Do persons with diabetes benefit from combination statin and fibrate therapy?
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.
Diabetes/Lipid Management & Research Center, 18821 Delaware Street, Suite 202, Huntington Beach, CA 92648, USA. rosenblitpd@pol.net
Paul D
PD
Rosenblit
D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy*; D003925:Diabetic Angiopathies / Q000188:drug therapy / Q000517:prevention & control*; D004359:Drug Therapy, Combination; D050171:Dyslipidemias / Q000188:drug therapy*; D005260:Female; D011345:Fenofibrate / Q000627:therapeutic use; D058607:Fibric Acids / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D000960:Hypolipidemic Agents / Q000627:therapeutic use*; D007333:Insulin Resistance; D008297:Male; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors; D016896:Treatment Outcome
D058607:Fibric Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000960:Hypolipidemic Agents; D011345:Fenofibrate