Folate worsens outcomes after placement of coronary stent

Journal of Family Practice, Oct, 2004 by H. Lange, H Suryapranata, G. DeLuca

Lange H, Suryapranata H, DeLuca G, et al. Folate therapy and in-stent restenosis after coronary stenting. N Engl J Med 2004; 350:2673-2681.

* CLINICAL QUESTION

Does B-vitamin supplementation reduce the risk of restenosis after coronary stenting?

* BOTTOM LINE

Intensive folate therapy seems to increase the risk of restenosis after coronary stent placement, particularly in men, those without diabetes, and those with normal homocysteine levels. (LOE=1b)

* STUDY DESIGN

Randomized controlled trial (double-blinded)

* ALLOCATION

Uncertain

* SETTING

Inpatient (any location) with outpatient follow-up

* SYNOPSIS

Homocysteine is a risk factor for heart disease, so anything that modifies homocysteine levels among high-risk patients must be helpful, right? Not necessarily. These German and Dutch researchers randomized patients following placement of a coronary stent to receive folate therapy (n=316) or matching placebo (n=320). Folate therapy consisted of intravenous boluses of 1 mg folic acid, 5 mg vitamin B6, and 1 mg vitamin B12, followed daily oral doses of 1.2 mg folic acid, 48 mg vitamin B6, and 60 [micro]g vitamin B12.

Patients with recent myocardial infarction, renal dysfunction, left main disease, or in-stent restenosis were excluded, as were those already taking vitamins. Groups were balanced at the start of the study, analysis was by intention to treat, but allocation concealment was not described.

At the end of the 8-month study period, major adverse coronary events were more likely in the folate group (16.8% vs 10.9%; P=.03; number needed to treat=17), primarily related to an increase in the need for target vessel revascularization. Subgroup analysis found that the risk of restenosis was especially noteworthy in men, patients without diabetes, and patients with a baseline homocysteine level lower than 15 [micro]mol/L. However, the converse was not true: women, patients with diabetes, and those with elevated homocysteine levels did not see any significant benefit from folate therapy.