New fibrate effective in treating mixed dyslipidemia when combined with rosuvastatin
An investigational fenofibric acid molecule (ABT-335), submitted for approval to the US Food and Drug Administration, treats mixed dyslipidemia in patients with type 2 diabetes better when used in combination with rosuvastatin than rosuvastatin therapy alone, said Peter H. Jones, MD, associate professor, Center for Cardiovascular Disease Prevention, Methodist DeBakey Heart Center, Houston, Texas.
The combination of ABT-335 and rosuvastatin was evaluated in a subgroup of 276 patients with type 2 diabetes who were part of a larger phase 3 study of more than 1400 patients with mixed dyslipidemia. Subjects enrolled had baseline low-density lipoprotein (LDL) cholesterol levels ≥130 mg/dL, high-density lipoprotein (HDL) cholesterol levels <40 mg/dL for men and <50 mg/dL for women, and triglyceride levels >150 mg/dL. Patients were randomized in a double-blind fashion to 12 weeks of ABT-335 (135 mg) combined with either 10 mg or 20 mg of rosuvastatin, ABT-335 alone (135 mg), or rosuvastatin monotherapy (10 mg, 20 mg, or 40 mg). The 40-mg rosuvastatin arm was included only to assess safety.
In the subanalysis of patients with type 2 diabetes, the combination of ABT-335 and 10 mg of rosuvastatin increased HDL cholesterol by 21% compared with a 6.6% increase with 10 mg of rosuvastatin alone ( = .001). The combination decreased triglycerides by 44.7%, whereas 10 mg of rosuvastatin monotherapy decreased triglycerides by 37.1% ( = .002). LDL cholesterol decreased by 37.1% with combination therapy compared with a 43.6% decline with 10 mg of rosuvastatin alone.
The combination of ABT-335 and 20 mg of rosuvastatin was associated with an increase in HDL cholesterol of 17.6% compared with an increase of 12.2% with 20 mg of rosuvastatin alone = .214), and the combination decreased triglycerides by 42.4% compared with a 26.8% decrease with 20 mg of rosuvastatin alone = .002). LDL cholesterol decreased more with 20 mg of rosuvastatin alone compared with the combination of 20 mg of rosuvastatin and ABT-335 (44.7% vs 37.4%).
"Patients with type 2 diabetes don't have just an LDL problem; they have small, dense LDL and too little HDL. This agent [ABT-335] in combination with rosuvastatin has the ability to achieve the American Diabetes Association goals for HDL, LDL, non-HDL cholesterol, and triglycerides in patients with diabetic dyslipidemia, more so than monotherapy," said Dr Jones. Because fibrates increase LDL particle size, making them less atherogenic, LDL cholesterol levels are not lowered. Statins do not change LDL particle size, noted Dr Jones. ABT-335 was associated with reductions in apolipoprotein B and non-HDL cholesterol, he added.
"Every patient with diabetic dyslipidemia should be on a statin, but a statin alone is not enough for patients with low HDL and high triglycerides," said Dr Jones. The safety of the combination was not different from statin monotherapy, he said. An elevation in blood creatinine was experienced by 1.9% to 5.8% of patients treated with combination therapy (10 mg and 20 mg of rosuvastatin, respectively), and myalgia was reported by 1.9% to 3.8% of patients who received combination treatment.