Folate therapy and in-stent restenosis after coronary stenting.
BACKGROUND
Vitamin therapy to lower homocysteine levels has recently been recommended for the prevention of restenosis after coronary angioplasty. We tested the effect of a combination of folic acid, vitamin B6, and vitamin B12 (referred to as folate therapy) on the risk of angiographic restenosis after coronary-stent placement in a double-blind, multicenter trial.


METHODS
A total of 636 patients who had undergone successful coronary stenting were randomly assigned to receive 1 mg of folic acid, 5 mg of vitamin B6, and 1 mg of vitamin B12 intravenously, followed by daily oral doses of 1.2 mg of folic acid, 48 mg of vitamin B6, and 60 microg of vitamin B12 for six months, or to receive placebo. The angiographic end points (minimal luminal diameter, late loss, and restenosis rate) were assessed at six months by means of quantitative coronary angiography.


RESULTS
At follow-up, the mean (+/-SD) minimal luminal diameter was significantly smaller in the folate group than in the placebo group (1.59+/-0.62 mm vs. 1.74+/-0.64 mm, P=0.008), and the extent of late luminal loss was greater (0.90+/-0.55 mm vs. 0.76+/-0.58 mm, P=0.004). The restenosis rate was higher in the folate group than in the placebo group (34.5 percent vs. 26.5 percent, P=0.05), and a higher percentage of patients in the folate group required repeated target-vessel revascularization (15.8 percent vs. 10.6 percent, P=0.05). Folate therapy had adverse effects on the risk of restenosis in all subgroups except for women, patients with diabetes, and patients with markedly elevated homocysteine levels (15 micromol per liter or more) at baseline.


CONCLUSIONS
Contrary to previous findings, the administration of folate, vitamin B6, and vitamin B12 after coronary stenting may increase the risk of in-stent restenosis and the need for target-vessel revascularization.
Lange
Helmut
H
Kardiologische Praxis, Klinikum Links der Weser, Heart Center, Bremen, Germany.
Suryapranata
Harry
H
De Luca
Giuseppe
G
Börner
Caspar
C
Dille
Joep
J
Kallmayer
Klaus
K
Pasalary
M Noor
MN
Scherer
Eberhard
E
Dambrink
Jan-Henk E
JH
D000368:Aged; D017023:Coronary Angiography; D003327:Coronary Disease / Q000150:complications / Q000473:pathology / Q000628:therapy; D023903:Coronary Restenosis / Q000139:chemically induced / Q000517:prevention & control*; D003331:Coronary Vessels / Q000473:pathology; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005492:Folic Acid / Q000009:adverse effects* / Q000627:therapeutic use; D006710:Homocysteine / Q000097:blood; D006801:Humans; D020138:Hyperhomocysteinemia / Q000150:complications / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D015607:Stents; D017211:Treatment Failure; D014805:Vitamin B 12 / Q000009:adverse effects* / Q000627:therapeutic use; D025101:Vitamin B 6 / Q000009:adverse effects* / Q000627:therapeutic use
D006710:Homocysteine; D025101:Vitamin B 6; D005492:Folic Acid; D014805:Vitamin B 12