Do Persons with Diabetes Benefit from Combination Statin and Fibrate Therapy?

作者：Rosenblit Paul D^*

来源：Current Cardiology Reports, 2012, 14(1).

DOI：10.1007/s11886-011-0237-7

• Atherosclerosis
• Atherogenic dyslipidemia
• Atherogenic lipoprotein phenotype
• Bezafibrate
• Cardiovascular disease, Chylomicron remnants Combination therapies, Diabetes
• Diabetic dyslipidemia
• Dyslipidemia
• Dyslipidemia of insulin resistance
• Fenofibrate
• Fibrates
• Gemfibrozil
• HDL-C
• Hypertriglyceridemia
• Lipid-modifying therapies, Macrovascular/microvascular disease
• Residual risk reduction
• Statin-fibrate combination
• Triglyceride-rich lipoproteins
• Triglycerides
• T2DM

Combination fibrate-statin therapy favorably modifies the atherogenic, triglyceride-rich lipoprotein environment, common to insulin resistance, diabetes, and higher cardiovascular disease (CVD) risk. Five major fibrate randomized clinical trial (RCT) results (HHS, VA-HIT, BIP, FIELD, and ACCORD-Lipid) demonstrated four consistent features: 1) the highest CVD event rates occurred in the placebo subgroups possessing atherogenic "moderate" dyslipidemia (triglycerides, >200 mg/dL, and low high-density lipoprotein cholesterol [HDL-C], <35-40 mg/dL); 2) with this subgroup having the greatest "hypothesis-generating" fibrate benefit (27% to 65% relative risk reduction, variable significance [P values ranging 0.057-0.005]); 3) those subgroups without moderate dyslipidemia had relatively lower CVD event rates; and 4) little or no benefit from fibrates. The ACCORD-Lipid results, specifically, demonstrated benefits against the background of statin therapy. Three independent meta-analyses combining the five RCTs, which provided a large sample of moderate dyslipidemia participants (i.e., 2401 on fibrates; 2270 on placebo), demonstrated a fibrate benefit with significant heterogeneity of effect across lipid subgroups (P=0.0002). The fibrate benefit was observed in " low HDL-C only" patients, reducing CVD events by 17% (P<0.001) or " hypertriglyceridemia-only" patients, reducing CVD events by 28% (P<0.001), or " atherogenic (moderate) dyslipidemia" phenotype, reducing CVD events by 30% (P<0.0001), compared with a nonsignificant 6% reduction (P=0.13) in nonatherogenic dyslipidemia patients. Fibrate RCTs in patients with diabetes (FIELD and ACCORD-Lipid) also demonstrated significant microvascular (ie, retinopathy and nephropathy) outcome benefit possibly independent of lipid levels.

• 出版日期2012-2