Clinical Studies
The effect of interventions to prevent cardiovascular disease in patients with type 2 diabetes mellitus

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Abstract

Purpose

Cardiovascular complications account for over 50% of mortality among patients with type 2 diabetes mellitus. We quantify the cardiovascular benefit of lowering cholesterol, blood pressure, and glucose levels in these patients.

Methods

We conducted a meta-analysis of randomized controlled trials in type 2 diabetes or diabetes subgroups, comparing the cardiovascular effects of intensive medication control of risk factor levels in standard therapy or placebo. We identified trials by searching MEDLINE (1966 to 2000) and review articles. Treatment details, patient characteristics, and outcome events were obtained using a specified protocol. Data were pooled using fixed-effects models.

Results

Seven serum cholesterol-lowering trials, six blood pressure–lowering trials, and five blood glucose-lowering trials met eligibility criteria. For aggregate cardiac events (coronary heart disease death and nonfatal myocardial infarction), cholesterol lowering [rate ratio (RR) = 0.75; 95% confidence interval (CI): 0.61 to 0.93) and blood pressure lowering (RR = 0.73; 95% CI: 0.57 to 0.94) produced large, significant effects, whereas intensive glucose lowering reduced events without reaching statistical significance (RR = 0.87; 95% CI: 0.74 to 1.01). We observed this pattern for all individual cardiovascular outcomes. For cholesterol-lowering and blood pressure–lowering therapy, 69 to 300 person-years of treatment were needed to prevent one cardiovascular event.

Conclusions

The evidence from these clinical trials demonstrates that lipid and blood pressure lowering in patients with type 2 diabetes is associated with substantial cardiovascular benefits. Intensive glucose lowering is essential for the prevention of microvascular disease, but improvements in cholesterol and blood pressure levels are central to reducing cardiovascular disease in these patients.

Section snippets

Study selection

From a MEDLINE database (1966 to 2000), we identified randomized controlled trials, published in English, involving adults with type 2 diabetes. Diabetic patients were either the focus of studies or subgroups of larger trials. We used specific terms to identify trials of cholesterol-lowering, blood pressure–lowering, and glucose-lowering therapies. Search details are available upon request. We supplemented the search with an examination of reference lists from initially identified trials and

Study and patient characteristics

In all lipid-lowering trials, diabetic patients were a small subset of the study population (Table 1). Baseline cholesterol levels varied, ranging from LDL cholesterol 135 mg/dL or lower in the Cholesterol and Recurrent Events Trial (CARE) (5) and the Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial (VA-HIT) (26) to higher than 200 mg/dL in the Helsinki Heart Study (21). In the Helsinki Heart Study, Air Force/Texas Coronary Arteriosclerosis Prevention Study

Discussion

In our analysis of diabetic subpopulations in lipid-lowering trials, the point estimates for all outcomes indicated large reductions in cardiovascular events. These effects were statistically significant for aggregate cardiac events and myocardial infarction. The benefits of antihypertensive agents were large and significant across all outcomes and for the majority of substudy analyses. In contrast, glucose lowering had a marginally significant effect on cardiovascular outcomes. Of note, the

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  • Cited by (0)

    This study was supported by Public Health National Research Service Award PE-11001; the American Diabetes Association; SmithKline Beecham, Research Triangle Park, North Carolina; and Health Resources and Service Administration Award 2D08-PE-50018.

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