What is the relative cardiovascular benefit of lowering cholesterol, blood pressure, and glucose levels in patients with type 2 diabetes?

ABSTRACT

BACKGROUND: Type 2 diabetes is increasingly recognized as a powerful risk factor for coronary artery disease (CAD) events. In its recommendations for treating cholesterol levels, the Third Adult Treatment Panel of the National Cholesterol Education Program (NCEP) considers diabetes mellitus the equivalent of preexisting CAD.¹ The United Kingdom Prospective Diabetes Study (UKPDS) showed that blood pressure control had a greater overall effect on diabetes-related morbidity and mortality than did intensive glucose control.² The study under consideration examines data from the major trials of cardiovascular risk reduction to determine the relative benefit of controlling blood pressure and cholesterol and glucose levels in patients with type 2 diabetes.

POPULATION STUDIED: Adult patients with diabetes who participated in a variety of studies looking at reduction of risk factors for CAD.

STUDY DESIGN AND VALIDITY: This meta-analysis combined data from previous studies of intensive coronary risk factor reduction in patients with diabetes. The authors searched MEDLINE from 1966 to 2001 for articles published on the topic in English. Studies were included if they were randomized controlled trials of adults that included some patients with diabetes, compared intensive risk factor reduction with drug therapy versus either placebo or routine care, had at least 1 year of follow-up, and reported the requisite cardiovascular outcomes. The studies were independently reviewed by 2 authors for inclusion in the analysis based on these inclusion criteria; disagreement was resolved by consensus. There was no explicit validity assessment of the articles. Data were abstracted in a structured manner. The results were analyzed for heterogeneity and pooled appropriately.

OUTCOMES MEASURED: The outcomes measured included “aggregate cardiac events” (CAD death and nonfatal myocardial infarction [MI]), cardiovascular mortality, MI, and stroke. The results are presented in changes in rates over person-years and as person-years needed to treat. This was done to account for the variable lengths of patient follow-up in these large trials; these findings can be interpreted similarly to standard event rates and numbers needed to treat (NNT). One caveat is that to report an outcome for cholesterol lowering and blood pressure control across a time span of only 1 person-year is artificial, given that most changes in outcomes produced by these therapies take several years to manifest themselves.

RESULTS: Cholesterol lowering (a total of 5 studies of both primary and secondary prevention) reduced aggregate cardiac events (30 vs 41 events per 1000 person-years, NNT for 1 year 106, 95% confidence interval [CI} 62-366). Cholesterol lowering as secondary prevention contributed most to this result (3 trials, 34 vs 44 events per 1000 person-years, NNT for 1 year 120, 95% CI, 61-4856); the results of primary prevention through cholesterol lowering did not reach statistical significance. Blood pressure reduction also reduced aggregate cardiac events (17 vs 23 per 1000 person-years, NNT for 1 year 157, 95% CI, 88-726). Two trials of blood glucose reduction as primary prevention failed to show a significant difference in aggregate cardiac events. The individual cardiac outcomes (cardiovascular mortality and MI each alone) showed results consistent with the aggregate outcomes.

ABSTRACT

BACKGROUND: Type 2 diabetes is increasingly recognized as a powerful risk factor for coronary artery disease (CAD) events. In its recommendations for treating cholesterol levels, the Third Adult Treatment Panel of the National Cholesterol Education Program (NCEP) considers diabetes mellitus the equivalent of preexisting CAD.¹ The United Kingdom Prospective Diabetes Study (UKPDS) showed that blood pressure control had a greater overall effect on diabetes-related morbidity and mortality than did intensive glucose control.² The study under consideration examines data from the major trials of cardiovascular risk reduction to determine the relative benefit of controlling blood pressure and cholesterol and glucose levels in patients with type 2 diabetes.

POPULATION STUDIED: Adult patients with diabetes who participated in a variety of studies looking at reduction of risk factors for CAD.

STUDY DESIGN AND VALIDITY: This meta-analysis combined data from previous studies of intensive coronary risk factor reduction in patients with diabetes. The authors searched MEDLINE from 1966 to 2001 for articles published on the topic in English. Studies were included if they were randomized controlled trials of adults that included some patients with diabetes, compared intensive risk factor reduction with drug therapy versus either placebo or routine care, had at least 1 year of follow-up, and reported the requisite cardiovascular outcomes. The studies were independently reviewed by 2 authors for inclusion in the analysis based on these inclusion criteria; disagreement was resolved by consensus. There was no explicit validity assessment of the articles. Data were abstracted in a structured manner. The results were analyzed for heterogeneity and pooled appropriately.

OUTCOMES MEASURED: The outcomes measured included “aggregate cardiac events” (CAD death and nonfatal myocardial infarction [MI]), cardiovascular mortality, MI, and stroke. The results are presented in changes in rates over person-years and as person-years needed to treat. This was done to account for the variable lengths of patient follow-up in these large trials; these findings can be interpreted similarly to standard event rates and numbers needed to treat (NNT). One caveat is that to report an outcome for cholesterol lowering and blood pressure control across a time span of only 1 person-year is artificial, given that most changes in outcomes produced by these therapies take several years to manifest themselves.

RESULTS: Cholesterol lowering (a total of 5 studies of both primary and secondary prevention) reduced aggregate cardiac events (30 vs 41 events per 1000 person-years, NNT for 1 year 106, 95% confidence interval [CI} 62-366). Cholesterol lowering as secondary prevention contributed most to this result (3 trials, 34 vs 44 events per 1000 person-years, NNT for 1 year 120, 95% CI, 61-4856); the results of primary prevention through cholesterol lowering did not reach statistical significance. Blood pressure reduction also reduced aggregate cardiac events (17 vs 23 per 1000 person-years, NNT for 1 year 157, 95% CI, 88-726). Two trials of blood glucose reduction as primary prevention failed to show a significant difference in aggregate cardiac events. The individual cardiac outcomes (cardiovascular mortality and MI each alone) showed results consistent with the aggregate outcomes.

ABSTRACT

BACKGROUND: Type 2 diabetes is increasingly recognized as a powerful risk factor for coronary artery disease (CAD) events. In its recommendations for treating cholesterol levels, the Third Adult Treatment Panel of the National Cholesterol Education Program (NCEP) considers diabetes mellitus the equivalent of preexisting CAD.¹ The United Kingdom Prospective Diabetes Study (UKPDS) showed that blood pressure control had a greater overall effect on diabetes-related morbidity and mortality than did intensive glucose control.² The study under consideration examines data from the major trials of cardiovascular risk reduction to determine the relative benefit of controlling blood pressure and cholesterol and glucose levels in patients with type 2 diabetes.

POPULATION STUDIED: Adult patients with diabetes who participated in a variety of studies looking at reduction of risk factors for CAD.

STUDY DESIGN AND VALIDITY: This meta-analysis combined data from previous studies of intensive coronary risk factor reduction in patients with diabetes. The authors searched MEDLINE from 1966 to 2001 for articles published on the topic in English. Studies were included if they were randomized controlled trials of adults that included some patients with diabetes, compared intensive risk factor reduction with drug therapy versus either placebo or routine care, had at least 1 year of follow-up, and reported the requisite cardiovascular outcomes. The studies were independently reviewed by 2 authors for inclusion in the analysis based on these inclusion criteria; disagreement was resolved by consensus. There was no explicit validity assessment of the articles. Data were abstracted in a structured manner. The results were analyzed for heterogeneity and pooled appropriately.

OUTCOMES MEASURED: The outcomes measured included “aggregate cardiac events” (CAD death and nonfatal myocardial infarction [MI]), cardiovascular mortality, MI, and stroke. The results are presented in changes in rates over person-years and as person-years needed to treat. This was done to account for the variable lengths of patient follow-up in these large trials; these findings can be interpreted similarly to standard event rates and numbers needed to treat (NNT). One caveat is that to report an outcome for cholesterol lowering and blood pressure control across a time span of only 1 person-year is artificial, given that most changes in outcomes produced by these therapies take several years to manifest themselves.

RESULTS: Cholesterol lowering (a total of 5 studies of both primary and secondary prevention) reduced aggregate cardiac events (30 vs 41 events per 1000 person-years, NNT for 1 year 106, 95% confidence interval [CI} 62-366). Cholesterol lowering as secondary prevention contributed most to this result (3 trials, 34 vs 44 events per 1000 person-years, NNT for 1 year 120, 95% CI, 61-4856); the results of primary prevention through cholesterol lowering did not reach statistical significance. Blood pressure reduction also reduced aggregate cardiac events (17 vs 23 per 1000 person-years, NNT for 1 year 157, 95% CI, 88-726). Two trials of blood glucose reduction as primary prevention failed to show a significant difference in aggregate cardiac events. The individual cardiac outcomes (cardiovascular mortality and MI each alone) showed results consistent with the aggregate outcomes.