Homocysteine lowering and cardiovascular events after acute myocardial infarction.
BACKGROUND
Homocysteine is a risk factor for cardiovascular disease. We evaluated the efficacy of homocysteine-lowering treatment with B vitamins for secondary prevention in patients who had had an acute myocardial infarction.


METHODS
The trial included 3749 men and women who had had an acute myocardial infarction within seven days before randomization. Patients were randomly assigned, in a two-by-two factorial design, to receive one of the following four daily treatments: 0.8 mg of folic acid, 0.4 mg of vitamin B12, and 40 mg of vitamin B6; 0.8 mg of folic acid and 0.4 mg of vitamin B12; 40 mg of vitamin B6; or placebo. The primary end point during a median follow-up of 40 months was a composite of recurrent myocardial infarction, stroke, and sudden death attributed to coronary artery disease.


RESULTS
The mean total homocysteine level was lowered by 27 percent among patients given folic acid plus vitamin B12, but such treatment had no significant effect on the primary end point (risk ratio, 1.08; 95 percent confidence interval, 0.93 to 1.25; P=0.31). Also, treatment with vitamin B6 was not associated with any significant benefit with regard to the primary end point (relative risk of the primary end point, 1.14; 95 percent confidence interval, 0.98 to 1.32; P=0.09). In the group given folic acid, vitamin B12, and vitamin B6, there was a trend toward an increased risk (relative risk, 1.22; 95 percent confidence interval, 1.00 to 1.50; P=0.05).


CONCLUSIONS
Treatment with B vitamins did not lower the risk of recurrent cardiovascular disease after acute myocardial infarction. A harmful effect from combined B vitamin treatment was suggested. Such treatment should therefore not be recommended. (ClinicalTrials.gov number, NCT00266487.).
Institute of Community Medicine, University of Tromsø, Tromsø, Norway. kaare.bonaa@stolav.no
Kaare Harald
KH
Bønaa
Inger
I
Njølstad
Per Magne
PM
Ueland
Henrik
H
Schirmer
Aage
A
Tverdal
Terje
T
Steigen
Harald
H
Wang
Jan Erik
JE
Nordrehaug
Egil
E
Arnesen
Knut
K
Rasmussen
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016757:Death, Sudden, Cardiac / Q000453:epidemiology / Q000517:prevention & control; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005492:Folic Acid / Q000097:blood / Q000627:therapeutic use*; D006801:Humans; D020138:Hyperhomocysteinemia / Q000150:complications / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000150:complications / Q000188:drug therapy* / Q000517:prevention & control; D016016:Proportional Hazards Models; D055502:Secondary Prevention; D020521:Stroke / Q000453:epidemiology; D014805:Vitamin B 12 / Q000097:blood / Q000627:therapeutic use*; D025101:Vitamin B 6 / Q000097:blood / Q000627:therapeutic use*
D025101:Vitamin B 6; D005492:Folic Acid; D014805:Vitamin B 12