Vitamin Therapy for Prevention of Stroke

Inclusion Criteria:

• Any stroke (non-disabling cerebral infarction, NDCI) < 120 days prior to randomization

• Symptoms lasting > 24 hrs, or if < 24 hrs, CT or MRI shows new infarction at expectedsite

• Modified Rankin score < 3

• Homocysteine level > the 25th percentile, ie, 9.5 mol/L for men, and 8.5 mol/L forwomen

• Patient compliance with multivitamin during run-in phase > 75%

Exclusion Criteria:

• Stroke due to: intracranial hemorrhage, dissection of a cervico-cephalic artery,veno-occlusive disease, drug abuse, vasculitis

• CT or MRI shows lesion other than infarction as cause of syndrome

• Modified Rankin score of 4 or 5 at eligibility

• Presence of potential sources of cardiogenic emboli: atrial fibrillation, prostheticcardiac valve, intracardiac thrombus or neoplasm, valvular vegetation

• Neurologic illness other than stroke that would prevent proper evaluation of recurrentstroke

• Illness that limits life expectancy to < 2 years

• Severe congestive heart failure

• Renal insufficiency requiring dialysis

• Untreated B12 deficiency or untreated pernicious anemia

• Uncontrolled hypertension (systolic >185 mm/Hg or diastolic >105 mm/Hg on two readingsseparated by 5 min.) at eligibility

• Conditions preventing reliable participation in study: refractory depression, severecognitive impairment, alcoholism, other substance abuse

• Medications given within last 30 days that affect homocysteine: methotrexate,tamoxifen, L-dopa, phenytoin, or bile acid sequestrants that can decrease folatelevels

• Women of childbearing potential

• Patients receiving active intervention in another trial

• Patients on multi-vitamins, single B6, or folic acid, unless willing to discontinueand take study supplement

• Any surgical procedure, invasive cardiac instrumentation, endarterectomy, stentplacement, thrombectomy or other endovascular treatment of abnormal carotid arteryperformed within 30 days prior to randomization or scheduled within 30 days afterrandomization