September 04, 2007

September 4, 2007 (Vienna, Austria) - Another trial has confirmed that lowering homocysteine with B vitamins does not reduce cardiovascular risk. The Western Norway B-Vitamin Intervention Trial (WENBIT), presented at the European Society of Cardiology Congress 2007 today, showed no benefit of either folate with vitamin B 12 or vitamin B 6 in patients with established heart disease. Presenting the results, Dr Marta Ebbing (Haukeland University Hospital, Bergen, Norway) said they added to previous evidence showing that B-vitamin supplementation is not justified as secondary prevention in heart disease.

However, when asked if this signaled the end of interest in homocysteine in heart disease, she replied, "It is not that simple. Homocysteine is a definite risk marker in heart disease, but it may not be causal." She added that there is still some interest in whether lowering homocysteine may have an effect on stroke and that more research in this area is warranted.

In WENBIT, 3090 CHD patients were randomized (in a 2x2 factorial design) to four groups to receive a daily oral dose of folic acid 0.8 mg (with vitamin B 12 0.4 mg) and vitamin B 6 40 mg; folic acid (with vitamin B 12) alone; vitamin B 6 alone; or placebo. After a median follow-up of 38 months, there was no significant difference in the risk of death or major cardiovascular events among the four groups.

WENBIT: Number of Patients With Cardiovascular Events

End point Folic acid+B 12+B 6 Folic acid+B 12 B 6 Placebo
All-cause death 31 33 28 25
Nonfatal MI 35 50 43 34
Unstable angina 18 27 20 22
Nonfatal stroke 9 16 15 16
Total 93 126 106 97

Ebbing noted that although no benefit was seen in this trial, the results were somewhat reassuring, in that the suggestion of possible harm seen in the NORVIT study was not replicated here.

Discussant of the trial at the hotline session, Dr Salim Yusuf (McMaster University, Hamilton, ON), pointed out that that when these results were added to previous trials, "we now have data on a total of 20,000 patients in trials of vitamin B, with no effect seen on heart disease and just a possible modest effect on stroke."

Yusuf made several possible suggestions as to why this is the case, when epidemiological evidence has shown strong associations between homocysteine levels and heart disease. He said the link between blood levels of homocysteine and heart disease could be explained by confounding factors such as renal function and that the genetic link may have been due to publication bias or, alternatively, that the trials may still not have amassed enough data to show any effect of homocysteine lowering.

But he added that this study, like previous ones, had shown a slight trend toward a reduction in stroke and that two further major trials under way would hopefully clarify whether this is a real effect or not. He added that the VITATOPS trial in 8000 stroke patients and the SEARCH trial in 12,000 heart-disease patients will more than double the total database on homocysteine lowering. Yusuf concluded that "there is no reason now to lower homocysteine levels, but it is still too early to write offthe hypothesis completely."

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