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Am Fam Physician. 2005;71(3):588-592

Type 2 diabetes mellitus is increasing in prevalence and is a common cause of morbidity and mortality. In persons with diabetes, vascular complications are the usual cause of adverse outcomes, and the latter often are divided into macrovascular (i.e., coronary artery disease, cerebrovascular disease, and peripheral vascular disease) and microvascular (i.e., retinopathy, nephropathy, and neuropathy). Tight glucose control reduces microvascular complications but does not affect macrovascular changes. Controlling cardiovascular risk factors in persons with diabetes can reduce macrovascular complications, and guidelines for the management of hypercholesterolemia in patients with type 2 diabetes have been formulated by the American College of Physicians (ACP).

Snow and colleagues in the Clinical Efficacy Assessment Subcommittee of the ACP developed guidelines for hyperlipidemia management in type 2 diabetes based on a systematic review of the evidence performed by Vijan and colleagues. Because there are no studies of lipid control specifically in this patient population, subgroup analyses were used, looking only at patients with diabetes who were part of larger studies. Lipid management values in primary and secondary prevention were reviewed.

Six large primary prevention studies looking at lipid control (with various drugs) and its effect on cardiovascular disease were included, as were eight trials reporting secondary prevention in patients with diabetes. After conducting a meta-analysis for the trial results of the diabetes subgroup, primary prevention treatment demonstrated a pooled relative risk—with lipid-lowering treatment—of 0.78 (confidence interval [CI], 0.67 to 0.89) and a pooled absolute risk reduction of 0.03 (CI, 0.01 to 0.04). The number needed to treat to prevent one cardiovascular event was 34.5, for a weighted trial average of 4.3 years.

In the secondary trial studies, lipid-lowering treatment had a pooled relative risk reduction similar to that in the primary prevention analyses, but because the pooled absolute risk was higher in this group, the number needed to treat was only 13.8, for a weighted trial average of 4.9 years. Statins were found to be safe, with minimal or no significant increase in liver function test abnormalities or elevation of creatine kinase levels. Rhabdomyolysis did not occur in any study participant, and myalgias were not more common than among the control populations. Liver enzyme monitoring is probably necessary only in patients with symptoms or elevated liver enzyme levels at baseline, or in those taking drugs that interact with statins to increase the risk for adverse events.

The authors conclude that because patients with type 2 diabetes are at higher risk for adverse cardiovascular events, aggressive risk management is appropriate. Lipid lowering can reduce major cardiovascular event risk by 22 to 24 percent. Statins appear to be the best agent for this purpose, and Vijan and colleagues recommend the use of statins in patients at average or above-average risk for cardiovascular disease. However, the target low-density lipoprotein (LDL) cholesterol level that requires treatment is uncertain, and the absolute risk reduction is much lower among persons without evidence of cardiovascular disease. Based on this analysis, the ACP has made the recommendations listed inthe accompanying table, noting that these are clinical practice guidelines and are not intended to override physician judgment.

Lipid-lowering therapy should be used for secondary prevention in all patients with type 2 diabetes and coronary artery disease.
Lipid-lowering therapy should be used for primary prevention against macrovascular complications in persons with type 2 diabetes who have any other cardiovascular risk factors (i.e., older than 55 years, hypertension, smoking, left ventricular hypertrophy, previous cerebrovascular or peripheral arterial disease).
Statins appear to be the drug of choice, and at least moderate doses should be used (atorvastatin, 20 mg per day; lovastatin, 40 mg per day; pravastatin, 40 mg per day; or simvastatin, 40 mg per day). The potential benefit of treatment to a specific target low-density lipoprotein cholesterol level remains unclear.
In patients taking statins, routine liver function tests or muscle enzyme monitoring is unnecessary unless there is a specific reason.

editor's note: The Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults, completed in 2001, set criteria for primary and secondary prevention of coronary heart disease (CHD) by improving lipid profiles in patients at risk for CHD.1 This report focused on patients with a relatively high risk for CHD and noted the benefit of more intensive LDL-lowering treatment. Elevated LDL cholesterol levels remain the primary target, although low high-density lipoprotein (HDL)-cholesterol levels also are recognized as an important risk factor. CHD equivalents include evidence of atherosclerotic disease, diabetes, and multiple risk factors that confer a 10-year risk for CHD. The LDL cholesterol goal for persons with CHD or CHD equivalents is less than 100 mg per dL (2.60 mmol per L). Most patients need to take LDL cholesterol-lowering drugs to achieve this goal. Some authorities recommend initiating drug therapy in the hospital in patients admitted for a CHD-related illness if they have a cholesterol level higher than 100 mg per dL. This step helps motivate patients to continue taking the medication and increases long-term compliance. Patients with metabolic syndrome also require weight control, increased physical activity, and treatment of elevated triglycerides and low HDL cholesterol levels. Interventions that improve adherence to lipid-lowering medications include simplifying the medical regimen, providing explicit patient instructions, rewarding adherence, and encouraging the support of family and friends.1 The fourth report from the NCEP is being discussed, and many experts are supporting further reductions in LDL cholesterol levels, to 60 to 80 mg per dL (1.55 to 2.05 mmol per L) to reduce CHD risk in high-risk patients.2 —r.s.

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Copyright © 2005 by the American Academy of Family Physicians.

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