Abstract

Type 2 diabetes (DM) increases the risk of coronary heart disease (CHD) by a factor of 2 to 4. In the Scandinavian Simvastatin Survival Study, 483 of the enrolled 4444 patients with CHD also had type 2 DM. Simvastatin (20-40 mg/day) decreased low density lipoprotein (LDL) cholesterol by 35% and triglycerides by 15% while raising high density lipoprotein (HDL) cholesterol by 8%. In the patients with DM, over 5.4 years, simvastatin significantly reduced the number of major coronary events, revascularizations and coronary mortality. Pravastatin also reduces the risk of coronary events in diabetic patients with coronary syndromes, and atorvastatin reduced cardiac events in patients with type 2 DM and dyslipidemia. CARDS (Collaborative Atorvastatin Diabetes Study) was the first study of a statin set up solely in patients with DM. In CARDS, the 2838 enrolled patients with type 2 DM had no documented previous history of CHD but did have one of retinopathy, albuminuria, current smoking or hypertension. In CARDS, atorvastatin (10 mg daily) lowered LDL-cholesterol levels by 34% and triglycerides by 18%, but had no effect on HDL-cholesterol. Associated with these changes, after a follow-up of nearly 4 years, less patients in the atorvastatin group (83 of 1428 patients) had had a major cardiovascular event than in the placebo group (127 of 1410 patients). After 4 years, there were reductions with atorvastatin in acute coronary heart disease events (50 vs. 74), coronary revascularizations (12 vs. 18) and stroke (21 vs. 35). Recently, evidence has shown that better outcomes can be achieved with intensive lipid lowering (atorvastatin 80 mg) than with moderate lipid lowering (pravastatin 40 mg) in patients hospitalized for an acute coronary syndrome. In the 734 patients with DM, the composite primary endpoint (death, myocardial infarction, unstable angina requiring rehospitalization, revascularization and stroke) occurred in 34.6% of patients treated with pravastatin compared to 28.8% of patients treated with atorvastatin. DM is commonly associated with low HDL cholesterol and high triglyceride levels. This dyslipidemia can be reversed by fibrates or nicotinic acid. The Veterans Affairs Cooperative Studies Program High-Density Lipoprotein Cholesterol Intervention Trial (VA-HIT) was the first large clinical trial to show that a fibrate reduced the risk of major cardiovascular events in diabetic men with established CHD and low HDL cholesterol. In VA-HIT, 769 patients had DM, and 1425 had normal fasting glucose. Gemfibrozil caused a lesser increase in HDL cholesterol in diabetic (5%) than in normal subjects (8%) and also caused a lesser decrease in triglycerides in diabetic (20%) than in normal subjects (29%). Despite this, gemfibrozil had a greater ability to reduce the primary combined end point in the diabetic (32% risk reduction) than in those without DM (18%); this was due to a greater reduction for death from CHD and stroke in the patients with type 2 DM. Fenofibrate reduces the angiographic progression of coronary artery disease. Nicotinic acid is a possible alternative to fibrates in patients who do not tolerate fibrates but has the disadvantage of reducing glucose control. Obesity is associated with insulin resistance and is a major risk factor for type 2 DM. Agents that inhibit cholesterol absorption (orlistat, ezetimibe, plant sterols) have small beneficial effects on lipids in patients with type 2 DM, but it is not known whether this translates into a reduction in CHD.

Keywords: Atorvastatin, bezafibrate, coronary artery disease, ezetimibe, fenofibrate, fluvastatin, gemfibrozil, nicotinic acid, orlistat, plant sterols