Heart Outcomes Prevention Evaluation - HOPE-2

Description:

The goal of the trial was to evaluate the effect of treatment with homocysteine-lowering vitamins, folic acid, and vitamin B on cardiovascular outcomes among patients with pre-existing cardiovascular disease or diabetes.

Study Design

Study Design:

Patients Enrolled: 5,522
Mean Follow Up: Mean, 5 years
Mean Patient Age: Men age 69 years
Female: 28

Patient Populations:

Age ≥55 years with a history of vascular disease (coronary, cerebrovascular, or peripheral vascular) or diabetes and additional risk factors for atherosclerosis

Exclusions:

Use of vitamin supplements containing more than 0.2 mg of folic acid per day

Primary Endpoints:

Composite of cardiovascular death, MI, and stroke

Drug/Procedures Used:

Patients were randomized in a double-blind manner to placebo (n = 2,764) or active treatment with 2.5 mg folic acid, 50 mg vitamin B6, and 1 mg vitamin B12 (n = 2,758). Patients were followed for 5 years.

Principal Findings:

Baseline characteristics were well balanced between groups, with 83% of patients having a history of cardiovascular disease and 40% diabetes. Baseline homocysteine levels were 12.2 µmol/L. At 2 years, homocysteine levels were reduced to 9.9 µmol/L in the active treatment group.

There was no difference in the primary endpoint of cardiovascular death, myocardial infarction (MI), or stroke (18.8% for vitamin group vs. 19.8% for placebo; relative risk [RR], 0.95; p = 0.41). There was also no difference in the individual components of cardiovascular death (10.0% vs. 10.5%; RR, 0.96; p = 0.59) or MI (12.4% vs. 12.6%; RR, 0.98; p = 0.82), but stroke was lower in the vitamin group (4.0% vs. 5.3%; RR, 0.75; p = 0.03). Neither occurrence of cancer (13.0% vs. 12.3%; RR, 1.06; p = 0.47) nor cancer death (3.4% each) differed between treatment groups. There was also no difference in total mortality (17.0% vs. 17.2%; RR, 0.99; p = 0.94).

Interpretation:

Among patients with pre-existing cardiovascular disease or diabetes, treatment with homocysteine-lowering vitamins, folic acid, and vitamin B were not associated with a reduction in the composite of death, MI, or stroke at 5-year follow-up compared with placebo.

Despite reducing homocysteine concentrations by approximately 25%, there was no apparent benefit with folic acid and vitamin B treatment on cardiovascular events, with the exception of a reduction in stroke in the active treatment group. Earlier epidemiological studies demonstrated that high homocysteine levels were associated with increased risk for cardiovascular diseases.

Unlike earlier observational findings, this large-scale randomized trial demonstrated little benefit on cardiovascular events, despite effectively lowering homocysteine levels, the hypothesized mechanism of action. These results are similar to those of the NORVIT trial, which also showed no effect on clinical outcomes even in the presence of reduced homocysteine levels among patients with ST elevation MI.

References:

Presented by Dr. Eva M. Lonn at the March 2006 ACC Annual Scientific Session, Atlanta, GA and the European Society of Cardiology Scientific Congress, September 2006.

Lonn E, Yusuf S, Arnold MJ, et al., on behalf of the HOPE-2 Investigators. Homocysteine lowering with folic acid and B vitamins in vascular disease. N Engl J Med 2006;354:1567-77.

Clinical Topics: Statins

Keywords: Vitamin B 6, Myocardial Infarction, Stroke, Follow-Up Studies, Atherosclerosis, Folic Acid, Risk Factors, Vitamin B 12, Diabetes Mellitus


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