Novel HDL-Targeted Therapies -- The Search Continues

Linda Brookes, MSc

Disclosures

June 12, 2007

In This Article

The Atherogenic Dyslipidemia Study

A total of 309 patients (70% men; mean age, 54 years) participated in the atherogenic dyslipidemia study, all fulfilling the entry criteria, which included:

At enrollment, mean triglycerides were elevated (average, 250 mg/dL) and HDL was reduced (average, < 40 mg/dL); 40% of patients were taking statins. After a 4-week placebo lead-in period on the National Cholesterol Education Program Therapeutic Lifestyle Changes diet,[3] patients were randomized to 12 weeks of active treatment with LY518674 10 micrograms (mcg), 25 mcg, 50 mcg, or 100 mcg; fenofibrate 200 mg; or placebo.

Summarized below, the 2 primary endpoints of the study were the percentage change in HDL cholesterol and the percentage change in triglycerides ( Table 1 ):

  • Triglycerides: Both fenofibrate and LY518674 markedly decreased triglyceride levels (32.8% and 34.9% to 41.7%, respectively).

  • The reduction with LY518674 was not statistically different from the effect produced by fenofibrate.

  • LDL: Both fenofibrate and LY518674 increased levels of LDL cholesterol, with an increase of 2.3% with fenofibrate and a significantly greater increase for LY518674 at the 50-mcg and 100-mcg doses (18.3% and 19.5%, respectively) (P ≤ .002).

  • HDL: Fenofibrate increased HDL levels by 14.4%. LY518674 showed an unusual dose-response pattern, with the lowest dose (10 mcg) producing a modest increase (9.6%) in HDL levels, a maximum increase occurring with the 25-mcg dose (15.8%), and lesser increases occurring at higher dosages. The 100-mcg dose of LY518674 produced only a 2.1% increase in HDL, which did not differ significantly from the effect of placebo and was smaller than that with fenofibrate.

Levels of apolipoprotein (Apo)A-I rose in parallel with HDL cholesterol, but levels of apoA-II rose with a dose-response relationship for LY518674.

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