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Home Research Research Line Cardiovascular Diseases Projects A multi-centre, randomised, double-blind, placebo-controlled, clinical trial examining the efficacy and safety of multi-vitamin therapy in secondary stroke prevention (VITATOPS)

Projects

A multi-centre, randomised, double-blind, placebo-controlled, clinical trial examining the efficacy and safety of multi-vitamin therapy in secondary stroke prevention (VITATOPS)
Details

a) Background

Epidemiological studies suggest that raised plasma concentrations of total homocysteine might be a risk factor for major vascular events. Whether lowering total homocysteine with B vitamins prevents major vascular events in patients with previous stroke or transient ischaemic attack is unknown. We aimed to assess whether the addition of once-daily supplements of B vitamins to usual medical care would lower total homocysteine and reduce the combined incidence of non-fatal stroke, non-fatal myocardial infarction, and death attributable to vascular causes in patients with recent stroke or transient ischaemic attack of the brain or eye

b) Aim/objective:

Primary Objective

  • To determine whether the addition of vitamin supplements (folate 2 mg, B6 25 mg, B12 500 μg) to best medical / surgical management (including modification of risk factors) will reduce the combined incidence of recurrent vascular events (stroke, myocardial infarction) and vascular death in patients with recent stroke or transient ischaemic attack (TIA)

Secondary Objectives

  • To determine whether the addition of vitamin supplements (folate 2 mg, B6 25 mg, B12 500 μg) will reduce the incidence of dementia and depression in patients with recent stroke or TIA.

 

  • To determine whether the addition of vitamin supplements (folate 2 mg, B6 25 mg, B12 500 μg) will reduce the occurrence of TIA in patients with recent stroke or TIA.
  • To determine whether the addition of vitamin supplements (folate 2 mg, B6 25 mg, B12 500 μg) will reduce the incidence of peripheral arterial disease (PAD) as measured by leg amputation in patients with recent stroke or TIA.
  • To determine whether the addition of vitamin supplements (folate 2 mg, B6 25 mg, B12 500 μg) will reduce the incidence of the primary outcome event (stroke, MI or vascular death) in patient subgroups such as those of different ethnicity and genotype.

c) Methods:

In this randomised, double-blind, parallel, placebo-controlled trial, we assigned patients with recent stroke or transient ischaemic attack (within the past 7 months) from 123 medical centres in 20 countries to receive one tablet daily of placebo or B vitamins (2 mg folic acid, 25 mg vitamin B6, and 0·5 mg vitamin B12). Patients were randomly allocated by means of a central 24-h telephone service or an interactive website, and allocation was by use of random permuted blocks stratifi ed by hospital. Participants, clinicians, carers, and investigators who assessed outcomes were masked to the assigned intervention. The primary endpoint was the composite of stroke, myocardial infarction, or vascular death. All patients randomly allocated to a group were included in the analysis of the primary endpoint.

d) Results:

Between Nov 19, 1998, and Dec 31, 2008, 8164 patients were randomly assigned to receive B vitamins (n=4089) or placebo (n=4075). Patients were followed up for a median duration of 3·4 years (IQR 2·0–5·5). 616 (15%) patients assigned to B vitamins and 678 (17%) assigned to placebo reached the primary endpoint (risk ratio [RR] 0·91, 95% CI 0·82 to 1·00, p=0·05; absolute risk reduction 1·56%, –0·01 to 3·16). There were no unexpected serious adverse reactions and no signifi cant diff erences in common adverse eff ects between the treatment groups

e) Total recruitment & no. of sites: Global  : 8,167; India: 1,421 from 23 sites

f) Conclusion:

Daily administration of folic acid, vitamin B6, and vitamin B12 to patients with recent stroke or

transient ischaemic attack was safe but did not seem to be more eff ective than placebo in reducing the incidence of major vascular events. These results do not support the use of B vitamins to prevent recurrent stroke. The results of ongoing trials and an individual patient data meta-analysis will add statistical power and precision to present estimates of the eff ect of B vitamins.

g) Publication status (Name & year):

Int J stroke- 2007, lancet Neurol 2010

h) Publication link:  

https://www.clinicalkey.com/#!/content/playContent/1-s2.0-S1474442210701873

Updated as on: 30th June 2023