A Multicenter Randomized Parallel-group Study to Investigate the Efficacy of a Combination of Rosuvastatin and Fenofibrate in the Patients With Diabetes or Atherosclerotic Vascular Diseases With Metabolic Syndrome
A Multicenter Randomized Parallel-group Study to Investigate the Efficacy of a Combination of Rosuvastatin and Fenofibrate in the Patients With Diabetes or Atherosclerotic Vascular Diseases With Metabolic Syndrome
Diabetic patients have an excess risk of mortality due to cardiovascular diseases (CVD)
 compared to non-diabetics. Cardiovascular disease mortality rate is reportedly on the rise in
 several countries in the region, including urban China, Malaysia, Korea and Taiwan.
 Cardiovascular diseases and stroke are always the number 2 and 3 killers for Taiwanese
 population in recent years, and they really cost much from our medical resource. For treating
 dyslipidemia, one of the major risk factor for CVD, statins have been well documented to
 reduce CV deaths both for primary and secondary prevention in several large-scale trials. It
 has been reported that the clinical benefits of treating dyslipidemia in patients with
 diabetes mellitus should be at least equivalent to the benefits observed among those with
 cardiovascular disease. A meta-analysis of seven trials of statins found that treatment for
 about 5 years resulted in a 25% reduction in the combined outcome of coronary heart disease
 death and non-fatal myocardial infarction. Fibrates are another group of hypolipidemic drugs
 that regulate lipid metabolism and are used quite often in daily practice for diabetic
 dyslipidemia, because of its beneficial effect to reduce high TG and increase low HDL-C,
 which are the characteristic lipid abnormalities commonly seen in the patients with diabetes
 or metabolic syndrome. However, in recently published FIELD study, fenofibrate did not
 significantly reduce the risk of the primary outcome of coronary events in 9,795 participants
 with type 2 diabetes mellitus. The higher rate of starting statin therapy in patients
 allocated placebo might have masked a moderately larger treatment benefit. Furthermore, all
 the treatment trials to back up the lipid treatment guideline were conducted in Caucasians
 and no data about the combination therapy with fibrate and statin was published before.
-  Men or women aged 20-79 years

 -  with definite DM or atherosclerotic vascular diseases with metabolic syndrome (defined
 as the presence of three or more of the following risk factors:

 -  abdominal obesity [waist circumference > 90 cm in men or > 80 cm in women],

 -  triglycerides > 150 mg/dL, HDL-cholesterol < 40 mg/dL in men or < 50 mg/dL in women,
 blood pressure > 130/85 mm Hg,

 -  or fasting glucose > 100 mg/dL) and who are qualified for lipid lowering therapy
 according to the Taiwanese national guidelines (LDL-C 130-190 mg/dL or TG 200-500
 mg/dL with HDL-C < 40 mg/dL or TC/HDL-C > 5) will be eligible. The main exclusion
 criteria will be any known contraindications to statin or fibrate therapy,

 -  previous intolerance to statin or fibrate in low or high doses,

 -  liver enzyme levels more than 3 times the upper limit of normal,

 -  pregnancy or breastfeeding,

 -  nephrotic syndrome,

 -  uncontrolled diabetes mellitus (HbA1c > 9),

 -  uncontrolled hypothyroidism,

 -  plasma LDL-C level higher than 190 mg/dL or triglyceride level higher than 500 mg/dL,

 -  coronary heart disease event or revascularisation within a month, congestive heart
 failure (New York Heart Association classification IIIb or IV),

 -  hemodynamically important valvular heart disease, gastrointestinal conditions
 affecting absorption of drugs,

 -  treatment with other drugs that seriously affect the pharmacokinetics of statins or
 fibrate,

 -  unexplained creatine phosphokinase concentrations six or more times the upper limit of
 normal,

 -  life-threatening malignancy,

 -  treatment with immuno suppressive or other lipid lowering drugs.

 -  Patients previously treated with monotherapy with statins or fibrates will be
 qualified if they have not already had titration to a dose higher than the equivalent
 of 5 mg/d of rosuvastatin or 80 mg/d of SFC fenofibrate.