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CLINICAL QUESTION: Does vitamin E supplementation play a role in the secondary prevention of cardiovascular events in high-risk patients?
BACKGROUND: The role of the antioxidant vitamin E in primary and secondary prevention of cardiovascular disease is unclear. Observational studies suggest that vitamin E may slow the development and progression of atherosclerosis. Four published randomized controlled trials reached differing conclusions that may be partly attributed to different study designs. This investigation, as part of the Heart Outcomes Prevention Evaluation (HOPE) study, evaluates the utility of vitamin E in secondary prevention in high-risk cardiovascular patients.
POPULATION STUDIED: This study enrolled 10,576 individuals aged 55 years and older from more than 200 outpatient centers on 3 continents. Enrolled patients had known coronary artery disease, stroke, or peripheral vascular disease. Patients were also enrolled if they had diabetes and one of the following cardiovascular risk factors: hypertension, hypercholesterolemia, tobacco use, or microalbuminuria. Exclusion criteria included a known ejection fraction of less than 40%, currently taking an angiotensin-converting enzyme (ACE) inhibitor or vitamin E, having uncontrolled hypertension or overt nephropathy, or a history of myocardial infarction or stroke within 4 weeks of enrollment. Approximately 25% of the patients were women.
STUDY DESIGN AND VALIDITY: This study was designed to test the effect of vitamin E and ramipril on cardiovascular events in high-risk patients. The authors of this study report only the RESULTS: for vitamin E. Before randomization an initial run-in period with a low dose of ramipril eliminated more than 1000 participants because of noncompliance, medication side effects, or abnormal serum creatinine or potassium levels. In an adequately concealed fashion, 9541 patients were randomized in a double-blinded fashion to either 400 IU of vitamin E from natural sources or placebo. They were followed for a mean of 4.5 years with evaluation every 6 months. The vitamin E group had 89% compliance at 5 years. The study was discontinued early because of the significant benefit demonstrated in the ramipril arm (see next POEM). The study had adequate power to detect a clinically relevant reduction in the primary outcome. The diverse population characteristics of enrollees will tend to make this study’s findings applicable to many primary care patients.
OUTCOMES MEASURED: The primary outcome was the combined end point of myocardial infarction, stroke, or cardiovascular death while secondary outcomes were death from any cause, worsening congestive heart failure, unstable angina, complications associated with diabetes, or any of the individual primary end points.
RESULTS: There were no significant differences in primary or secondary outcomes between the vitamin E group and the placebo group. No differences in primary and secondary outcomes were revealed when analyzing patient subgroups defined by sex, age, previous cardiovascular disease, medication use, diabetes, tobacco use, or ramipril versus placebo use. There was also no increase in the rate of adverse effects with the vitamin E group, in particular with respect to hemorrhagic stroke.
This well-designed study provides convincing evidence that high-dose vitamin E from natural sources during a 4- to 6-year period does not reduce the incidence of cardiovascular events in high-risk patients. Observational studies have associated vitamin consumption, particularly vitamin E, with reduced incidence of coronary artery disease. In those studies it is difficult to distinguish whether the vitamin or other lifestyle factors, such as exercise or other facets of diet, contribute to this finding. This study does not address the role of vitamin E in primary prevention or comment on any benefits of longer-term use. In many centers, this study is continuing to evaluate the benefit of vitamin E for the prevention of cancer.
CLINICAL QUESTION: Does vitamin E supplementation play a role in the secondary prevention of cardiovascular events in high-risk patients?
BACKGROUND: The role of the antioxidant vitamin E in primary and secondary prevention of cardiovascular disease is unclear. Observational studies suggest that vitamin E may slow the development and progression of atherosclerosis. Four published randomized controlled trials reached differing conclusions that may be partly attributed to different study designs. This investigation, as part of the Heart Outcomes Prevention Evaluation (HOPE) study, evaluates the utility of vitamin E in secondary prevention in high-risk cardiovascular patients.
POPULATION STUDIED: This study enrolled 10,576 individuals aged 55 years and older from more than 200 outpatient centers on 3 continents. Enrolled patients had known coronary artery disease, stroke, or peripheral vascular disease. Patients were also enrolled if they had diabetes and one of the following cardiovascular risk factors: hypertension, hypercholesterolemia, tobacco use, or microalbuminuria. Exclusion criteria included a known ejection fraction of less than 40%, currently taking an angiotensin-converting enzyme (ACE) inhibitor or vitamin E, having uncontrolled hypertension or overt nephropathy, or a history of myocardial infarction or stroke within 4 weeks of enrollment. Approximately 25% of the patients were women.
STUDY DESIGN AND VALIDITY: This study was designed to test the effect of vitamin E and ramipril on cardiovascular events in high-risk patients. The authors of this study report only the RESULTS: for vitamin E. Before randomization an initial run-in period with a low dose of ramipril eliminated more than 1000 participants because of noncompliance, medication side effects, or abnormal serum creatinine or potassium levels. In an adequately concealed fashion, 9541 patients were randomized in a double-blinded fashion to either 400 IU of vitamin E from natural sources or placebo. They were followed for a mean of 4.5 years with evaluation every 6 months. The vitamin E group had 89% compliance at 5 years. The study was discontinued early because of the significant benefit demonstrated in the ramipril arm (see next POEM). The study had adequate power to detect a clinically relevant reduction in the primary outcome. The diverse population characteristics of enrollees will tend to make this study’s findings applicable to many primary care patients.
OUTCOMES MEASURED: The primary outcome was the combined end point of myocardial infarction, stroke, or cardiovascular death while secondary outcomes were death from any cause, worsening congestive heart failure, unstable angina, complications associated with diabetes, or any of the individual primary end points.
RESULTS: There were no significant differences in primary or secondary outcomes between the vitamin E group and the placebo group. No differences in primary and secondary outcomes were revealed when analyzing patient subgroups defined by sex, age, previous cardiovascular disease, medication use, diabetes, tobacco use, or ramipril versus placebo use. There was also no increase in the rate of adverse effects with the vitamin E group, in particular with respect to hemorrhagic stroke.
This well-designed study provides convincing evidence that high-dose vitamin E from natural sources during a 4- to 6-year period does not reduce the incidence of cardiovascular events in high-risk patients. Observational studies have associated vitamin consumption, particularly vitamin E, with reduced incidence of coronary artery disease. In those studies it is difficult to distinguish whether the vitamin or other lifestyle factors, such as exercise or other facets of diet, contribute to this finding. This study does not address the role of vitamin E in primary prevention or comment on any benefits of longer-term use. In many centers, this study is continuing to evaluate the benefit of vitamin E for the prevention of cancer.
CLINICAL QUESTION: Does vitamin E supplementation play a role in the secondary prevention of cardiovascular events in high-risk patients?
BACKGROUND: The role of the antioxidant vitamin E in primary and secondary prevention of cardiovascular disease is unclear. Observational studies suggest that vitamin E may slow the development and progression of atherosclerosis. Four published randomized controlled trials reached differing conclusions that may be partly attributed to different study designs. This investigation, as part of the Heart Outcomes Prevention Evaluation (HOPE) study, evaluates the utility of vitamin E in secondary prevention in high-risk cardiovascular patients.
POPULATION STUDIED: This study enrolled 10,576 individuals aged 55 years and older from more than 200 outpatient centers on 3 continents. Enrolled patients had known coronary artery disease, stroke, or peripheral vascular disease. Patients were also enrolled if they had diabetes and one of the following cardiovascular risk factors: hypertension, hypercholesterolemia, tobacco use, or microalbuminuria. Exclusion criteria included a known ejection fraction of less than 40%, currently taking an angiotensin-converting enzyme (ACE) inhibitor or vitamin E, having uncontrolled hypertension or overt nephropathy, or a history of myocardial infarction or stroke within 4 weeks of enrollment. Approximately 25% of the patients were women.
STUDY DESIGN AND VALIDITY: This study was designed to test the effect of vitamin E and ramipril on cardiovascular events in high-risk patients. The authors of this study report only the RESULTS: for vitamin E. Before randomization an initial run-in period with a low dose of ramipril eliminated more than 1000 participants because of noncompliance, medication side effects, or abnormal serum creatinine or potassium levels. In an adequately concealed fashion, 9541 patients were randomized in a double-blinded fashion to either 400 IU of vitamin E from natural sources or placebo. They were followed for a mean of 4.5 years with evaluation every 6 months. The vitamin E group had 89% compliance at 5 years. The study was discontinued early because of the significant benefit demonstrated in the ramipril arm (see next POEM). The study had adequate power to detect a clinically relevant reduction in the primary outcome. The diverse population characteristics of enrollees will tend to make this study’s findings applicable to many primary care patients.
OUTCOMES MEASURED: The primary outcome was the combined end point of myocardial infarction, stroke, or cardiovascular death while secondary outcomes were death from any cause, worsening congestive heart failure, unstable angina, complications associated with diabetes, or any of the individual primary end points.
RESULTS: There were no significant differences in primary or secondary outcomes between the vitamin E group and the placebo group. No differences in primary and secondary outcomes were revealed when analyzing patient subgroups defined by sex, age, previous cardiovascular disease, medication use, diabetes, tobacco use, or ramipril versus placebo use. There was also no increase in the rate of adverse effects with the vitamin E group, in particular with respect to hemorrhagic stroke.
This well-designed study provides convincing evidence that high-dose vitamin E from natural sources during a 4- to 6-year period does not reduce the incidence of cardiovascular events in high-risk patients. Observational studies have associated vitamin consumption, particularly vitamin E, with reduced incidence of coronary artery disease. In those studies it is difficult to distinguish whether the vitamin or other lifestyle factors, such as exercise or other facets of diet, contribute to this finding. This study does not address the role of vitamin E in primary prevention or comment on any benefits of longer-term use. In many centers, this study is continuing to evaluate the benefit of vitamin E for the prevention of cancer.