N Engl J Med 2001, 345(22):1593-1600
Schnyder,G.; Roffi,M.; Pin,R.; Flammer,Y.; Lange,H.; Eberli,F.R.; Meier,B.; Turi,Z.G.; Hess,O.M.
BACKGROUND: We have previously demonstrated an association between elevated total
plasma homocysteine levels and restenosis after percutaneous coronary angioplasty. We designed this study to
evaluate the effect of lowering plasma homocysteine levels on restenosis after coronary angioplasty.
METHODS: A combination of folic acid (1 mg), vitamin B12 (400 microg), and
pyridoxine (10 mg)--referred to as folate treatment--or placebo was administered to 205 patients (mean [+/-SD]
age, 61+/-11 years) for six months after successful coronary angioplasty in a prospective, double-blind,
randomized trial. The primary end point was restenosis within six months as assessed by quantitative coronary
angiography. The secondary end point was a composite of major adverse cardiac events.
RESULTS: Base-line characteristics and initial angiographic results after coronary
angioplasty were similar in the two study groups. Folate treatment significantly lowered plasma homocysteine
levels from 11.1+/-4.3 to 7.2+/-2.4 micromol per liter (P<0.001). At follow-up, the minimal luminal diameter
was significantly larger in the group assigned to folate treatment (1.72+/-0.76 vs. 1.45+/-0.88 mm, P=0.02),
and the degree of stenosis was less severe (39.9+/-20.3 vs. 48.2+/-28.3 percent, P=0.01). The rate of
restenosis was significantly lower in patients assigned to folate treatment (19.6 vs. 37.6 percent, P=0.01),
as was the need for revascularization of the target lesion (10.8 vs. 22.3 percent, P=0.047).
CONCLUSIONS: Treatment with a combination of folic acid, vitamin B12, and
pyridoxine significantly reduces homocysteine levels and decreases the rate of restenosis and the need for
revascularization of the target lesion after coronary angioplasty. This inexpensive treatment, which has
minimal side effects, should be considered as adjunctive therapy for patients undergoing coronary
angioplasty.