Efficacy and safety of ABT-335 (fenofibric acid) in combination with simvastatin in patients with mixed dyslipidemia: A phase 3, randomized, controlled study

被引:64
作者
Mohiuddin, Syed M. [1 ]
Pepine, Carl J. [2 ]
Kelly, Maureen T. [3 ]
Buttler, Susan M. [3 ]
Setze, Carolyn M. [3 ]
Sleep, Darryl J. [3 ]
Stolzenbach, James C. [3 ]
机构
[1] Creighton Cardiac Ctr, Omaha, NE 68131 USA
[2] Univ Florida, Gainesville, FL USA
[3] Abbott, Abbott Pk, IL USA
关键词
COMBINED HYPERLIPIDEMIA; MANAGEMENT; PREVENTION; RISK;
D O I
10.1016/j.ahj.2008.08.027
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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] -130 mg/dL, triglycerides [TGs] >= 130 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. Conclusion 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. (Am Heart J 2009;157:195-203.)
引用
收藏
页码:195 / 203
页数:9
相关论文
共 19 条
[1]  
*ABB, 2007, TRICOR FEN TABL PROD
[2]  
*AM HEART ASS, 2004, EAT PLAN HLTH AM OUR
[3]  
Antman EM, 2008, J AM COLL CARDIOL, V51, P2028, DOI [10.1016/j.jacc.2008.04.002, 10.1016/j.jacc.2007.10.001]
[4]   Fibrates: What have we learned in the past 40 years? [J].
Backes, James M. ;
Gibson, Cheryl A. ;
Ruisinger, Janelle E. ;
Moriarty, Patrick M. .
PHARMACOTHERAPY, 2007, 27 (03) :412-424
[5]  
Buse JB, 2007, DIABETES CARE, V30, P162, DOI [10.2337/dc07-9917, 10.1161/CIRCULATIONAHA.106.179294]
[6]   The role of fibrates in managing hyperlipidemia: mechanisms of action and clinical efficacy. [J].
Fazio S. ;
Linton M.F. .
Current Atherosclerosis Reports, 2004, 6 (2) :148-157
[7]   2007 chronic angina focused update of the ACC/AHA 2002 guidelines for the management of patients with chronic stable angina [J].
Fraker, Theodore D. ;
Fihn, Stephan D. .
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 2007, 50 (23) :2264-2274
[8]  
Genest J, 2003, CAN MED ASSOC J, V169, P921
[9]   Combination therapy of dyslipidemia [J].
Goldberg A.C. .
Current Treatment Options in Cardiovascular Medicine, 2007, 9 (4) :249-258
[10]   Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) Final Report [J].
Grundy, SM ;
Becker, D ;
Clark, LT ;
Cooper, RS ;
Denke, MA ;
Howard, WJ ;
Hunninghake, DB ;
Illingworth, R ;
Luepker, RV ;
McBride, P ;
McKenney, JM ;
Pasternak, RC ;
Stone, NJ ;
Van Horn, L ;
Brewer, HB ;
Cleeman, JI ;
Ernst, ND ;
Gordon, D ;
Levy, D ;
Rifkind, B ;
Rossouw, JE ;
Savage, P ;
Haffner, SM ;
Orloff, DG ;
Proschan, MA ;
Schwartz, JS ;
Sempos, CT ;
Shero, ST ;
Murray, EZ ;
Keller, SA ;
Jehle, AJ .
CIRCULATION, 2002, 106 (25) :3143-3421