Q&A

Should patients with coronary disease and high homocysteine take folic acid?

J Fam Pract. 2003 January;52(1):12-31
By
John J. O’Connor, MD
Linda N. Meurer, MD, MPH
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  • BACKGROUND: Should patients with coronary artery disease and high homocysteine levels take folic acid? Plasma homocysteine levels predict outcome after coronary angioplasty, and lowering plasma homocysteine levels significantly decreases restenosis after coronary angioplasty.
  • STUDY POPULATION: The investigators enrolled 553 participants who had successfully undergone angioplasty for at least one significant coronary stenosis (≥50%). Subjects in the treatment and control groups were predominantly male (79% and 82%), and had mean ages of 62 and 63 years. Patients were excluded if they had unstable angina, subacute myocardial infarction (within the previous 2 weeks), renal insufficiency (serum creatinine >1.8 mg/dL), or were taking vitamins.
  • STUDY DESIGN AND VALIDITY: The study was a randomized, double-blind, placebo-controlled trial. After successful angioplasty, defined as residual diameter stenosis less than 35% with normal flow pattern (TIMI III criteria), patients were randomly assigned to receive a supplement containing folic acid (1 mg), vitamin B12 (400 μg), and vitamin B6 (10 mg) or placebo daily for 6 months. Treatment was discontinued after 6 months and the participants were then followed for another 6 months. Fasting total plasma homocysteine levels were measured on admission and at 6 months.
  • OUTCOMES MEASURED: The main outcomes evaluated were death, cardiac death (defined as sudden, unexpected death or death related to myocardial infarction), nonfatal myocardial infarction (new Q-wave in 2 or more electrocardiogram leads), the need for repeat revascularization for proven ischemia demonstrated by either follow-up cardiac events or a positive noninvasive stress test with significant angiographic stenosis of at least 50%, or a composite of these outcomes.
  • RESULTS: The composite outcomes of death, cardiac death, recurrence, or need for revascularization was significantly decreased with the vitamin therapy (hazard ratio, 0.68; 95% confidence interval [CI], 0.48–0.96). For the 6 months after the angioplasty, one outcome would have been avoided for every 13 patients treated. Individually, only the need for repeat revascularization was significantly affected by therapy (hazard ratio, 0.62; 95% CI, 0.40–0.97). Adjustment for multiple risk factors including age, sex, and variables known to influence the need for target lesion revascularization after coronary angioplasty (use of stents, treatment of restenotic lesions, vessel size, post procedural minimal luminal diameter, target lesion location, and use of glycoprotein IIb/IIIa inhibitors) did not significantly change the relationship between homocysteine-lowering therapy and the need for repeat target lesion revascularization.
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PRACTICE RECOMMENDATIONS

All patients with known coronary artery disease should take prescription strength (1 mg/d) folic acid, vitamin B12 (400 μg/d), and vitamin B6 (10 mg/d), which have few if any known adverse effects. In this study, therapy to reduce homocysteine levels with prescription strength folic acid (1 mg) and vitamins B12 and B6 for 6 months following coronary angioplasty reduced the risk of need for revascularization of target lesions and of overall adverse cardiac events at least 6 months following cessation of therapy.

Based on this study, it is unknown whether the benefit is related to baseline homocysteine levels or whether there is further benefit to continuing treatment beyond 6 months. Over-the-counter folic acid supplements (800 μg or less) were not studied and may not be as beneficial.

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Revascularization not superior to conservative treatment of acute coronary syndromes