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EXPEDITED REVIEW

The Reduction of Inflammatory Biomarkers by Statin, Fibrate, and Combination Therapy Among Diabetic Patients With Mixed Dyslipidemia

The DIACOR (Diabetes and Combined Lipid Therapy Regimen) Study

Joseph B. Muhlestein, MD, FACC^_*,,_*, Heidi T. May, MSPH^_*, Jonathan R. Jensen, BS^_*, Benjamin D. Horne, PhD, MPH^_*, Richard B. Lanman, MD, Farangis Lavasani, FNP^_*, Robert L. Wolfert, PhD, Robert R. Pearson, BS^_*, H. Daniel Yannicelli, MD and Jeffrey L. Anderson, MD, FACC^_*,

^_* Cardiovascular Department, LDS Hospital, Salt Lake City, Utah
Cardiology Division, University of Utah, Salt Lake City, Utah
diaDexus Inc., San Francisco, California
Abbott Laboratories, Abbott Park, Illinois

Manuscript received February 2, 2006; revised manuscript received April 20, 2006, accepted April 23, 2006.

^_* Reprint requests and correspondence: Dr. J. Brent Muhlestein, LDS Hospital Cardiovascular Department, 8th Avenue and C Street, Salt Lake City, Utah 84143. (Email: brent.muhlestein{at}intermountainmail.org).

OBJECTIVES: The primary objective was to determine the effect of statin-fibrate combination therapy on inflammatory biomarkers in patients with diabetes.

BACKGROUND: Atherosclerosis is a long-term, chronic inflammatory disease that is exacerbated in patients with diabetes.

METHODS: Patients (n = 300) with type II diabetes, mixed dyslipidemia (2 or more of low-density lipoprotein 100 mg/dl, triglycerides 200 mg/dl, or high-density lipoprotein <40 mg/dl), and no history of coronary heart disease were randomly assigned to receive simvastatin 20 mg, fenofibrate 160 mg, or a combination of simvastatin 20 mg and fenofibrate 160 mg daily. At 12 weeks after randomization, we measured levels of high-sensitivity C-reactive protein (hsCRP) and lipoprotein-associated phospholipase A₂ (Lp-PLA₂).

RESULTS: At 12 weeks, median hsCRP was significantly reduced (–14.6%, p = 0.004) from baseline, but the effect did not differ between treatments. The effect was greatest among patients with baseline hsCRP levels >2.0 mg/l (fenofibrate = –18.9%, p = 0.002 vs. baseline; simvastatin = –24.8%, p < 0.0001; combination = –27.3%, p = 0.002). Likewise, median Lp-PLA₂ levels in the overall study population were significantly reduced (–16.8%, p < 0.0001), and the effect did not differ among treatments. This effect also was greatest among patients with increased baseline levels of Lp-PLA₂ greater than the median of 320.9 ng/ml (fenofibrate = –41.3%, p < 0.0001; simvastatin = –47.5%, p < 0.0001; combination = –46.8%, p < 0.0001).

CONCLUSIONS: Simvastatin, fenofibrate, and combination therapy each lowered hsCRP and Lp-PLA₂. These anti-inflammatory effects were most pronounced among patients with increased baseline levels. Combination therapy was no more effective than either form of monotherapy. (The DIACOR Study; http://www.clinicaltrials.gov/ct/show/NCT00309712?order=1)

Abbreviations and Acronyms   CRP = C-reactive protein   HDL-C = high-density lipoprotein cholesterol   hsCRP = high-sensitivity C-reactive protein   LDL-C = low-density lipoprotein cholesterol   Lp-PLA2 = lipoprotein-associated phospholipase A2

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