Should you put all diabetic patients on statins? Aggressive statin therapy achieves greater cardiovascular benefit, regardless of baseline LDL, than just "treating to goal"

Journal of Family Practice, April, 2007 by Lawrence A. Leiter

Practice recommendations

* Statins are the therapy of choice for lowering LDL cholesterol in patients with diabetes (A).

* All diabetes patients over the age of 40 should receive statin therapy, regardless of baseline LDL cholesterol (A).

* Diabetes patients experience greater cardiovascular benefit from aggressive lipid-lowering therapy than from more moderate lipid-lowering therapy (B).

Strength of recommendation (SOR)

A Good quality patient-oriented evidence

B Inconsistent or limited-quality patient-oriented evidence

C Consensus, usual practice, opinion, disease-oriented evidence, case series

Dyslipidemia in patients with diabetes is underdiagnosed and undertreated, and diabetes patients not receiving statin therapy are at high risk for cardiovascular disease. Clinical trial data show that we should consider statins for all adults with diabetes, irrespective of cardiovascular disease status or baseline low-density lipoprotein (LDL) cholesterol levels. Furthermore, aggressive statin therapy is more beneficial than moderate treatment. Patients with diabetes typically have elevated triglycerides and low high-density lipoprotein (HDL) cholesterol levels, but their LDL cholesterol levels are similar to those in the general population. (1) Nevertheless, emerging evidence shows that patients with diabetes may benefit from statins even in the absence of elevated LDL. (2-4) Though various agents can reduce LDL cholesterol, the most impressive cardiovascular outcomes are associated with statins. (4-10)

* We're undertreating

Despite overwhelming evidence supporting use of statins for lipid-lowering, management of cholesterol levels is inadequate in clinical practice, (11,12) Furthermore, data from US medical records suggest that lipid management in diabetes patients is particularly poor. (13) In the decade between National Health and Nutrition Examination Surveys I and II, coronary heart disease (CHD) mortality declined significantly among patients without diabetes (44% in men, 30% in women) but far less so among patients with diabetes. (14) International treatment guidelines such as those of the American Diabetes Association (ADA), (15) National Cholesterol Education Program Third Adult Treatment Panel (NCEP ATP III), (16,17) and the Joint European Societies[TM] classify diabetes as a CHD risk equivalent and, accordingly, have established stringent lipid goals for diabetes patients.

Stringent lipid goals

The first priority is to reduce LDL cholesterol to <100 mg/dL (2.6 mmol/L), as advocated by all 3 guidelines.

* For patients with diabetes and established cardiovascular disease, the recent ATP III guideline update and the ADA recommendations suggest the option of lowering LDL cholesterol even further, to <70 mg/dL (1.8 mmol/L). (17)

* Immediate initiation of statin therapy, in addition to dietary and lifestyle changes, is also generally recommended regardless of baseline LDL cholesterol levels in all patients with diabetes and established cardiovascular disease. (15,17)

* It is also recommended for most diabetes patients without clinically evident cardiovascular disease (15) or LDL cholesterol [greater than or equal to] 130 mg/dL (2.6 mmol/L). (17)

Undertreatment of hypercholesterolemia may be more widespread in patients with diabetes than in those without diabetes (FIGURE). (19-21) Outpatient medical data from 47,813 patients with coronary heart disease revealed that patients with diabetes were: 26% less likely to have their lipid profile assessed than patients without diabetes, and 17% less likely to receive a lipid-lowering medication. (13) The AUDIT survey (Analysis and Understanding of Diabetes and Dyslipidemia: Improving Treatment) (22) of physicians who specialized in the management of diabetes revealed that:

* Most ([greater than or equal to] 90%) routinely assess total cholesterol, LDL and HDL cholesterol, or triglycerides.

* Only 20% believe that at least 80% of patients achieve LDL cholesterol goals.

* They were more likely to set less stringent LDL goals for diabetes patients without cardiovascular disease than for those with cardiovascular disease.

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* Lipid-lowering treatments

Statins are the therapy of choice for lowering LDL cholesterol levels (including small, dense LDL), (15,17,18) and they also reduce triglycerides and modestly elevate HDL cholesterol. Statins generally are well tolerated with few side effects. (23,24) Myopathy is the most serious adverse event, but it curs only rarely. Unlike other lipid-lowering therapies, statins boast a wealth of data from large, randomized, placebo-controlled trials conclusively demonstrating significant reduction in both primary and secondary cardiovascular risk. (5-10,25-28) Because of efficacy and safety, they are the first-line option.

Other pharmacologic options include

bile acid sequestrants, ezetimibe, fibrates, and niacin (TABLE 1). (29-32)

Bile acid sequestrants modestly reduce LDL and slightly increase HDL cholesterol, and have no effect or even mildly increase triglycerides, which are often elevated in patients with diabetes. Side effects (constipation, gastrointestinal distress) have limited their use.