Homocysteine lowering with folic acid and B vitamins in vascular disease.

BACKGROUND: In observational studies, lower homocysteine levels are associated with lower rates of coronary heart disease and stroke. Folic acid and vitamins B6 and B12 lower homocysteine levels. We assessed whether supplementation reduced the risk of major cardiovascular events in patients with vascular disease. METHODS: We randomly assigned 5522 patients 55 years of age or older who had vascular disease or diabetes to daily treatment either with the combination of 2.5 mg of folic acid, 50 mg of vitamin B6, and 1 mg of vitamin B12 or with placebo for an average of five years. The primary outcome was a composite of death from cardiovascular causes, myocardial infarction, and stroke. RESULTS: Mean plasma homocysteine levels decreased by 2.4 micromol per liter (0.3 mg per liter) in the active-treatment group and increased by 0.8 micromol per liter (0.1 mg per liter) in the placebo group. Primary outcome events occurred in 519 patients (18.8 percent) assigned to active therapy and 547 (19.8 percent) assigned to placebo (relative risk, 0.95; 95 percent confidence interval, 0.84 to 1.07; P=0.41). As compared with placebo, active treatment did not significantly decrease the risk of death from cardiovascular causes (relative risk, 0.96; 95 percent confidence interval, 0.81 to 1.13), myocardial infarction (relative risk, 0.98; 95 percent confidence interval, 0.85 to 1.14), or any of the secondary outcomes. Fewer patients assigned to active treatment than to placebo had a stroke (relative risk, 0.75; 95 percent confidence interval, 0.59 to 0.97). More patients in the active-treatment group were hospitalized for unstable angina (relative risk, 1.24; 95 percent confidence interval, 1.04 to 1.49). CONCLUSIONS: Supplements combining folic acid and vitamins B6 and B12 did not reduce the risk of major cardiovascular events in patients with vascular disease. (ClinicalTrials.gov number, NCT00106886; Current Controlled Trials number, ISRCTN14017017.).

Effect of long-term therapy with ramipril in high-risk women.

OBJECTIVES: We evaluated the effects of long-term therapy with the angiotensin-converting enzyme (ACE) inhibitor ramipril on major cardiovascular (CV) outcomes in high-risk women. BACKGROUND: The effect of long-term ACE inhibitor therapy in high-risk women without heart failure and with preserved left ventricular (LV) systolic function has not been previously reported. METHODS: The Heart Outcomes Prevention Evaluation (HOPE) trial is a large, randomized clinical trial that evaluated ramipril and vitamin E in high-risk patients. We present the preplanned analysis of the effects of ramipril in women in the HOPE study. The study randomized 2,480 women aged >or=55 years with vascular disease or diabetes and at least one additional CV risk factor and without heart failure or a known low LV ejection fraction to ramipril (10 mg/day) or placebo. The primary outcome was the composite of myocardial infarction, stroke or CV death. Average follow-up was 4.5 years. RESULTS: Treatment with ramipril resulted in reduced primary end point rates (11.3% vs. 14.9% in the placebo arm; relative risk [RR] 0.77, 95% confidence interval [CI] 0.62 to 0.96; p = 0.019), fewer strokes (3.1% vs. 4.8%; RR 0.64, 95% CI 0.43 to 0.96; p = 0.029) and fewer CV deaths (4.2% vs. 6.9%; RR 0.62, 95% CI 0.44 to 0.88; p = 0.0068). There were trends toward reduced rates of myocardial infarction, heart failure and all-cause death. The beneficial effect of ramipril was similar in women and men. CONCLUSIONS: Treatment with ramipril reduces the CV risk in high-risk women without heart failure and with preserved LV systolic function.