Decreased rate of coronary restenosis after lowering of plasma homocysteine levels

N Engl J Med. 2001 Nov 29;345(22):1593-600. doi: 10.1056/NEJMoa011364.

Abstract

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-tine 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.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angioplasty, Balloon, Coronary*
  • Coronary Angiography
  • Coronary Restenosis / prevention & control*
  • Coronary Stenosis / complications
  • Coronary Stenosis / pathology
  • Coronary Stenosis / therapy*
  • Coronary Vessels / pathology
  • Disease-Free Survival
  • Double-Blind Method
  • Drug Therapy, Combination
  • Female
  • Folic Acid / therapeutic use*
  • Homocysteine / blood
  • Humans
  • Hyperhomocysteinemia / complications
  • Hyperhomocysteinemia / drug therapy*
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Prospective Studies
  • Pyridoxine / therapeutic use*
  • Vitamin B 12 / therapeutic use*

Substances

  • Homocysteine
  • Folic Acid
  • Pyridoxine
  • Vitamin B 12