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Do persons with diabetes benefit from combination statin and fibrate therapy
Current Cardiology Reports, 01/05/2012
Clinical Article
Rosenblit PD – Fibrate randomized clinical trials (RCTs) in patients with diabetes (FIELD and ACCORD–Lipid) also demonstrated significant microvascular (ie, retinopathy and nephropathy) outcome benefit possibly independent of lipid levels.
Methods- 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:
- 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);
- 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]);
- Those subgroups without moderate dyslipidemia had relatively lower CVD event rates;
- And 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.