Norwegian Vitamin Trial - NORVIT

Description:

The goal of the trial was to evaluate treatment with high-dose vitamin B compared with placebo among patients with ST elevation myocardial infarction (MI).

Study Design

Study Design:

Patients Enrolled: 3,749
Mean Follow Up: 3.5 year follow-up
Mean Patient Age: Mean age 63 years
Female: 26

Patient Populations:

Acute MI in prior seven days, and age 30-84 years

Exclusions:

Ongoing vitamin B therapy, expected poor compliance, and other life-threatening disease

Primary Endpoints:

MI (including sudden death) or stroke

Secondary Endpoints:

Individual components of the composite, mortality, percutaneous coronary intervention, coronary artery bypass grafting, and hospitalization due to unstable angina

Drug/Procedures Used:

Patients were randomized in a factorial, double-blind manner to treatment with folic acid (0.8 mg; n=935), vitamin B6 (40 mg, n=934), both folic acid 0.8 mg and vitamin B6 40 mg (n=937) or placebo (n=943). Patients were to be treated with other standard post-MI therapy.

Principal Findings:

Concomitant medications included aspirin (89%), beta-blockers (91%), and statin therapy (81%). Homocysteine levels decreased by 28% in the folic acid groups, but did not decrease in the groups not treated with folic acid. Likewise, there was a reduction in plasma folate in the folic acid treated groups.

There was no difference in the primary composite endpoint of reinfarction or stroke in the monotherapy groups compared with placebo (70.1 per 1,000 patient-years for vitamin B6, 66.9 per 1,000 patient-years for folic acid, and 67.2 per 1,000 patient-years for placebo); however, combination therapy with both vitamin B and folic acid had a higher event rate (81.6 per 1,000 patient-years, p=0.05).

There was no difference in mortality (33.4 per 1,000 patient-years for vitamin B6, 28.7 per 1,000 patient-years for folic acid, 37.5 per 1,000 patient-years for combination and 31.7 per 1,000 patient-years for placebo) or MI (64.0, 57.5, 73.0, and 59.2 per 1,000 patient-years for vitamin B6, folic acid, combination, and placebo, respectively). Cancer was numerically but not significantly higher with folic acid (risk ratio 1.4 for folic acid groups combined vs. all others, p=0.08).

Interpretation:

Among patients with ST elevation MI, treatment with high-dose vitamin B and/or folic acid was not associated with difference in reinfarction or stroke compared with placebo.

Homocysteine levels have been shown to be higher in the setting of MI and stroke; however, it was not known if reducing homocysteine levels would reduce the occurrence of MI or stroke. The lack of difference in MI or stroke between the folic acid group and the placebo group in the present study occurred despite lowering of homocysteine levels by nearly 30%, suggesting that while homocysteine levels may correlate with occurrence of cardiac events, it is likely not a causal risk factor. Another large-scale randomized trial with folic acid and vitamin B in coronary heart disease, the HOPE-2 trial, also showed no difference in outcomes with this treatment.

References:

Harald Bonaa K, et al. Homocysteine Lowering and Cardiovascular Events after Acute Myocardial Infarction. N Engl J Med 2006;354:epub before print.

Presented by Dr. Kaare Harald Bonaa at the European Society of Cardiology Hot Line Session, September 2005.

Clinical Topics: Dyslipidemia, Atherosclerotic Disease (CAD/PAD), Nonstatins, Novel Agents, Statins

Keywords: Odds Ratio, Coronary Artery Disease, Vitamin B 6, Myocardial Infarction, Stroke, Neoplasms, Folic Acid, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Risk Factors


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