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

  • Diabetes and Cardiovascular Disease (ND Wong, Section Editor)
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Abstract

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.

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Abbreviations

A to Z:

Aggrastat-to-Zocor Trial

ACCORD-Lipid:

Action to Control Cardiovascular Risk in Diabetes

BECAIT:

Bezafibrate Coronary Atherosclerosis Intervention Trial

BIP:

Bezafibrate Infarction Prevention

CTT:

Cholesterol Treatment Trialists

DAIS:

Diabetes Atherosclerosis Intervention Study

FIELD:

Fenofibrate Intervention and Event Lowering in Diabetes

FIELD CIMT:

Fenofibrate Intervention and Event Lowering in Diabetes-Carotid Intima-Media Thickness

HHS:

Helsinki Heart Study

IDEAL:

Incremental Decrease in End Points Through Aggressive Lipid Lowering

NCEP-ATP:

National Cholesterol Education Program Adult Treatment Panel III

PROVE-IT-TIMI 22:

Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction 22

SAFARI:

Effectiveness and Tolerability of Simvastatin Plus Fenofibrate for Combined Hyperlipidemia

SENDCAP:

St. Mary’s, Ealing, Northwick Park Diabetes Cardiovascular Prevention

TNT:

Treating to New Targets

VA-HIT:

Veterans Affairs High-Density Lipoprotein Intervention Trial

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Disclosure

Conflicts of interest: P.D. Rosenblit: has received honoraria for Advisory Board-Consulting from Eli Lilly; research funding at his clinical trial site from AstraZeneca, Dexcom, EISAI, GlaxoSmithKline. Lifescan division of Johnson & Johnson, Merck, Novo Nordisk, Novartis, Pfizer, Roche, Sanofi, Takeda, and Tolerx; and honoraria for speaking from Abbott, Amylin, Boehringer-Ingelheim, Bristol-Meyers Squibb, Lilly, GlaxoSmithKline, Kowa, Merck, NovoNordisk, and Sanofi.

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    Paul D. Rosenblit

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Rosenblit, P.D. Do Persons with Diabetes Benefit from Combination Statin and Fibrate Therapy?. Curr Cardiol Rep 14, 112–124 (2012). https://doi.org/10.1007/s11886-011-0237-7

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