Evidence:

• Several randomized controlled trials of both primary and secondary prevention of CVD have shown that HMG-CoA inhibitors (statins) (108; 109; 110; 111; 112; 113; 114) and fibric acid derivatives (fibrates) (115; 116; 117; 118; 119) lower the risk of cardiovascular events by about 25% to 30% in persons both with and without diabetes.
• A secondary analysis of two secondary prevention statin treatment studies found that only diabetes patients, and not those without diabetes, with LDL cholesterol levels <124 mg/dL (3.2 mmol/L) benefited from treatment (120).
• The MRC/BHF Heart Protection Study, a large trial of persons with CVD or at high risk for CVD, including 5963 patients with diabetes (both with and without previous CVD), found that treatment with simvastatin was associated with a significant decrease in cardiovascular deaths and overall mortality after 5 years (RR, 0.83 [CI, 0.75 to 0.91]) (113).
• A subgroup analysis of the diabetes patients in the MRC/BHF Heart Protection Study found that the cardiovascular mortality risk reduction with simvastatin was about 25, regardless of age, sex, or treatment for hypertension, and that the risk reduction remained significant even for those with LDL cholesterol levels <115.8 mg/dL (3.0 mmol/L). Furthermore, major cardiovascular events were reduced by 30% (NNT, 32; P = 0.05) even among the 1343 diabetes patients without known CVD whose LDL cholesterol was <115.8 mg/dL (3.0 mmol/L) at baseline (121).
• Subgroup analyses of two recent studies have found no benefit of statins in patients with diabetes. The lipid-lowering arm of ALLHAT (ALLHAT-LLT), which included 3600 subjects with type 2 diabetes, did not find a benefit of pravastatin treatment vs. usual care on mortality or CV-event rates in those both with and without diabetes. The surprising lack of statin benefit in this trial is thought to be mainly due to the high use of nonstudy statin therapy in the usual-care group (122). The lipid-lowering arm of ASCOT (ASCOT-LLA), an ongoing antihypertensive trial of almost 20,000 hypertensive patients, stopped their lipid-lowering arm after 1 year when they found that atorvastatin treatment in persons with normal cholesterol levels was associated with a 36% reduction in cardiovascular events. This benefit was not seen in the subgroup of diabetes patients; however, the event rate in that group may have been too low to detect a benefit after only 1 year (123).

Comments:

• Persons with diabetes have a two to three times higher baseline risk of CVD and may therefore derive even greater absolute benefit with lipid-lowering therapy than those without diabetes. The LDL cholesterol target recommended for persons with diabetes is <100 mg/dL (5.6 mmol/L).