Some evidence links hyperhomocystinemia and coronary artery disease. Folate supplementation decreases homocysteine levels, but clinical trials of supplementation to prevent restenosis after angioplasty have produced conflicting results. Lange and colleagues conducted a trial of folate supplementation after angioplasty and coronary stent placement.
This randomized, double-blind, placebo-controlled study enlisted 636 patients who had recently had successful coronary artery stents placement. Post-procedure, participants were randomized to placebo or folate therapy (intravenous bolus followed by oral maintenance therapy with 1.2 mg of folic acid, 48 mg of vitamin B6, and 60 mcg of vitamin B12). Homocysteine levels and a repeat coronary angiogram were checked after six months of treatment. Revascularization procedures were performed if needed on the originally stented vessel, according to predetermined clinical criteria.
Clopidogrel therapy was used for four weeks after stenting in all subjects, and daily aspirin use continued throughout the study period. Approximately 40 percent of subjects in both groups were taking a statin medication during the trial. Of the 636 originally enrolled patients, 14 percent did not complete the six months of supplementation, and a further 10 percent declined to have follow-up angiography.
Homocysteine levels declined significantly in those randomized to folate therapy (from a baseline average of 12.2 μmol per L to 9.0 μmol per L at six months). Repeat angiography at six months showed a smaller coronary artery diameter in the stented target vessel among those receiving active medication, compared with placebo recipients. A nonsignificant trend toward a greater need for target-vessel revascularization was noted in those taking folate supplements. No significant difference in rates of death or myocardial infarction was noted in the two treatment arms of the study.
Subgroup analysis showed that patients with diabetes and those with higher baseline homocysteine levels had a somewhat lowered risk of restenosis with folate therapy. An accompanying editiorial notes that the previously heralded benefit of folate supplementation that was reported in the Swiss Heart Study was restricted largely to those who had balloon angioplasty without stent placement, a practice that is no longer common.
The authors conclude that folate therapy after coronary stenting is not helpful in reducing restenosis and may be harmful.