June 23, 2004 -- A folate and vitamin B-based therapy that lowers homocysteine levels may actually cause more harm than good. Contradicting previous findings and popular opinion, a new study indicates that folate and other B vitamins may actually increase the risk of artery narrowing following angioplasty.
Three B vitamins -- including folate -- have been considered an insurance policy to prevent renarrowing after surgery. That's because the nutrients work together to help lower levels of homocysteine, which has been linked to a higher risk of heart disease, such as the buildup of plaque in arteries of the heart.
The American Heart Association has not stated that high homocysteine level is a major risk factor for heart disease, unlike major risks such as high cholesterol or diabetes.
In a well-publicized study the three-vitamin regimen lowered the risk of renarrowing after angioplasty by almost 40%.
New Study, Opposite Results
But now, European researchers find an opposite effect and report that patients who took folate, B-6, and B-12 following stented angioplasty actually had a higher risk of renarrowing than those getting placebo drugs. After studying 636 patients, they report in this week's New England Journal of Medicine that:
- 35% of those put on vitamin supplements for 6 months experienced outright stent failure, compared with only 27% who took placebo pills.
- 16% of vitamin-treated patients needed subsequent procedures to reopen arteries, compared with 11% of those getting the phony drugs.
- The arterial openings in vitamin-taking patients shrunk more, to an average of 1.59 millimeters compared with 1.74 millimeters in the placebo group.
While the differences were slight, does this mean that B vitamin therapy shouldn't be recommended following angioplasty, as suggested by study researcher Helmut Lange, MD, and his colleagues?
Not necessarily, say two experts contacted by WebMD.
Reading Between the Results
"I have been using folate therapy for many years, and will continue to do so -- for patients who have high homocysteine levels," says cardiologist Stephen Siegel, MD, of New York University Medical Center.
"While the overall results of this study show a negative effect from these vitamins, that detrimental effect was not present in patients who had high homocysteine levels."
Another possible explanation for the study findings: At the start of Lange's study, the use of cholesterol-lowering statin drugs such as Lipitor and Zocor were used by a surprisingly low number of patients -- only 38% of those getting the vitamins and 42% of those on placebo drugs.
"And that may have been enough to shade the results," Siegel tells WebMD. These drugs are routinely prescribed to heart patients, and especially candidates for angioplasty.
Howard C. Herrmann, MD, director of interventional cardiology and cardiac catheterization laboratories at the University of Pennsylvania Medical Center, wrote an accompanying editorial to Lange's study and notes several differences between this study and the study that showed a benefit from vitamin therapy.
For one thing, higher doses of vitamin supplements were used in Lange's research, especially B-6, says Herrmann. "We don't really know the role of B-6 and B-12, other than they work together with folate to reduce homocysteine," he tells WebMD.
The people studied in the two trials were also different. The study that showed a benefit from vitamin supplement had more smokers and people with diabetes -- factors that can boost homocysteine levels. The study also showed the biggest benefit from vitamin therapy occurred in patients treated with angioplasty alone, rather than those getting angioplasty with stents. In Lange's study, all patients got stents.
Lessons to Learn
What does this all mean?
"Folate supplementation has been considered safe and completely benign," Herrmann tells WebMD. "And even if its effect on [renarrowing] wasn't as great as what was previously shown, you could still say, 'why not give it to people?' But now, there's a study that suggests it could be harmful, so we may need to rethink that."
Something else to reconsider: Priorities in treating angioplasty patients, he says. Since the 1990s, more patients have been treated with newer, second-generation stents that are coated with medication that helps prevent renarrowing, which has reduces the risk from about 20%-30% to single digits.
"[Renarrowing] is not as big an issue these days, with the advent of drug-eluting stents, so our focus should be more on preventing new cardiovascular disease," he says.