Efficacy and safety of ABT-335 (fenofibric acid) in combination with simvastatin in patients with mixed dyslipidemia: a phase 3, randomized, controlled study.
BACKGROUND
Patients with mixed dyslipidemia often require combination therapy to effectively control lipid abnormalities. This study compared the effects of combination therapy with ABT-335 (a new formulation of fenofibric acid) and simvastatin to ABT-335 and simvastatin monotherapies on lipid and nonlipid parameters in patients with mixed dyslipidemia.


METHODS
This was a phase 3, multicenter, randomized, double-blind, active-controlled study. A total of 657 patients with mixed dyslipidemia (low-density lipoprotein cholesterol [LDL-C] > or =130 mg/dL, triglycerides [TGs] > or =150 mg/dL, and high-density lipoprotein cholesterol [HDL-C]<40 mg/dL [men] or <50 mg/dL [women]) were randomized to 12 weeks of treatment with ABT-335 + simvastatin (20 or 40 mg) combination therapy, ABT-335 monotherapy (135 mg), or simvastatin monotherapy (20, 40, or 80 mg).


RESULTS
Combination therapy resulted in significantly greater increases in HDL-C and decreases in TGs compared to the corresponding simvastatin monotherapy dose (P < .001) and decreases in LDL-C compared to ABT-335 monotherapy (P < .001). HDL-C increased 17.8% versus 7.2% and TGs decreased -37.4% versus -14.2% (ABT-335 + simvastatin 20 vs simvastatin 20); LDL-C decreased -24.0% versus -4.0% (ABT-335 + simvastatin 20 vs ABT-335). HDL-C increased 18.9% versus 8.5% and TGs decreased -42.7% versus -22.4% (ABT-335 + simvastatin 40 vs simvastatin 40); LDL-C decreased -25.3% versus -4.0% (ABT-335 + simvastatin 40 vs ABT-335). Twelve-week treatment with combination therapy was generally well tolerated with a safety profile consistent with ABT-335 and simvastatin monotherapies. No cases of rhabdomyolysis were reported.


CONCLUSIONS
For patients with mixed dyslipidemia, combination therapy provided more effective control of multiple lipid parameters than either monotherapy alone, with a safety profile similar to both monotherapies.
Mohiuddin
Syed M
SM
The Creighton Cardiac Center, Omaha, NE 68131, USA. smm@creighton.edu
Pepine
Carl J
CJ
Kelly
Maureen T
MT
Buttler
Susan M
SM
Setze
Carolyn M
CM
Sleep
Darryl J
DJ
Stolzenbach
James C
JC
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D050171:Dyslipidemias / Q000188:drug therapy*; D005260:Female; D011345:Fenofibrate / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D000960:Hypolipidemic Agents / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D019821:Simvastatin / Q000627:therapeutic use*; D055815:Young Adult
C533234:2-(4-(4-chlorobenzoyl)phenoxy)-2-methylpropanoic acid; D000960:Hypolipidemic Agents; D019821:Simvastatin; C006012:fenofibric acid; D011345:Fenofibrate