Effects of Homocysteine-Lowering With Folic Acid Plus Vitamin B12 vs Placebo on Mortality and Major Morbidity in Myocardial Infarction Survivors A Randomized Trial

被引:249
作者
Armitage, Jane M. [1 ]
Bowman, Louise [1 ]
Clarke, Robert J. [1 ]
Wallendszus, Karl [1 ]
Bulbulia, Richard [1 ]
Rahimi, Kazem [1 ]
Haynes, Richard [1 ]
Parish, Sarah [1 ]
Sleight, Peter [2 ]
Peto, Richard [1 ]
Collins, Rory [1 ]
机构
[1] Univ Oxford, Clin Trial Serv Unit, Oxford OX3 7LF, England
[2] Univ Oxford, Dept Cardiovasc Med, Oxford OX3 7LF, England
来源
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION | 2010年 / 303卷 / 24期
基金
英国医学研究理事会;
关键词
REQUIRING PROLONGED OBSERVATION; CARDIOVASCULAR EVENTS; RISK-FACTOR; PLASMA HOMOCYSTEINE; STROKE PREVENTION; VASCULAR-DISEASE; HIP FRACTURE; B-VITAMINS; SUPPLEMENTATION; FORTIFICATION;
D O I
10.1001/jama.2010.840
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Context Blood homocysteine levels are positively associated with cardiovascular disease, but it is uncertain whether the association is causal. Objective To assess the effects of reducing homocysteine levels with folic acid and vitamin B-12 on vascular and nonvascular outcomes. Design, Setting, and Patients Double-blind randomized controlled trial of 12 064 survivors of myocardial infarction in secondary care hospitals in the United Kingdom between 1998 and 2008. Interventions 2 mg folic acid plus 1 mg vitamin B12 daily vs matching placebo. Main Outcome Measures First major vascular event, defined as major coronary event (coronary death, myocardial infarction, or coronary revascularization), fatal or nonfatal stroke, or noncoronary revascularization. Results Allocation to the study vitamins reduced homocysteine by a mean of 3.8 mu mol/L (28%). During 6.7 years of follow-up, major vascular events occurred in 1537 of 6033 participants (25.5%) allocated folic acid plus vitamin B12 vs 1493 of 6031 participants (24.8%) allocated placebo (risk ratio [RR], 1.04; 95% confidence interval [CI], 0.97-1.12; P=.28). There were no apparent effects on major coronary events (vitamins, 1229 [20.4%], vs placebo, 1185 [19.6%]; RR, 1.05; 95% CI, 0.97-1.13), stroke (vitamins, 269 [4.5%], vs placebo, 265 [4.4%]; RR, 1.02; 95% CI, 0.86-1.21), or noncoronary revascularizations (vitamins, 178 [3.0%], vs placebo, 152 [2.5%]; RR, 1.18; 95% CI, 0.95-1.46). Nor were there significant differences in the numbers of deaths attributed to vascular causes (vitamins, 578 [9.6%], vs placebo, 559 [9.3%]) or nonvascular causes (vitamins, 405 [6.7%], vs placebo, 392 [6.5%]) or in the incidence of any cancer (vitamins, 678 [11.2%], vs placebo, 639 [10.6%]). Conclusion Substantial long-term reductions in blood homocysteine levels with folic acid and vitamin B12 supplementation did not have beneficial effects on vascular outcomes but were also not associated with adverse effects on cancer incidence.
引用
收藏
页码:2486 / 2494
页数:9
相关论文
共 48 条
[1]   Effect of folic acid and B vitamins on risk of cardiovascular events and total mortality among women at high risk for cardiovascular disease - A randomized trial [J].
Albert, Christine M. ;
Cook, Nancy R. ;
Gaziano, J. Michael ;
Zaharris, Elaine ;
MacFadyen, Jean ;
Danielson, Eleanor ;
Buring, Julie E. ;
Manson, JoAnn E. .
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2008, 299 (17) :2027-2036
[2]  
[Anonymous], 1991, Lancet, V338, P131, DOI 10.1016/0140-6736(91)90133-A
[3]  
BAKER F, 2002, CIRCULATION S2, V106, P2
[4]   Effect of folic acid supplementation on risk of cardiovascular diseases - A meta-analysis of randomized controlled trials [J].
Bazzano, Lydia A. ;
Reynolds, Kristi ;
Holder, Kevin N. ;
He, Jiang .
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2006, 296 (22) :2720-2726
[5]   Folic Acid Supplementation and Cardiovascular Disease: The State of the Art [J].
Bazzano, Lydia A. .
AMERICAN JOURNAL OF THE MEDICAL SCIENCES, 2009, 338 (01) :48-49
[6]   Homocysteine lowering and cardiovascular events after acute myocardial infarction [J].
Bonaa, KH ;
Njolstad, I ;
Ueland, PM ;
Schirmer, H ;
Tverdal, A ;
Steigen, T ;
Wang, H ;
Nordrehaug, JE ;
Arnesen, E ;
Rasmussen, K .
NEW ENGLAND JOURNAL OF MEDICINE, 2006, 354 (15) :1578-1588
[7]   A QUANTITATIVE ASSESSMENT OF PLASMA HOMOCYSTEINE AS A RISK FACTOR FOR VASCULAR-DISEASE - PROBABLE BENEFITS OF INCREASING FOLIC-ACID INTAKES [J].
BOUSHEY, CJ ;
BERESFORD, SAA ;
OMENN, GS ;
MOTULSKY, AG .
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 1995, 274 (13) :1049-1057
[8]   Homocysteine Lowering and Cognition in CKD: The Veterans Affairs Homocysteine Study [J].
Brady, Christopher B. ;
Gaziano, J. Michael ;
Cxypoliski, Roberta A. ;
Guarino, Peter D. ;
Kaufman, James S. ;
Warren, Stuart R. ;
Hartigan, Pamela ;
Goldfarb, David S. ;
Jamison, Rex L. .
AMERICAN JOURNAL OF KIDNEY DISEASES, 2009, 54 (03) :440-449
[9]  
Brattström L, 1998, BMJ-BRIT MED J, V316, P894, DOI 10.1136/bmj.316.7135.894
[10]   Folate, vitamin B12, and serum total homocysteine levels in confirmed Alzheimer disease [J].
Clarke, R ;
Smith, AD ;
Jobst, KA ;
Refsum, H ;
Sutton, L ;
Ueland, PM .
ARCHIVES OF NEUROLOGY, 1998, 55 (11) :1449-1455