VITATOPS dampens hopes of stroke prevention with B vitamins
MedWire News: The VITATOPS trial, conducted in patients with previous stroke or transient ischemic attack (TIA), has been unable to demonstrate the putative vascular benefits of B-vitamin treatment.
In a related commentary in The Lancet Neurology, Peter Sandercock (Western General Hospital, Edinburgh, UK) said that VITATOPS (VITAmins TO Prevent Stroke) illustrates just how hard it is to prove or disprove a modest but potentially clinically important treatment effect.
The VITATOPS team also conducted a systematic review and meta-analysis of 12 trials, which showed some evidence for an 8% risk reduction with B-vitamin treatment versus placebo (confidence interval 0.84-1.00).
To confirm such an effect would require a global trial involving "several tens of thousands of patients," said Sandercock.
The VITATOPS trial itself included 8164 patients who had suffered stroke or TIA within the past 7 months. They were randomly assigned to receive a daily placebo tablet or one containing folic acid 2 mg, vitamin B6 25 mg, and vitamin B12 0.5 mg.
During 3.4 years of follow-up, 15% of patients given B vitamins and 17% of those given placebo reached the primary endpoint of stroke, myocardial infarction, or vascular death. This equated to a nonsignificant 9% relative risk reduction and a 1.56% absolute risk reduction associated with B-vitamin treatment.
A total of 1164 patients had a fasting blood test at the end of follow-up, revealing average total homocysteine levels of 10.5 versus 14.3 µmol/l in the B-vitamin and placebo groups, respectively. The 3.8-µmol/l difference between the two groups was statistically significant.
Each 1.0-µmol/l reduction in homocysteine during the trial was associated with a nonsignificant 2% reduction in risk for the primary outcome, report Graeme Hankey (Royal Perth Hospital, Australia) and team.
But Sandercock said that it is still too soon to discount the evidence from observational epidemiology and conclude that homocysteine lowering does not reduce vascular risk.
He cited examples such as antiplatelet treatment with aspirin, cholesterol lowering, and tamoxifen treatment of breast cancer where it took a long time for the cumulative weight of evidence to show the benefits of treatment.
"With that in mind, I think the jury is still out on homocysteine reduction, at least until the present trials are complete," said Sandercock.
He added: "There is still a place for further trials of homocysteine-lowering treatment, especially if the intervention can achieve and sustain large reductions in homocysteine."
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By Eleanor McDermid