VITAmins TO Prevent Stroke Research Articles

Predictors of post stroke cognitive impairment: VITATOPS cognition substudy

IntroductionPost stroke cognitive impairment (PSCI) is a common complication of ischemic stroke. PSCI can involve different depending on clinical and stroke related characteristics. The aim of this study is to determine the factors associated with impairments in specific cognitive domains. MethodsThe Vitamins to Prevent Stroke (VITATOPS) trial is a large, multinational randomised controlled trial. In this substudy, consecutive patients admitted for ischaemic stroke or transient ischaemic attack (TIA) at a tertiary hospital in Singapore were included. PSCI was defined as impairment of any of the six cognitive subgroups – visuoconstruction, attention, verbal memory, language, visual memory and visuomotor function – that were assessed annually for up to five years. Univariate and multivariate Cox proportional hazard models were used to determine factors associated with impairments in each of these cognitive domains. ResultsA total of 736 patients were included in this study, of which 173 (23.5 %) developed cognitive impairment. Out of the six cognitive domains, the greatest proportion of patients had an impairment in visuoconstruction (26.4 %) followed by attention (19.8 %), verbal memory (18.3 %), language (17.5 %), visual memory (17.3 %) and visuomotor function (14.8 %). Patients with posterior circulation cerebral infarction (POCI) as the index stroke subtype had higher rates of cognitive impairment. Further subgroup analyses show that Indian race and advanced age were predictive of language impairment, whilst fewer years of education and POCI were predictive of verbal memory impairment. POCI was predictive of visual memory impairment, and advanced age and POCI were predictive of visuomotor function impairment. ConclusionWe identified visuoconstruction and attention domains to be the most affected in our Asian cohort of PSCI. Advanced age, lower levels of education, posterior circulation strokes and concomitant comorbidities such as peripheral artery disease are independent predictors of PSCI.

Efficacy of B‐Vitamin Supplementation in Stroke and Hypertension

Stroke is the fifth leading cause of death in the United States, and hypertension is the leading risk factor for stroke. However, pharmacologic therapies have been shown to reduce stroke‐related complications, and nutrient supplementation is increasingly used in the stroke prevention treatment plan. This study aimed to collect and summarize evidence on the efficacy of B‐vitamin supplementation in the prevention and treatment of stroke and hypertension. Based on a preliminary literature search, it was predicted that B‐vitamin supplementation helps prevent stroke in hypertensive patients. A systematic review was conducted, searching through PubMed databases for randomized control trials (RCTs) of B‐vitamin interventions (vitamin B complex, vitamin B6, vitamin B12, riboflavin, thiamine, niacin, folic acid, or folate) and stroke and hypertension outcomes (hypertension, stroke, high blood pressure, vascular stiffness, or arterial stiffness). After search and screening by two independent individuals, we identified 69 RCTs for inclusion in the review. There are 30 RCTs with a direct B‐vitamin intervention and stroke and hypertension outcome relationship, 26 RCTs with an indirect relationship, 2 RCTs that came from the Vitamin Intervention for Stroke Prevention (VISP) Trials, 3 RCTs from the VITAmins TO Prevent Stroke (VITATOPS), 8 RCTs from the China Stroke Primary Prevention Trial. Preliminary findings reveal that folic acid supplementation was associated with a significant benefit in reducing the risk of stroke in hypertensive patients and a decrease in homocysteine concentrations. Concluding findings contribute to current knowledge regarding the use of B vitamin supplements in chronic disease prevention.

Homocysteine Lowering with B Vitamins for Stroke Prevention—A History

Early trials of B vitamin therapy to lower plasma total homocysteine (tHcy) reported no reduction of stroke with high doses of folate/B6 and cyanocobalamin 400–1,000 μg daily. In patients with diabetic nephropathy, folate/B6 and cyanocobalamin 1,000 μg daily accelerated the decline of renal function and doubled cardiovascular events. Patients with renal failure have high cyanide levels. The French SUpplementation with FOlate, vitamin B6 and B12 and/or OMega-3 fatty acids (Su.Fol.OM3) trial—with the best renal function of the early trials and the lowest dose of cyanocobalamin (20 μg daily)—reported a 43% reduction of stroke. Then the China Stroke Primary Prevention Trial (CSPPT) reported that folic acid alone reduced stroke and was beneficial even in patients with impaired renal function. Patient-level data from the Vitamin Intervention to Prevent Stroke (VISP) and VITAmins TO Prevent Stroke (VITATOPS) trials and meta-analyses stratified by renal function and dose of cyanocobalamin confirmed that harm from cyanocobalamin among participants with renal impairment obscured the benefit of B vitamins in the early trials. It does seem that B vitamins reduce the risk of stroke. In the era of folate fortification, B12 is the main nutritional determinant of tHcy, and metabolic B12 deficiency is very common and usually missed. Therefore, folate alone is not the optimal way to lower tHcy: the use of folate (and possibly B6) with methylcobalamin or oxocobalamin should be considered.

Effect of B-vitamins on stroke risk among individuals with vascular disease who are not on antiplatelets: A meta-analysis.

Retrospective analyses of randomized controlled trials suggest that antiplatelet therapy may modify the potential cerebrovascular benefits of lowering homocysteine with B-vitamins among individuals with cardiovascular disease. We evaluated the effects of B-vitamin supplementation on risk of subsequent stroke among high cardiovascular risk individuals who are not taking antiplatelet medications. We systematically searched the Cochrane Central Register of controlled trials, PubMed, the Internet Stroke Center stroke trials, and the clinical trials.gov website from 1966 to April 2015. Inclusion criteria included: randomized controlled trials of homocysteine-lowering therapy with B-vitamins; high cardiovascular risk population and follow-up ≥1 year. We considered stroke as the primary outcome. Among 11 randomized controlled trials meeting inclusion criteria, three studies assessed stroke as an outcome and reported event rates according to whether or not individuals were taking antiplatelets: Vitamin Intervention for Stroke Prevention (VISP), VITAmins TO Prevent Stroke (VITATOPS), and Heart Outcomes Prevention Evaluation 2 (HOPE-2). A total of 4643 high vascular risk subjects not taking antiplatelets were evaluated. The overall effect size across studies was summarized using the fixed effects model after confirming there was no significant heterogeneity. Heterogeneity was assessed using the Cochran's Q and I(2) statistics. Compared with the control group, those taking B-vitamin supplementation had a lower risk of recurrent stroke (HR 0.86, 95% CI 0.62 to 1.19 for VISP; 0.65, 0.46 to 0.91 for VITATOPS; and 0.60, 0.39 to 0.92 for HOPE-2; overall HR 0.71, 0.58 to 0.88). Homocysteine lowering with B-vitamins among high vascular risk patients who are not taking antiplatelet therapy is related to a significant reduction (29%) in overall stroke risk. A clinical trial of B-vitamins in this group may be warranted.

Effect of B Vitamins and Lowering Homocysteine on Cognitive Impairment in Patients With Previous Stroke or Transient Ischemic Attack

High plasma total homocysteine (tHcy) has been associated with cognitive impairment but lowering tHcy with B-vitamins has produced equivocal results. We aimed to determine whether B-vitamin supplementation would reduce tHcy and the incidence of new cognitive impairment among individuals with stroke or transient ischemic attack≥6 months previously. A total of 8164 patients with stroke or transient ischemic attack were randomly allocated to double-blind treatment with one tablet daily of B-vitamins (folic acid, 2 mg; vitamin B6, 25 mg; vitamin B12, 500 μg) or placebo and followed up for 3.4 years (median) in the VITAmins TO Prevent Stroke (VITATOPS) trial. For this prespecified secondary analysis of VITATOPS, the primary outcome was a new diagnosis of cognitive impairment, defined as a Mini-Mental State Examination (MMSE) score<24 on ≥2 follow-up visits. Secondary outcomes were cognitive decline, and the mean tHcy and MMSE at final follow-up. A total of 3089 participants (38%) voluntarily undertook the MMSE>6 months after the qualifying stroke; 2608 participants were cognitively unimpaired (MMSE≥24), of whom 2214 participants (1110 B-vitamins versus 1104 placebo) had follow-up MMSEs during 2.8 years (median). At final follow-up, allocation to B-vitamins, compared with placebo, was associated with a reduction in mean tHcy (10.2 μmol/L versus 14.2 μmol/L; P<0.001) but no change from baseline in the mean MMSE score (-0.22 points versus -0.25 points; difference, 0.03; 95% confidence interval, -0.13 to 0.19; P=0.726) and no difference in the incidence of cognitive impairment (5.51% versus 5.47%; risk ratio, 1.01; 95% confidence interval, 0.69-1.48; P=0.976), cognitive decline (9.1% versus 10.3%; risk ratio, 0.89; 0.67-1.18; P=0.414), or cognitive impairment or decline (11.0% versus 11.3%; risk ratio, 0.98; 0.75-1.27; P=0.855). Daily supplementation with folic acid, vitamin B6, and vitamin B12 to a self-selected clinical trial cohort of cognitively unimpaired patients with previous stroke or transient ischemic attack lowered mean tHcy but had no effect on the incidence of cognitive impairment or cognitive decline, as measured by the MMSE, during a median of 2.8 years. URL: http://www.controlled-trials.com. Unique identifier: ISRCTN74743444; URL: http://www.clinicaltrials.gov. Unique identifier: NCT00097669.

Abstract 173: Effect Of B-Vitamins On Cognition In Patients With Prior Stroke

High serum total homocysteine (tHcy) and stroke are associated with increased risks of cognitive decline and cognitive impairment. This study aimed to determine whether B-vitamin treatment would reduce the risk of cognitive decline and cognitive impairment among individuals with recent stroke or transient ischemic attack (TIA) of the brain. Methods: 8,164 patients with recent stroke or TIA (&lt; 7 months) were randomly allocated to double-blind treatment with one tablet daily of placebo or B-vitamins (folic acid 2 mg, vitamin B 6 25 mg, vitamin B 12 500 μg) and followed for a median of 3.4 years for the occurrence of stroke, myocardial infarction or death due to vascular causes in the VITAmins TO Prevent Stroke (VITATOPS) trial. The Mini-Mental State Examination (MMSE) score was undertaken at least 6 months after the qualifying stroke (baseline) and every 6 months thereafter for the duration of follow-up. The primary outcome for this pre-specified secondary analysis was the composite of a decline of 3 or more points in the MMSE score compared with the baseline score at &gt; 6 months after the qualifying stroke (cognitive decline) or a new MMSE score &lt; 24 (cognitive impairment). Results: Among the 2214 participants who undertook the MMSE at least 6 months after the qualifying stroke event, and who were not cognitively impaired (MMSE &gt; 24), and who underwent repeat MMSE assessments over a median of 2.8 years, there was no significant difference in the incidence of cognitive decline or cognitive impairment among participants assigned B-vitamins compared with placebo (24.6% vs 21.7%; risk ratio [RR]: 1.13, 95% confidence interval [CI]: 0.97 to 1.32 ; p=0.1113) and no difference in cognitive decline alone (22.7% vs 20.7%; RR: 1.10, 95% CI: 0.94 to 1.19; p=0.2417). These results were consistent among clinical subgroups. From baseline (at 6 months post-stroke), the MMSE score decreased by a mean of 0.22 (SD 1.82) among participants assigned B-vitamins vs 0.25 (SD 2.08) among participants assigned placebo (p=0.7258). Conclusion: Daily administration of folic acid, vitamin B 6 and vitamin B 12 to non-demented patients with previous stroke or TIA for a median of 2.8 years had no significant effect, compared with placebo, on the rate of cognitive decline or incidence of cognitive impairment.

B Vitamins and Magnetic Resonance Imaging–Detected Ischemic Brain Lesions in Patients With Recent Transient Ischemic Attack or Stroke

Background and Purpose— Elevated concentrations of homocysteine are associated with cerebral small vessel disease (CSVD). b-vitamin supplementation with folate and vitamins b 12 and b 6 reduces homocysteine concentrations. In a substudy of the VITAmins TO Prevent Stroke (VITATOPS) trial, we assessed the hypothesis that the addition of once-daily supplements of b vitamins would reduce the progression of CSVD-related brain lesions. Methods— A total of 359 patients with recent stroke or transient ischemic attack, who were randomly allocated to double-blind treatment with placebo or b vitamins, underwent brain MRI at randomization and after 2 years of b-vitamin supplementation. MR images were analyzed blinded to treatment allocation. Outcomes related to the prespecified hypothesis were progression of white matter hyperintensities and incident lacunes. We also explored the effect of b-vitamin supplementation on the incidence of other ischemic abnormalities. Results— After 2 years of treatment with b vitamins or placebo, there was no significant difference in white matter hyperintensities volume change (0.08 vs 0.13cm 3 ; P =0.419) and incidence of lacunes (8.0% vs 5.9%, P =0.434; odds ratio=1.38). In a subanalysis of patients with MRI evidence of severe CSVD at baseline, b-vitamin supplementation was associated with a significant reduction in white matter hyperintensities volume change (0.3 vs 1.7cm 3 ; P =0.039). Conclusions— Daily b-vitamin supplementation for 2 years did not significantly reduce the progression of brain lesions resulting from presumed CSVD in all patients with recent stroke or transient ischemic attack but may do so in the subgroup of patients with recent stroke or transient ischemic attack and severe CSVD. Clinical Trial Registration— http://vitatops.highway1.com.au/ . Unique identifier: NCT00097669 and ISRCTN74743444.

Antiplatelet therapy and the effects of B vitamins in patients with previous stroke or transient ischaemic attack: a post-hoc subanalysis of VITATOPS, a randomised, placebo-controlled trial

SummaryBackgroundPrevious studies have suggested that any benefits of folic acid-based therapy to lower serum homocysteine in prevention of cardiovascular events might be offset by concomitant use of antiplatelet therapy. We aimed to establish whether there is an interaction between antiplatelet therapy and the effects of folic acid-based homocysteine-lowering therapy on major vascular events in patients with stroke or transient ischaemic attack enrolled in the vitamins to prevent stroke (VITATOPS) trial.MethodsIn the VITATOPS trial, 8164 patients with recent stroke or transient ischaemic attack were randomly allocated to double-blind treatment with one tablet daily of placebo or B vitamins (2 mg folic acid, 25 mg vitamin B6, and 500 μg vitamin B12) and followed up for a median 3·4 years (IQR 2·0–5·5) for the primary composite outcome of stroke, myocardial infarction, or death from vascular causes. In our post-hoc analysis of the interaction between antiplatelet therapy and the effects of treatment with B vitamins on the primary outcome, we used Cox proportional hazards regression before and after adjusting for imbalances in baseline prognostic factors in participants who were and were not taking antiplatelet drugs at baseline and in participants assigned to receive B vitamins or placebo. We also assessed the interaction in different subgroups of patients and different secondary outcomes. The VITATOPS trial is registered with ClinicalTrials.gov, number NCT00097669, and Current Controlled Trials, number ISRCTN74743444.FindingsAt baseline, 6609 patients were taking antiplatelet therapy and 1463 were not. Patients not receiving antiplatelet therapy were more likely to be younger, east Asian, and disabled, to have a haemorrhagic stroke or cardioembolic ischaemic stroke, and to have a history of hypertension or atrial fibrillation. They were less likely to be smokers and to have a history of peripheral artery disease, hypercholesterolaemia, diabetes, ischaemic heart disease, and a revascularisation procedure. Of the participants taking antiplatelet drugs at baseline, B vitamins had no significant effect on the primary outcome (488 patients in the B-vitamins group [15%] vs 519 in the placebo group [16%]; hazard ratio [HR] 0·94, 95% CI 0·83–1·07). By contrast, of the participants not taking antiplatelet drugs at baseline, B vitamins had a significant effect on the primary outcome (123 in the B-vitamins group [17%] vs 153 in the placebo group [21%]; HR 0·76, 0·60–0·96). The interaction between antiplatelet therapy and the effect of B vitamins on the primary outcome was significant after adjusting for imbalance in the baseline variables (adjusted p for interaction=0·0204).InterpretationOur findings support the hypothesis that antiplatelet therapy modifies the potential benefits of lowering homocysteine with B-vitamin supplementation in the secondary prevention of major vascular events. If validated, B vitamins might have a role in the prevention of ischaemic events in high-risk individuals with an allergy, intolerance, or lack of indication for antiplatelet therapy.FundingAustralia National Health and Medical Research Council, UK Medical Research Council, Singapore Biomedical Research Council, and Singapore National Medical Research Council.

The Role of Vitamin B in Stroke Prevention

> All truths are easy to understand once they are discovered; the point is to discover them. > > —Galileo Galilei (1564 to 1642), Italian physicist, astronomer, and philosopher The role of vitamins in stroke prevention has been studied for decades. Folate and cyanocobalamin (vitamin B12) are important regulators of the metabolism of homocysteine. Studies have shown that low levels of these factors are associated with elevation of homocysteine in the blood.1,2 Hyperhomocysteinemia has been associated with premature atherosclerosis with an increased risk of cardiovascular events.3,–,5 On the basis of epidemiological studies, clinicians and scientists expected that homocysteine-lowering therapy (HLT) with appropriate doses of folic acid, Vitamin B6, and Vitamin B12 supplementation would reduce the incident risk of cardiovascular diseases (including stroke). As a result, HLT has been tested in several double-blind, randomized controlled trials (Table 1).6,–,15 View this table: Table 1. Baseline Characteristics of Participants in Double-Blind, Randomized Controlled Trials of Vitamin Therapy I discuss the results of the recently published VITAmins TO Prevent Stroke (VITATOPS) trial in the context of the current available evidence.15 Needless to say, this article is not a comprehensive review, but rather it intends to highlight some of the current and relevant aspects of Vitamin B supplementation for stroke prevention. As such, several questions will remain to be answered. ### The VITATOPS Trial VITATOPS was a double-blind, placebo-controlled trial, in which 8164 patients with a recent stroke or transient ischemic attack were randomized to receive placebo or 2 mg folic acid, 25 mg Vitamin B6, and 0.5 mg Vitamin B12 in a single tablet.15 Follow-up ranged to nearly 12 years with a median of 3.5 years. The qualifying events were ischemic (88%), hemorrhagic (10%), and unknown (2%). Of the ischemic events, large artery disease was the most common stroke mechanism, and approximately one third of patients had small vessel disease. …

Advances in Emerging Therapies 2010

In 2010, there were significant advancements in stroke prevention, whereas there were fewer studies that unearthed new ground on treatment of acute stroke and rehabilitation. We first discuss important pivotal studies in stroke prevention followed by acute treatment and rehabilitation. ### Prevention #### Homocysteine, Folic Acid, and B Vitamins Approximately 90% of all strokes are attributable to vascular risk factors.1 Homocysteine has also been identified as another risk factor for stroke. VITAmins TO Prevent Stroke (VITATOPS) aimed to assess whether daily administration of folic acid, vitamin B6, and vitamin B12 in patients with recent stroke or transient ischemic attack lowers homocysteine and reduces major vascular events. The data overall and pooled analysis of individual patient data showed that B vitamins have no or at most a marginal positive effect on reducing vascular events.2 #### Blood Pressure There is a correlation between blood pressure levels and risk of stroke. Data from Rothwell and colleagues now show that not only blood pressure levels, but also blood pressure variability account for stroke risk. A meta-analysis of antihypertensive drug trials found that calcium channel blockers and nonloop diuretic drugs were more effective than other antihypertensive agents to reduce blood pressure variability.3 Drug-class effects on interindividual variation in blood pressure can explain differences in effects of antihypertensive drugs on risk of stroke independently of their effects on mean systolic blood pressure. This means that the ideal antihypertensive agent should lower both blood pressure levels and variation in blood pressure to reduce stroke risk; however, we currently do not have such agents in our pharmacopeia for stroke prevention. #### Antithrombotic Drugs and Cerebrovascular Diseases New data have emerged on some age old questions about carotid dissection and intracranial stenosis. The use of aspirin or anticoagulation in spontaneous carotid artery dissection is a matter of debate with little data to guide decision-making. Data within a nonrandomized study suggest that the frequency …

Homocysteine

The authors of the much publicized though not yet published Norwegian Vitamin Study (NORVIT)1 of vitamin therapy in coronary artery disease, are widely quoted as saying that vitamin therapy for lowering plasma total homocysteine (tHcy) was harmful, and that “homocysteine is dead.” However, the slides of their presentation1 do not show the B12 status of the participants, nor do they indicate whether B12 injections were given to participants with low levels of B12. Commentators2 have called NORVIT “the largest trial to date to test the hypothesis that folate supplementation reduces risk of cardiovascular disease,” but because there were 4 treatment arms in NORVIT, each with 900 participants, the number of patients randomized to folate/B12 or folate/B12/B6 was essentially the same as that in the Vitamin Intervention for Stroke Prevention (VISP) trial3 (≈1800). They used a much higher dose of B6 than other studies and cannot exclude the possibility that their results were driven by that choice. As did VISP, they also used a dose of B12 that, as has recently become apparent, was too low for adequate absorption of B12 in elderly subjects (discussed below). In this issue of Stroke , a substudy of the Vitamins to Prevent Stroke (VITATOPS) trial4 reports that in Singapore, treatment with 2.5 mg folic acid, 0.5 mg vitamin B12, and 25 mg B6 reduced levels of tHcy by 3.8 μmol/L compared with placebo.5 The authors also studied 2 polymorphism …

Sustained Homocysteine-Lowering Effect over Time of Folic Acid-Based Multivitamin Therapy in Stroke Patients despite Increasing Folate Status in the Population

Background and Aims: It is uncertain what impact increasing voluntary folate fortification may be having on the statistical power of randomized trials testing the homocysteine hypothesis of atherothrombosis. The objective of this study was to determine whether there has been a change in folate status between 1998 and 2002 in stroke patients randomized into the VITAmins TO Prevent Stroke (VITATOPS) Study at a single center in Perth, Australia, and what impact this may have had on the magnitude of the homocysteine-lowering effect achieved over time with folic acid-based multivitamin therapy. Methods: We conducted a randomized, double-blind, placebo-controlled study involving 285 patients with stroke or transient ischemic attack who were recruited between 1998 and 2002 and randomized to long-term folic acid 2.0 mg/day, pyridoxine 25 mg/day and cobalamin 0.5 mg/day (active VITATOPS medication) or placebo. Fasting plasma total homocysteine, red cell folate, serum cobalamin and serum pyridoxine levels were measured at baseline and 6 months, and the change in blood levels over 4 time quartiles and differences in levels between the two randomized treatments were examined. Results: Between 1998 and 2002, there was a significant rise in baseline mean red cell folate levels over 4 time quartiles among the entire stroke cohort (723.3, 780.1, 922.6 and 1,023.7 nmol/l in the first, second, third and fourth quartiles, respectively; p < 0.0001), but this was not associated with a spontaneous reduction in mean baseline total homocysteine levels during the same time period (12.7, 14.3, 12.1 and 12.8 µmol/l in the first, second, third and fourth quartiles, respectively; p = 0.55). The homocysteine-lowering effect of the active VITATOPS trial medication at 6 months after randomization also did not change significantly between 1998 and 2002 (difference between randomized groups: –4.1, –4.1, –3.1 and –3.6 µmol/l in the first, second, third and fourth quartiles, respectively; p = 0.56). Conclusions: The homocysteine-lowering effect of the active VITATOPS trial medication has not attenuated significantly in the past 5 years despite increasing voluntary fortification of foods with folic acid as reflected by a progressive rise in baseline folate status. These data suggest that in the continuing absence of a program of mandatory folate fortification of food in populations served by centers participating in the VITATOPS trial, the study will remain adequately powered to test the homocysteine-lowering hypothesis for which it was designed.

Folic acid-based multivitamin therapy to prevent stroke: the jury is still out.

There is a large body of observational and laboratory evidence suggesting but not proving that increasing plasma concentrations of total homocysteine (tHcy) is a causal risk factor for atherothromboembolic ischemic stroke and other vascular events.1–9 Recent publication of the results of the landmark Vitamins in Stroke Prevention (VISP) Trial is the first evidence from a large randomized controlled trial (RCT) of the effect of lowering tHcy via folic acid–based multiple B vitamin supplementation on the incidence of “hard” clinical events, such as recurrent stroke, in patients with recent ischemic stroke.10,11 In contrast to what was expected from the epidemiological evidence, the VISP Trial did not identify a significant treatment effect of lowering tHcy by vitamin therapy on recurrent stroke, coronary events, or death, despite confirming a consistent and graded association between baseline tHcy and vascular risk (particularly the probability of stroke over time).11 Recruiting primarily from North America, VISP enrolled 3680 recent (3 to 120 days) survivors of nondisabling, noncardiogenic, ischemic stroke with baseline tHcy above the 25th percentile of the North American stroke population into a double-blind, randomized comparison of high versus low doses of a combination of 12 different vitamins, including folic acid, vitamin B12, vitamin B6, and riboflavin, which are cofactors for enzymes responsible for metabolizing homocysteine.11 After 2 years of follow-up, there was no significant difference in the cumulative incidence of the primary outcome event of recurrent cerebral infarction: 8.4% of 1814 patients who were allocated to high-dose multivitamins [including 2.5 mg of folic acid, 0.4 mg of vitamin B12, and 25 mg of vitamin B6] versus 8.1% of 1835 patients allocated to low-dose multivitamins [including 0.02 mg of folic acid, 0.006 mg of vitamin B12, 0.2 mg of vitamin B6 …

Vitamin intervention for stroke prevention

Vitamin Intervention for Stroke Prevention (VISP) is designed to determine whether the utilization of folic acid, vitamins B 6 and B 12, in addition to other risk factor reducing measures, have a demonstrable effect on prevention of recurrent stroke. The entry criteria are a first-ever nondisabling stroke, the patient signs informed consent with willingness to participate and randomization to a high- or low-dose vitamin intervention regimen. Case acquisition of 3688 individuals has been completed, half in the high-dose and the other half in the low-dose intervention arm. Follow-up is in progress and the end results are expected within the year. The Vitamins to Prevent Stroke (VITATOPS) is a parallel study based in Australia with similar goals, and, hopefully, the data from the two will be comparable and supportive.