Context: Experimental and epidemiological data suggest that vitamin E supplementation may prevent cancer and cardiovascular events. Clinical trials have generally failed to confirm benefits, possibly due to their rela...Context: Experimental and epidemiological data suggest that vitamin E supplementation may prevent cancer and cardiovascular events. Clinical trials have generally failed to confirm benefits, possibly due to their relatively short duration. Objective: To evaluate whether long-term supplementation with vitamin E decreases the risk of cancer, cancer death, and major cardiovascular events. Design, Setting, and Patients: A randomized, double-blind, placebo-controlled international trial(the initial Heart Outcomes Prevention Evaluation[HOPE] trial conducted between December 21, 1993, and April 15,1999) of patients at least 55 years old with vascular disease or diabetes mellitus was extended(HOPE-The Ongoing Outcomes[HOPE-TOO]) between April 16,1999, and May 26, 2003. Of the initial 267 HOPE centers that had enrolled 9541 patients, 174 centers participated in the HOPE-TOO trial. Of 7030 patients enrolled at these centers, 916 were deceased at the beginning of the extension, 1382 refused participation, 3994 continued to take the study intervention, and 738 agreed to passive follow-up. Median duration of follow-up was 7.0 years. Intervention: Daily dose of natural source vitamin E(400 IU) or matching placebo. Main Outcome Measures: Primary outcomes included cancer incidence, cancer deaths, and major cardiovascular events(myocardial infarction, stroke, and cardiovascular death). Secondary outcomes included heart failure, unstable angina, and revascularizations. Results: Among all HOPE patients, there were no significant differences in the primary analysis: for cancer incidence, there were 552 patients(11.6%) in the vitamin E group vs 586(12.3%) in the placebo group(relative risk[RR], 0.94; 95%confidence interval[CI], 0.84-1.06; P=.30); for cancer deaths, 156(3.3%) vs 178(3.7%), respectively(RR, 0.88; 95%CI, 0.71-1.09; P=.24); and for major cardiovascular events, 1022(21.5%) vs 985(20.6%), respectively(RR, 1.04; 95%CI, 0.96-1.14; P=.34). Patients in the vitamin E group had a higher risk of heart failure(RR, 1.13; 95%CI, 1.01-1.26; P=.03) and hospitalization for heart failure(RR, 1.21; 95%CI, 1.00-1,47; P=.045). Similarly, among patients enrolled at the centers participating in the HOPE-TOO trial, there were no differences in cancer incidence, cancer deaths, and major cardiovascular events, but higher rates of heart failure and hospitalizations for heart failure. Conclusion: In patients with vascular disease or diabetes mellitus, longterm vitamin E supplementation does not prevent cancer or major cardiovascular events and may increase the risk for heart failure.展开更多
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 s...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 μmol per liter(0.3 mg per liter) in the active-treatment group and increased by 0.8 μmol 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.展开更多
文摘Context: Experimental and epidemiological data suggest that vitamin E supplementation may prevent cancer and cardiovascular events. Clinical trials have generally failed to confirm benefits, possibly due to their relatively short duration. Objective: To evaluate whether long-term supplementation with vitamin E decreases the risk of cancer, cancer death, and major cardiovascular events. Design, Setting, and Patients: A randomized, double-blind, placebo-controlled international trial(the initial Heart Outcomes Prevention Evaluation[HOPE] trial conducted between December 21, 1993, and April 15,1999) of patients at least 55 years old with vascular disease or diabetes mellitus was extended(HOPE-The Ongoing Outcomes[HOPE-TOO]) between April 16,1999, and May 26, 2003. Of the initial 267 HOPE centers that had enrolled 9541 patients, 174 centers participated in the HOPE-TOO trial. Of 7030 patients enrolled at these centers, 916 were deceased at the beginning of the extension, 1382 refused participation, 3994 continued to take the study intervention, and 738 agreed to passive follow-up. Median duration of follow-up was 7.0 years. Intervention: Daily dose of natural source vitamin E(400 IU) or matching placebo. Main Outcome Measures: Primary outcomes included cancer incidence, cancer deaths, and major cardiovascular events(myocardial infarction, stroke, and cardiovascular death). Secondary outcomes included heart failure, unstable angina, and revascularizations. Results: Among all HOPE patients, there were no significant differences in the primary analysis: for cancer incidence, there were 552 patients(11.6%) in the vitamin E group vs 586(12.3%) in the placebo group(relative risk[RR], 0.94; 95%confidence interval[CI], 0.84-1.06; P=.30); for cancer deaths, 156(3.3%) vs 178(3.7%), respectively(RR, 0.88; 95%CI, 0.71-1.09; P=.24); and for major cardiovascular events, 1022(21.5%) vs 985(20.6%), respectively(RR, 1.04; 95%CI, 0.96-1.14; P=.34). Patients in the vitamin E group had a higher risk of heart failure(RR, 1.13; 95%CI, 1.01-1.26; P=.03) and hospitalization for heart failure(RR, 1.21; 95%CI, 1.00-1,47; P=.045). Similarly, among patients enrolled at the centers participating in the HOPE-TOO trial, there were no differences in cancer incidence, cancer deaths, and major cardiovascular events, but higher rates of heart failure and hospitalizations for heart failure. Conclusion: In patients with vascular disease or diabetes mellitus, longterm vitamin E supplementation does not prevent cancer or major cardiovascular events and may increase the risk for heart failure.
文摘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 μmol per liter(0.3 mg per liter) in the active-treatment group and increased by 0.8 μmol 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.
