Treating the Common Dyslipidemia in Patients with Type 2 Diabetes: Insights from FIELD on the Effects of Fenofibrate on CVD Risk

Sergio Fazio
US Endocrinology, 2006;(1):52-58
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Current Indications for Statin and Fibrate Therapy

The evidence of cardiovascular protection afforded by statins has recently extended beyond patients with hypercholesterolemia.With the publication of several trials,1-7 bold extrapolations of the power of statin therapy in cardiovascular prevention have been offered:

  1. Statins equally reduce risk in subjects with or without hypercholesterolemia
  2. Statins may be the first choice in patients with diabetes; and
  3. The guideline goal for LDL-cholesterol may need to be lowered to 70mg/dL. Thus, it seems that statin therapy may become necessary in high-risk individuals, even in the absence of dyslipidemia and possibly even when LDL-cholesterol levels are <100mg/dL. However, it should be emphasized that the optional goal of LDL-cholesterol levels <70mg/dL applies only to individuals who are very high-risk (i.e. established CVD plus multiple major risk factors), as there are potential side effects of using high statin doses to reduce LDL-cholesterol to very low levels.8


Similar momentum has been building for fibrates. These agents were originally indicated for patients with severely high triglyceride levels. However, the benefit of fibrates has recently been extended to treat the atherogenic dyslipidemia that afflicts most patients with type 2 diabetes, which is characterized by high levels of triglycerides, LDL particles that are small and dense, and low levels of HDL-cholesterol.9-11 The FIELD study, discussed in detail below, provides important data regarding the potential for fenofibrate to reduce cardiovascular risk in patients with type 2 diabetes both with and without dyslipidemia.

Treatment of Atherogenic Dyslipidemia to Reduce Cardiovascular Risk

The current guidelines of the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III)10 and the American Diabetes Association (ADA)12 highlight the importance of LDL-cholesterol reduction in high risk patients, but at the same time encourage physicians to position all patients with type 2 diabetes and insulin resistance in the high cardiovascular risk category. Because patients with type 2 diabetes and insulin resistance are commonly affected by the atherogenic dyslipidemia, characterized by high triglycerides and low HDL-cholesterol, one could argue that the optimal lipid intervention in these patients should be one targeting these abnormalities. Triglyceride and HDL-cholesterol levels have been shown to predict coronary event rates independently from LDL-cholesterol levels in populations from Europe and the US.13-15 The knowledge that the ratio of total cholesterol to HDL-cholesterol is the most sensitive index of cardiovascular disease progression highlights the important contribution of atherogenic dyslipidemia to cardiovascular risk, given that this ratio is mostly determined by abnormalities of triglyceride metabolism.

References:
  1. Heart Protection Study Collaborative Group, “MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial”, Lancet (2002);360: pp. 7–22
  2. Sever P S, Dahlof B, Poulter N R et al.,“Prevention of coronary and stroke events with atorvastatin in hypertensive patients who have average or lower-than-average cholesterol concentrations, in the Anglo-Scandinavian Cardiac Outcomes Trial – Lipid Lowering Arm (ASCOT-LLA): a multicentre randomised controlled trial”, Lancet (2003);361: pp. 1,149–1,158.
  3. Colhoun H M, Betteridge D J, Durrington P N et al.,“Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): multicentre randomised placebo-controlled trial”, Lancet (2004);364: pp. 685–696.
  4. Rader D J, Davidson M H, Caplan R J, Pears J S,“Lipid and apolipoprotein ratios: association with coronary artery disease and effects of rosuvastatin compared with atorvastatin, pravastatin, and simvastatin”, Am J Cardiol (2003);91: pp. 20C-23C; discussion 23C–24C.
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  25. Jones P H, Davidson M H,“Reporting rate of rhabdomyolysis with fenofibrate + statin versus gemfibrozil + any statin”, Am J Cardiol (2005);95(1): pp. 120–122.
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