What is the relative cardiovascular benefit of lowering cholesterol, blood pressure, and glucose levels in patients with type 2 diabetes? - Patient-Oriented Evidence that Matters

Journal of Family Practice, April, 2002 by John Epling

Huang ES, Meigs JB, Singer DE. The effect of interventions to prevent cardiovascular disease in patients with type 2 diabetes mellitus. Am J Med 2001; 111:633-42.

* 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.

While the process of conducting the meta-analysis of results was appropriate, it falls short of the ideal of a systematic review because of the lack of a serious attempt to find all existing data on the subject (eg, through searches of other databases and unpublished studies) and because of the lack of validity assessment of the included studies. These are not fatal flaws, as it is not likely that the authors missed any important studies, and the articles included are generally large, well-performed randomized controlled trials.

* 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 rotes 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 rotes 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 must 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.

RECOMMENDATIONS FOR CLINICAL PRACTICE

This study reinforces the conclusions of the UKPDS study and the recommendations of the NCEP guidelines that aggressive management of cholesterol and blood pressure in patients with diabetes ks essential in preventing CAD. Intensive control of blood sugar levels does not seem to alter CAD events or mortality.

REFERENCES

(1.) Third report of the National Cholesterol Education Program Expert Panel on detection, evaluation and treatment of high blood cholesterol in adults. Bethesda. Md: US Dept of Health and Human Services, Public Health Service, National Institutes of Health, National Heart, Lung, and Blood Institute; 2001.

(2.) UK prospective Diabetes Study Group. Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. BMJ 1998; 317:703-13.

John Epling, MD
Center for Evidence-Based Practice
SUNY-Upstate Medical University
Syracuse, New York
E-mail: Eplingj@upstate.edu