Lowering homocysteine in patients with ischemic stroke to prevent recurrent stroke, myocardial infarction, and death:...

Area of Science:

• Neurology
• Cardiovascular Medicine
• Nutritional Science

Background:

• Elevated plasma total homocysteine is linked to increased ischemic stroke risk in observational studies.
• The effectiveness of homocysteine-lowering therapy in preventing recurrent stroke remains unconfirmed by randomized trials.

Purpose of the Study:

• To evaluate if high-dose folic acid, pyridoxine (vitamin B6), and cobalamin (vitamin B12) reduce recurrent stroke risk compared to low doses.
• To assess the impact of homocysteine-lowering therapy on stroke, coronary heart disease (CHD) events, and mortality.

Main Methods:

• A double-blind randomized controlled trial involving 3680 adults with prior nondisabling cerebral infarction.
• Participants received either high-dose or low-dose formulations of folic acid, vitamin B6, and vitamin B12 alongside standard care.
• Primary outcome was recurrent cerebral infarction; secondary outcomes included CHD events and death over a 2-year period.

Main Results:

• High-dose vitamin therapy achieved a mean homocysteine reduction of 2 micromol/L greater than low-dose, but showed no significant effect on stroke, CHD, or death.
• The risk ratio for any stroke, CHD event, or death within 2 years was 1.0 (95% CI, 0.8-1.1).
• A graded association was observed between baseline homocysteine levels and vascular risk, with lower levels correlating to reduced risk of stroke, CHD events, and death.

Conclusions:

• Moderate reduction of total homocysteine via high-dose vitamin supplementation did not impact vascular outcomes within 2 years post-cerebral infarction.
• The consistent association between homocysteine levels and vascular risk suggests further research is warranted.
• Longer trials in diverse populations with elevated homocysteine may be necessary to fully explore this hypothesis.