Cardiovascular disease with diabetes or the metabolic syndrome: should statins or fibrates be first line lipid therapy?
OBJECTIVE
Subgroups with diabetes or with features of the metabolic syndrome have been increasingly highlighted in large clinical endpoint trials with lipid therapy. This review will focus on the results of trials with statins or fibrates and examine the strength of the evidence for major cardiovascular event reduction with each kind of therapy in these high-risk subgroups that typically have low-to-moderate levels of LDL cholesterol.


RESULTS
Of six statin trials in populations with moderately increased LDL cholesterol only one, the Heart Protection Study, has shown that statin therapy will significantly reduce the major coronary heart disease events of non-fatal myocardial infarction or coronary heart disease death in diabetes. None of these trials has shown that statins have a particular predilection for reducing cardiovascular events in individuals with higher levels of body weight or other features of the metabolic syndrome. There are far fewer trial data with fibrates than with statins. However, the Veterans Affairs High Density Lipoprotein Intervention Trial has shown that a fibrate can significantly reduce major cardiovascular events, most particularly coronary heart disease death, in those with diabetes as well as those without diabetes who have insulin resistance. Indeed, all fibrate trials show that this therapy appears to selectively benefit the individual with obesity and features of the metabolic syndrome.


CONCLUSIONS
Based principally on evidence from the Veterans Affairs High Density Lipoprotein Intervention Trial and the cumulative experience with statins, trial data would thus far suggest that the patient with a modest increase in LDL cholesterol who has diabetes or features of the metabolic syndrome might be likely to achieve more substantial cardiovascular benefit from fibrate than from statin therapy.
Robins
Sander J
SJ
Division of Endocrinology, Nutrition, and Diabetes, Boston University School of Medicine, Evans 201, 88 East Newton Street, Boston, MA 02118, USA. sjrobins@bu.edu
D000924:Anticholesteremic Agents / Q000627:therapeutic use; D015992:Body Mass Index; D002097:C-Reactive Protein / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000150:complications / Q000188:drug therapy*; D002784:Cholesterol / Q000097:blood; D002995:Clofibric Acid / Q000627:therapeutic use*; D048909:Diabetes Complications; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D000960:Hypolipidemic Agents / Q000627:therapeutic use; D007333:Insulin Resistance; D008074:Lipoproteins / Q000097:blood; D024821:Metabolic Syndrome / Q000150:complications*; D009203:Myocardial Infarction / Q000188:drug therapy; D020521:Stroke / Q000188:drug therapy; D016896:Treatment Outcome
D000924:Anticholesteremic Agents; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000960:Hypolipidemic Agents; D008074:Lipoproteins; D002995:Clofibric Acid; D002097:C-Reactive Protein; D002784:Cholesterol