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Homocysteine lowering after percutaneous coronary intervention


The influence of homocysteine levels in blood on heart disease was visited in Bandolier 57 . The evidence that lowering homocysteine levels by increasing folic acid and B vitamin intake is still a matter of debate, at least for those of us not known to have very high homocysteine levels.

But what of secondary prevention? Is there any benefit of lowering homocysteine levels in people with high cardiovascular risk, like after heart surgery? No answers yet on that either, but a randomised trial tells us that folate and B vitamins improve outcomes after percutaneous interventions [1].


Patients undergoing percutaneous angioplasty of at least one significant coronary stenosis greater than 50% were randomised to receive folic acid (1 mg/day), vitamin B12 (400 μg/day) and vitamin B6 (10 mg/day) or placebo for six months. Not included were patients with unstable angina, subacute myocardial infarction, renal insufficiency or patients taking vitamin supplements. Follow up was performed at six months and one year. Adverse clinical events were:


There were 272 patients given folate and vitamins and 281 given placebo. They were well matched at baseline, but at six months those in the folate plus vitamin group had mean plasma homocysteine levels that were 26% lower (at 1.0 mg/L; 7.5 μmol/L) than in those given placebo.

All the adverse clinical events occurred less frequently with folate and vitamins than with placebo (Figure 1). This was statistically significant for target vessel and any revascularisation, and for any event. An adverse clinical event occurred in 15% of patients with folate and vitamins, compared with 23% with placebo. The adjusted relative risk was 0.7 (0.47 to 0.94), and the NNT was 14 (7 to 122).

Figure 1: Effects of placebo and vitamin supplementation to reduce blood homocysteine on adverse clinical outcomes after percutaneous coronary interventions

For every 14 patients undergoing percutaneous cardiac interventions and treated with folate and vitamins for six months, one fewer will experience an adverse clinical event at one year than if they had been treated with placebo.

The only adverse events were two patients taking vitamins and folate who discontinued because of pruritus.


This is a lovely trial from Switzerland that takes epidemiology into the clinic, and adds to the store of positive messages about the use of folate. As many as five other acronymed studies are presently underway in heart disease and stroke, so evidence will build as these trials report over the next few years.

The exact place of B vitamin and folate supplements in people with cardiovascular disease still needs to be defined. There seems to be little downside, with few and mild adverse events reported here.

For those of us who want to join the bandwagon, though, the message still remains that eating fruit and vegetables is not enough. You'd need several plates of broccoli to even approach the 400 μg a day that seems to be needed. A multi-vitamin with at least 200 μg is easier.


  1. G Schnyder et al. Effect of homocysteine-lowering therapy with folic acid, vitamin B12, and vitamin B6 on clinical outcome after percutaneous coronary intervention. JAMA 2002 288: 973-979.
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