence of cancer in the groups treated with folic acid and vitamin B12, and although this could be due to chance, the possible harmful effects of folic-acid treatment/supplementation on cancer development should be explored," Ebbing told heartwire. Researchers in NORVIT and WENBIT are currently working to provide combined results from an extended follow-up of the almost 7000 patients who participated in these trials to explore such possible harmful short- and long-term effects from the intervention.
Furthermore, she said, the B-Vitamin Trialists Treatment Collaboration is planning to collaborate on a meta-analysis of results from completed and ongoing B-vitamin intervention trials. "Incident cancers will be one of the clinical end points in this analysis," she said.
There is also some suggestion that the incidence of stroke is actually reduced by folic acid/vitamin B12, and this potential effect may also warrant further scrutiny, the WENBIT investigators note.
WENBIT: Percentage of patients with cardiovascular events
End point
Folic acid+B12+B6
Folic acid+B12
B6
Placebo
Primary end point
12.2
16.3
13.7
12.5
All-cause death
4.5
4.9
3.6
3.9
Acute MI
7.7
9.9
7.1
7.4
Unstable angina
2.9
3.8
3.1
3.5
Nonfatal thromboembolic stroke
1.4
2.2
2.6
2.4
Cancer
6.0
5.1
4.9
4.0
Dr Salim Yusuf (McMaster University, Hamilton, ON), who discussed the trial when it was first presented last year, pointed out that results from the VITAmins TO Prevent Stroke (VITATOPS) trial (8000 stroke patients) and the SEARCH trial in 12,000 heart-disease patients will more than double the total database on homocysteine lowering. Echoing Ebbing et al's conclusions, Yusuf stated: "There is no reason now to lower homocysteine levels, but it is still too early to write off the hypothesis completely."
This trial was funded by the Advanced Research Program and Research Council of Norway, the Norwegian Foundation for Health and Rehabilitation, the Norwegian Heart and Lung Patient Organisation, the Norwegian Ministry of Health and Care Services, the Western Norway Regional Health Authority, the Department of Heart Disease at Haukeland University Hospital, Locus for Homocysteine and Related Vitamins at the University of Bergen, Locus for Cardiac Research at the University of Bergen, the Foundation to Promote Research Into Functional Vitamin B12 Deficiency, Bergen, Norway, and Alpharma Inc, Copenhagen, Denmark.
One study author has disclosed that he is a member of the steering board of the nonprofit Foundation to Promote Research Into Functional Vitamin B12 Deficiency. Two study authors have received consulting fees from Nycomed. The remaining study authors have disclosed no relevant financial relationships.
Source
Ebbing M, Bleie Ø, Ueland PM, et al. Mortality and cardiovascular events in patients treated with homocysteine-lowering B vitamins after coronary angiography. A randomized controlled trial. JAMA. 2008;300:795-804
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