Skip to main content
SpringerLink
Log in

Fenofibrate

A Review of its Use in Primary Dyslipidaemia, the Metabolic Syndrome and Type 2 Diabetes Mellitus

  • Adis Drug Evaluation
  • Published:
Drugs Aims and scope Submit manuscript

Abstract

Fenofibrate is a fibric acid derivative indicated for use in the treatment of primary hypercholesterolaemia, mixed dyslipidaemia and hypertriglyceridaemia in adults who have not responded to nonpharmacological measures. Its lipid-modifying effects are mediated by activation of peroxisome proliferator-activated receptor-α. Fenofibrate also has nonlipid (i.e. pleiotropic) effects (e.g. it reduces fibrinogen, C-reactive protein and uric acid levels and improves flow-mediated dilatation).

Fenofibrate improves lipid levels (in particular triglyceride [TG] and high-density lipoprotein-cholesterol [HDL-C] levels) in patients with primary dyslipidaemia. Its lipid-lowering profile means that fenofibrate is particularly well suited for use in atherogenic dyslipidaemia (characterised by high TG levels, low HDL-C levels and small, dense low-density lipoprotein [LDL] particles), which is commonly seen in patients with the metabolic syndrome and type 2 diabetes mellitus. Indeed, fenofibrate improves the components of atherogenic dyslipidaemia in patients with these conditions, including a shift from small, dense LDL particles to larger, more buoyant LDL particles. Greater improvements in lipid levels are seen when fenofibrate is administered in combination with an HMG-CoA reductase inhibitor (statin) or in combination with ezetimibe, compared with monotherapy with these agents. In the DAIS study, fenofibrate significantly slowed the angiographic progression of focal coronary atherosclerosis in patients with type 2 diabetes. In terms of clinical outcomes, although no significant reduction in the risk of coronary events was seen with fenofibrate in the FIELD trial in patients with type 2 diabetes, treatment was associated with a significantly reduced risk of total cardiovascular disease (CVD) events, primarily through the prevention of non-fatal myocardial infarction and coronary revascularisation. Subgroup analyses revealed significant reductions in total CVD events and coronary heart disease events in patients with no previous CVD, suggesting a potential role for primary prevention with fenofibrate in patients with early type 2 diabetes. Improvements were also seen in microvascular outcomes with fenofibrate in the FIELD trial. Fenofibrate is generally well tolerated, both as monotherapy and when administered in combination with a statin. Combination therapy with fenofibrate plus a statin appears to be associated with a low risk of rhabdomyolysis; no cases of rhabdomyolysis were reported in patients receiving such therapy in the FIELD trial. Thus, fenofibrate is a valuable lipid-lowering agent, particularly in patients with atherogenic dyslipidaemia.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Table I
Table II
Fig. 1
Table III
Table IV
Table V
Fig. 2
Fig. 3
Fig. 4
Table VI
Fig. 5
Table VII
Table VIII

Similar content being viewed by others

Notes

  1. Trade names for the various fenofibrate formulations include Catalip®, Fulcro®, Lipanthyl®, Lipantil®, Lipidil®, Lipcor®, Secalip®, Supralip® and Tricor®. The use of trade names is for product identification purposes only and does not imply endorsement.

References

  1. National Cholesterol Education Program Expert Panel. 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. Circulation 2002 Dec 17; 106 (25): 3143–421

    Google Scholar 

  2. Fruchart J-C, Duriez P. Mode of action of fibrates in the regulation of triglycerides and HDL-cholesterol metaboism. Drugs Today 2006; 42 (1): 39–64

    Article  CAS  Google Scholar 

  3. Jellinger PS. The American Association of Clinical Endocrinologists medical guidelines for clinical practice for the diagnosis and treatment of dyslipidemia and prevention of atherogenesis: 2002 amended version. Endocr Pract 2000 Mar/Apr; 6 (2): 1–52

    Google Scholar 

  4. Grundy SM, Cleeman JI, Merz CNB, et al. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. Circulation 2004 Jul 13; 110: 227–39

    Article  PubMed  Google Scholar 

  5. Bloomfield HE. The role of fibrates in a statin world. Arch Intern Med 2006 Apr 10; 166: 715–6

    Article  PubMed  Google Scholar 

  6. Ford ES, Giles WH, Dietz WH. Prevalence of the metabolic syndrome among US adults: findings from the third National Health and Nutrition Examination Survey. JAMA 2002 Jan 16; 287 (3): 356–9

    Article  PubMed  Google Scholar 

  7. Ford ES, Giles WH, Mokdad AH, et al. Increasing prevalence of the metabolic syndrome among US adults. Diabetes Care 2004 Oct; 27 (10): 2444–249

    Article  PubMed  Google Scholar 

  8. Grundy SM, Brewer HB, Cleeman JI, et al. Definition of metabolic syndrome: report of the National Heart, Lung, and Blood Institute/American Heart Association Conference on Scientific Issues Related to Definition. Circulation 2004 Jan 27; 109: 433–8

    Article  PubMed  Google Scholar 

  9. Grundy SM. Drug therapy of the metabolic syndrome: minimizing the emerging crisis in polypharmacy. Nat Rev Drug Discov 2006 Apr; 5 (4): 295–309

    Article  PubMed  CAS  Google Scholar 

  10. Wild S, Roglic G, Green A, et al. Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes Care 2004 May; 27 (5): 1047–53

    Article  PubMed  Google Scholar 

  11. Beckman JA, Creager MA, Libby P. Diabetes and atherosclerosis: epidemiology, pathophysiology, and management. JAMA 2002 May 15; 287 (19): 2570–81

    Article  PubMed  CAS  Google Scholar 

  12. Nesto RW. Beyond low-density lipoprotein: addressing the atherogenic lipid triad in type 2 diabetes mellitus and the metabolic syndrome. Am J Cardiovasc Drugs 2005; 5 (6): 379–87

    Article  PubMed  CAS  Google Scholar 

  13. National Institute of Diabetes and Digestive and Kidney Diseases. National Diabetes Statistics [online]. Available from URL: http://diabetes.niddk.nih.gov/dm/pubs/statistics [Accessed 2006 May 12]

  14. Donnelly R, Emslie-Smith AM, Gardner ID, et al. Vascular complications of diabetes. Br Med J 2000 Apr 15; 320: 1062–6

    Article  CAS  Google Scholar 

  15. American Diabetes Association. Standards of medical care in diabetes. Diabetes Care 2005 Jan; 28 Suppl. 1: S4–36

    Article  Google Scholar 

  16. Khera A, McGuire DK. Management of diabetic dyslipidemia: need for reappraisal of the goals. Am J Cardiovasc Drugs 2005; 5 (2): 83–91

    Article  PubMed  CAS  Google Scholar 

  17. Munoz A, Guichard JP, Reginault P. Micronised fenofibrate. Atherosclerosis 1994 Oct; 110 Suppl.: S45–8

    Google Scholar 

  18. Sauron R, Wilkins M, Jessent V, et al. Absence of a food effect with a 145 mg nanoparticle fenofibrate tablet formulation. Int J Clin Pharmacol Ther 2006 Feb; 44 (2): 64–70

    PubMed  CAS  Google Scholar 

  19. Fournier Pharmaceuticals Ltd. Lipantil® Micro 67: summary of product characteristics [online]. Available from URL: http:// emc.medicines.org.uk [Accessed 2006 Apr 4]

  20. Fournier Pharmaceuticals Ltd. Lipantil® Micro 200: summary of product characteristics [online]. Available from URL: http:// emc.medicines.org.uk [Accessed 2006 Mar 31]

  21. Fournier Pharmaceuticals Ltd. Lipantil® Micro 267: summary of product characerteristics [online]. Available from URL: http://emc.medicines.org.uk [Accessed 2006 Apr 6]

  22. Fournier Pharmaceuticals Ltd. Supralip® 160mg: summary of product characteristics [online]. Available from URL: http:// emc.medicines.org.uk [Accessed 2006 Apr 6]

  23. Data on file, Fournier Pharmaceuticals Ltd, 2006

  24. Abbott Laboratories. Tricor® 48mg and 145mg (fenofibrate tablets): prescribing information [online]. Available from URL: http://tricortablets.com/ [Accessed 2006 Apr 3]

  25. Schoonjans K, Martin G, Staels B, et al. Peroxisome proliferator-activated receptors, orphans with ligands and functions. Curr Opin Lipidol 1997 Jun; 8 (3): 159–66

    Article  PubMed  CAS  Google Scholar 

  26. Arakawa R, Tamehiro N, Nishimaki-Mogami T, et al. Fenofibric acid, an active form of fenofibrate, increases apolipoprotein A-I-mediated high-density lipoprotein biogenesis by enhancing transcription of ATP-binding cassette transporter A1 gene in a liver X receptor-dependent manner. Arterioscler Thromb Vasc Biol 2005 Jun; 25 (6): 1193–7

    Article  PubMed  CAS  Google Scholar 

  27. Duez H, Lefebvre B, Poulain P, et al. Regulation of human apoA-I by gemfibrozil and fenofibrate through selective peroxisome proliferator-activated receptor a modulation. Arterioscler Thromb Vasc Biol 2005 Mar; 25 (3): 585–91

    Article  PubMed  CAS  Google Scholar 

  28. Chapman MJ. Fibrates: therapeutic review. Br J Diabetes Vasc Dis 2006 Jan–Feb; 6 (1): 11–18, 20

    Article  CAS  Google Scholar 

  29. Schoonjans K, Peinado-Onsurba J, Lefebvre A-M, et al. PPARα and PPARγ activators direct a distinct tissue-specific transcriptional response via a PPRE in the lipoprotein lipase gene. EMBO J 1996; 15 (19): 5336–48

    PubMed  CAS  Google Scholar 

  30. Haubenwallner S, Essenburg AD, Barnett BC, et al. Hypolipidemic activity of select fibrates correlates to changes in hepatic apolipoprotein C-III expression: a potential physiologic basis for their mode of action. J Lipid Res 1995 Dec; 36 (12): 2541–51

    PubMed  CAS  Google Scholar 

  31. Staels B, Vu-Dac N, Kosykh VA, et al. Fibrates downregulate apolipoprotein C-III expression independent of induction of peroxisomal acyl coenzyme A oxidase: a potential mechanism for the hypolipidemic action of fibrates. J Clin Invest 1995 Aug; 95: 705–12

    Article  PubMed  CAS  Google Scholar 

  32. Schoonjans K, Staels B, Auwerx J. The peroxisome proliferator activated receptors (PPARs) and their effects on lipid metabolism and adipocyte differentiation. Biochim Biophys Acta 1996; 1302: 93–109

    Article  PubMed  CAS  Google Scholar 

  33. Schoonjans K, Staels B, Auwerx J. Role of the peroxisome proliferator-activated receptor (PPAR) in mediating the effects of fibrates and fatty acids on gene expression. J Lipid Res 1996; 37: 907–25

    PubMed  CAS  Google Scholar 

  34. Guérin M, Bruckert E, Dolphin PJ, et al. Fenofibrate reduces plasma cholesteryl ester transfer from HDL to VLDL and normalizes the atherogenic, dense LDL profile in combined hyperlipidemia. Arterioscler Thromb Vasc Biol 1996 Jun; 16 (6): 763–72

    Article  PubMed  Google Scholar 

  35. Shepherd J, Caslake MJ, Lorimer AR, et al. Fenofibrate reduces low density lipoprotein catabolism in hypertriglyceridemic subjects. Arteriosclerosis 1985 Mar/Apr; 5 (2): 162–8

    Article  PubMed  CAS  Google Scholar 

  36. Caslake MJ, Packard CJ, Gaw A, et al. Fenofibrate and LDL metabolic heterogeneity in hypercholesterolemia. Arterioscler Thromb 1993 May; 13 (5): 702–11

    Article  PubMed  CAS  Google Scholar 

  37. Ikewaki K, Tohyama J, Nakata Y, et al. Fenofibrate effectively reduces remnants, and small dense LDL, and increases HDL particle number in hypertriglyceridemic men: a nuclear magnetic resonance study. J Atheroscler Thromb 2004; 11 (5): 278–85

    Article  PubMed  CAS  Google Scholar 

  38. Winkler K, Weltzien P, Friedrich I, et al. Qualitative effect of fenofibrate and quantitative effect of atorvastatin on LDL profile in combined hyperlipidaemia with dense LDL. Exp Clin Endocrinol Diabetes 2004; 112: 241–7

    Article  PubMed  CAS  Google Scholar 

  39. Berthou L, Duverger N, Emmanuel F, et al. Opposite regulation of human versus mouse apolipoprotein A-I by fibrates in human apolipoprotein A-I transgenic mice. J Clin Invest 1996; 97 (11): 2408–16

    Article  PubMed  CAS  Google Scholar 

  40. Vu-Dac N, Schoonjans K, Kosykh V, et al. Fibrates increase human apolipoprotein A-II expression through activation of the peroxisome proliferator-activated receptor. J Clin Invest 1995; 96: 741–50

    Article  PubMed  CAS  Google Scholar 

  41. Ji J, Barrett PHR, Johnson AG, et al. Lipid transfer proteins and apolipoprotein B-100 metabolism in the metabolic syndrome treated with fenofibrate [abstract no. We-P11:111]. Atherosclerosis 2006 Jun; 7 (3 Suppl.): 370

    Google Scholar 

  42. Kiyanagi T, Miyazaki T, Kume A, et al. Decrease in CETP activity by fenofibrate may increase LDL particle size measured by HPLC method in patients with coronary artery disease [abstract no. Th-P16:301]. Atherosclerosis 2006 Jun; 7 (3 Suppl.): 559

    Google Scholar 

  43. McPherson R, Agnani G, Lau P, et al. Role of Lp A-I and Lp A-I/A-II in cholesteryl ester transfer protein-mediated neutral lipid transfer: studies in normal subjects and in hypertriglyceridemic patients before and after fenofibrate therapy. Arterioscler Thromb Vasc Biol 1996 Nov; 16 (11): 1340–6

    Article  PubMed  CAS  Google Scholar 

  44. Bertolini S, Elicio N, Daga A, et al. Effect of a single daily dose treatment of fenofibrate on plasma lipoproteins in hyperlipoproteinaemia IIb. Eur J Clin Pharmacol 1988; 34: 25–8

    Article  PubMed  CAS  Google Scholar 

  45. Elisaf M, Tsimichodimos V, Bairaktari E, et al. Effect of micronized fenofibrate and losartan combination on uric acid metabolism in hypertensive patients with hyperuricemia. J Cardiovasc Pharmacol 1999 Jul; 34 (1): 60–3

    Article  PubMed  CAS  Google Scholar 

  46. Genest Jr J, Nguyen N-H, Theroux P, et al. Effect of micronized fenofibrate on plasma lipoprotein levels and hemostatic parameters of hypertriglyceridemic patients with low levels of high-density lipoprotein cholesterol in the fed and fasted state. J Cardiovasc Pharmacol 2000 Jan; 35 (1): 164–72

    Article  PubMed  CAS  Google Scholar 

  47. Haak T, Haak E, Kusterer K, et al. Fenofibrate improves microcirculation in patients with hyperlipidemia. Eur J Med Res 1998 Feb 21; 3 (1–2): 50–4

    PubMed  CAS  Google Scholar 

  48. Insua A, Massari F, Rodriguez Moncalvo JJ, et al. Fenofibrate or gemfibrozil for treatment of types IIa and IIb primary hyperlipoproteinemia: a randomized, double-blind, crossover study. Endocr Pract 2002 Mar/Apr; 8 (2): 96–101

    PubMed  Google Scholar 

  49. Kiortsis DN, Millionis H, Bairaktari E, et al. Efficacy of combination of atorvastatin and micronised fenofibrate in the treatment of severe mixed hyperlipidemia. Eur J Clin Pharmacol 2000 Dec; 56 (9-10): 631–5

    Article  CAS  Google Scholar 

  50. Ko HS, Kim CJ, Ryu WS. Effect of fenofibrate on lipoprotein(a) in hypertriglyceridemic patients: impact of change in triglyceride level and liver function. J Cardiovasc Pharmacol 2005 Oct; 46 (4): 405–11

    Article  PubMed  CAS  Google Scholar 

  51. Koh KK, Ahn JY, Han SH, et al. Effects of fenofibrate on lipoproteins, vasomotor function, and serological markers of inflammation, plaque stabilization, and hemostasis. Atherosclerosis 2004 Jun; 174 (2): 379–83

    Article  CAS  Google Scholar 

  52. Koh KK, Quon MJ, Han SH, et al. Additive beneficial effects of fenofibrate combined with atorvastatin in the treatment of combined hyperlipidemia. J Am Coll Cardiol 2005 May 17; 45 (10): 1649–53

    Article  PubMed  CAS  Google Scholar 

  53. Koh KK, Han SH, Quon MJ, et al. Beneficial effects of fenofibrate to improve endothelial dysfunction and raise adiponectin levels in patients with primary hypertriglyceridemia. Diabetes Care 2005 Jun; 28 (6): 1419–24

    Article  PubMed  CAS  Google Scholar 

  54. Koh KK, Quon MJ, Han SH, et al. Additive beneficial effects of fenofibrate combined with candesartan in the treatment of hypertriglyceridemic hypertensive patients. Diabetes Care 2006 Feb; 29 (2): 195–201

    Article  PubMed  CAS  Google Scholar 

  55. Krempf M, Rohmer V, Farnier M, et al. Efficacy and safety of micronised fenofibrate in a randomised double-blind study comparing four doses from 200 mg to 400 mg daily with placebo in patients with hypercholesterolemia. Diabetes Metab 2000 May; 26 (3): 184–91

    PubMed  CAS  Google Scholar 

  56. Lemieux I, Salomon H, Després J-P. Contribution of apo CIII reduction to the greater effect of 12-week micronized fenofibrate than atorvastatin therapy on triglyceride levels and LDL size in dyslipidemic patients. Ann Med 2003; 35 (6): 442–8

    Article  PubMed  CAS  Google Scholar 

  57. Malik J, Melenovsky V, Wichterle D, et al. Both fenofibrate and atorvastatin improve vascular reactivity in combined hyperlipidaemia (fenofibrate versus atorvastatin trial — FAT). Cardiovasc Res 2001 Nov; 52 (2): 290–8

    Article  PubMed  CAS  Google Scholar 

  58. Paragh G, Seres I, Harangi M, et al. The effect of micronised fenofibrate on paraoxonase activity in patients with coronary heart disease. Diabetes Metab 2003 Dec; 29 (6): 613–8

    Article  PubMed  CAS  Google Scholar 

  59. Rašlová K, Dubovská D, Mongiellová V, et al. Relationship between plasma fenofibric acid levels and the effect of micronized fenofibrate on cholesterol, low-density-lipoprotein cholesterol and apolipoprotein B in patients with primary hypercholesterolemia. Eur J Clin Pharmacol 1997 Apr; 52: 101–6

    Article  PubMed  Google Scholar 

  60. Sasaki J, Yamamoto K, Ageta M. Effects of fenofibrate on high-density lipoprotein particle size in patients with hyperlipidemia: a randomized, double-blind, placebo-controlled, multicenter, crossover study. Clin Ther 2002 Oct; 24 (10): 1614–26

    Article  PubMed  CAS  Google Scholar 

  61. Tsimihodimos V, Kostoula A, Kakafika A, et al. Effect of fenofibrate on serum inflammatory markers in patients with high triglyceride values. J Cardiovasc Pharmacol Ther 2004 Mar; 9 (1): 27–33

    Article  PubMed  CAS  Google Scholar 

  62. Tsimihodimos V, Tambaki A, Tzovaras V, et al. Comparison of the effects of atorvastatin and fenofibrate on apolipoprotein B-containing lipoprotein subfractions in patients with combined dyslipidemia. Hellenic J Cardiol 2004; 45 (4): 225–30

    Google Scholar 

  63. Watts GF, Barrett PHR, Ji J, et al. Differential regulation of lipoprotein kinetics by atorvastatin and fenofibrate in subjects with the metabolic syndrome. Diabetes 2003 Mar; 52: 803–11

    Article  PubMed  CAS  Google Scholar 

  64. Watts GF, Ji J, Chan DC, et al. Relationships between changes in plasma lipid transfer proteins and apolipoprotein B-100 kinetics during fenofibrate treatment in the metabolic syndrome. Clin Sci (Lond) 2006 May 16; 111 (3): 193–9

    Article  CAS  Google Scholar 

  65. Athyros VG, Papageorgiou AA, Athyrou VV, et al. Atorvastatin and micronized fenofibrate alone and in combination in type 2 diabetes with combined hyperlipidemia. Diabetes Care 2002 Jul;25 (7): 1198–202

    Article  PubMed  CAS  Google Scholar 

  66. Cavallero E, Dachet C, Assadolahi F, et al. Micronized fenofibrate normalizes the enhanced lipidemic response to a fat load in patients with type 2 diabetes and optimal glucose control. Atherosclerosis 2003 Jan; 166 (1): 151–61

    Article  PubMed  CAS  Google Scholar 

  67. Feher MD, Caslake M, Foxton J, et al. Atherogenic lipoprotein phenotype in type 2 diabetes: reversal with micronised fenofibrate. Diabetes Metab Res Rev 1999 Nov–Dec 31; 15 (6): 395–9

    Article  PubMed  CAS  Google Scholar 

  68. Playford DA, Watts GF, Best JD, et al. Effect of fenofibrate on brachial artery flow-mediated dilatation in type 2 diabetes mellitus. Am J Cardiol 2002 Dec 1; 90: 1254–7

    Article  PubMed  CAS  Google Scholar 

  69. Forcheron F, Cachefo A, Thevenon S, et al. Mechanisms of the triglyceride- and cholesterol-lowering effect of fenofibrate in hyperlipidemic type 2 diabetic patients. Diabetes 2002 Dec; 51: 3486–91

    Article  PubMed  CAS  Google Scholar 

  70. Chinetti G, Gbaguidi FG, Griglio S, et al. CLA-1/SR-BI is expressed in atherosclerotic lesion macrophages and regulated by activators of peroxisome proliferator-activated receptors. Circulation 2000 May 23; 101 (20): 2411–7

    Article  PubMed  CAS  Google Scholar 

  71. Zambon A, Gervois P, Pauletto P, et al. Modulation of hepatic inflammatory risk markers of cardiovascular diseases by PPAR-α activators: clinical and experimental evidence. Arterioscler Throm Vasc Biol 2006 May; 26 (5): 977–86

    Article  CAS  Google Scholar 

  72. Milionis HJ, Papakostas J, Kakafika A, et al. Comparative effects of atorvastatin, simvastatin, and fenofibrate on serum homocysteine levels in patients with primary hyperlipidaemia. J Clin Pharmacol 2003 Aug; 43 (8): 825–30

    Article  PubMed  CAS  Google Scholar 

  73. Wang T-D, Chen W-J, Lin J-W, et al. Efficacy of fenofibrate and simvastatin on endothelial function and inflammatory markers in patients with combined hyperlipidemia: relations with baseline lipid profiles. Atherosclerosis 2003 Oct; 170 (2): 315–23

    Article  PubMed  CAS  Google Scholar 

  74. Yesilbursa D, Serdar A, Saltan Y, et al. The effect of fenofibrate on serum paraoxonase activity and inflammatory markers in patients with combined hyperlipidemia. Kardiol Pol 2005 Jun; 62 (6): 526–30

    PubMed  Google Scholar 

  75. Bissonnette R, Treacy E, Rozen R, et al. Fenofibrate raises plasma homocysteine levels in the fasted and fed states. Atherosclerosis 2001 Apr; 155 (2): 455–62

    Article  PubMed  CAS  Google Scholar 

  76. Capell WH, DeSouza CA, Poirier P, et al. Short-term triglyceride lowering with fenofibrate improves vasodilator function in subjects with hypertriglyceridemia. Arterioscler Thromb Vasc Biol 2003 Feb; 23: 307–13

    Article  PubMed  CAS  Google Scholar 

  77. Coban E, Ozdogan M, Yazicioglu G, et al. The effect of fenofibrate on the levels of high sensitivity C-reactive protein in dyslipidaemic hypertensive patients. Int J Clin Pract 2005 Apr; 59 (4): 415–8

    Article  PubMed  CAS  Google Scholar 

  78. Dierkes J, Westphal S, Luley C. Serum homocysteine increases after therapy with fenofibrate or bezafibrate [letter]. Lancet 1999 Jul 17; 354 (9174): 219–20

    Article  PubMed  CAS  Google Scholar 

  79. de Lorgeril M, Salen P, Paillard F, et al. Lipid-lowering drugs and homocysteine [letter]. Lancet 1999 Jan 16; 353 (9148): 209–10

    Article  PubMed  Google Scholar 

  80. Ellen RLB, McPherson R. Long-term efficacy and safety of fenofibrate and a statin in the treatment of combined hyperlipidemia. Am J Cardiol 1998 Feb 26; 81 (4A): 60–5B

    Article  Google Scholar 

  81. Kowalski J, Okopień B, Madej A, et al. Effects of atorvastatin, simvastatin, and fenofibrate therapy on monocyte chemoattractant protein-1 secretion in patients with hyperlipidemia. Eur J Clin Pharmacol 2003 Jul; 59 (3): 189–93

    Article  PubMed  CAS  Google Scholar 

  82. Kowalski J, Okopien B, Madej A, et al. Effects of fenofibrate and simvastatin on plasma sICAM-1 and MCP-1 concentrations in patients with hyperlipoproteinemia. Int J Clin Pharmacol Ther 2003 Jun; 41 (6): 241–7

    PubMed  CAS  Google Scholar 

  83. Mackness MI, Phuntuwate W, Suthisisang C, et al. Effect of fenofibrate treatment on paraoxonase 1 [abstract no. A68]. Diabet Med 2006 Mar 1; 23 Suppl. 2: 18–9

    Google Scholar 

  84. Noguchi Y, Tatsuno I, Suyama K, et al. Effect of fenofibrate on uric acid metabolism in Japanese hyperlipidemic patients. J Atheroscler Thromb 2004; 11 (6): 335–40

    Article  PubMed  CAS  Google Scholar 

  85. Okopien B, Cwalina L, Lebek M, et al. Effects of fibrates on plasma prothrombotic activity in patients with type IIb dyslipidemia. Int J Clin Pharmacol Ther 2001 Dec; 39 (12): 551–7

    PubMed  CAS  Google Scholar 

  86. Okopien B, Krysiak R, Haberka M, et al. Effect of monthly atorvastatin and fenofibrate treatment on monocyte chemoattractant protein-1 release in patients with primary mixed dyslipidemia. J Cardiovasc Pharmacol 2005 Apr; 45 (4): 314–20

    Article  PubMed  CAS  Google Scholar 

  87. Okopien B, Kowalski J, Krysiak R, et al. Monocyte suppressing action of fenofibrate. Pharmacol Rep 2005; 57 (3): 367–72

    PubMed  CAS  Google Scholar 

  88. Pfützner A, Ambrosch A, Forst T, et al. The influence of micronized fenofibrate on cardiovascular risk factors [in German]. Z Allg Med 1994; 70: 510–5

    Google Scholar 

  89. Ramjattan BR, Callaghan DJG, Theiss U. Efficacy and tolerability of a ‘suprabioavailable’ formulation of fenofibrate in patients with dyslipidemia: a pooled analysis of two open-label trials. Clin Ther 2002 Jul; 24 (7): 1105–16

    Article  PubMed  CAS  Google Scholar 

  90. Saklamaz A, Comlekci A, Temiz A, et al. The beneficial effects of lipid-lowering drugs beyond lipid-lowering effects: a comparative study with pravastatin, atorvastatin, and fenofibrate in patients with type Ha and type IIb hyperlipidemia. Metabolism 2005 May; 54 (5): 677–81

    Article  PubMed  CAS  Google Scholar 

  91. Staels B, Koenig W, Habib A, et al. Activation of human aortic smooth-muscle cells is inhibited by PPARα but not by PPARγ activators. Nature 1998 Jun 25; 393 (6687): 790–3

    Article  PubMed  CAS  Google Scholar 

  92. Undas A, Celinska-Löwenhoff M, Domagala TB, et al. Early antithrombotic and anti-inflammatory effects of simvastatin versus fenofibrate in patients with hypercholesterolemia. Thromb Haemost 2005 Jul 1; 94 (1): 193–9

    PubMed  CAS  Google Scholar 

  93. Westphal S, Dierkes J, Luley C. Effects of fenofibrate and gemfibrozil on plasma homocysteine [letter]. Lancet 2001 Jul 7; 358 (9275): 39–40

    Article  PubMed  CAS  Google Scholar 

  94. Yang T-L, Chen M-F, Xia X, et al. Effect of fenofibrate on the level of asymmetric dimethylarginine in individuals with hypertriglyceridemia. Eur J Clin Pharmacol 2006; 62: 179–84

    Article  PubMed  CAS  Google Scholar 

  95. Ye P, Li J-J, Su G, et al. Effects of fenofibrate on inflammatory cytokines and blood pressure in patients with hypertriglyceridemia [letter]. Clin Chim Acta 2005 Jun; 356 (1): 229–32

    Article  PubMed  CAS  Google Scholar 

  96. Belfort RS, Berria R, DeFronzo R, et al. Fenofibrate improves the atherogenic lipid profile and markers of vascular inflammation independent of changes in insulin sensitivity in hypertriglyceridemic subjects with the metabolic syndrome [abstract no. 620]. Diabetologia 2004 Aug; 47 Suppl. 1: A225–6

    Article  Google Scholar 

  97. Idzior-Walus B, Sieradzki J, Rostworowski W, et al. Effects of comicronised fenofibrate on lipid and insulin sensitivity in patients with polymetabolic syndrome X. Eur J Clin Invest 2000 Oct; 30 (10): 871–8

    Article  PubMed  CAS  Google Scholar 

  98. Rosenson RS, Huskin AL, Wolff DA. Fenofibrate reduces postprandial cytokine production in metabolic syndrome patients [abstract no. 3789]. Circulation 2005 Oct 25; 112 (17 Suppl.): 818. Plus poster presented at the 78th Scientific Sessions of the American Heart Association; 2005 Nov 13–16; Dallas (TX)

    Google Scholar 

  99. Okopień B, Krysiak R, Herman ZS. Effects of short-term fenofibrate treatment on circulating markers of inflammation and hemostasis in patients with impaired glucose tolerance. J Clin Endocrinol Metab 2006 May; 91 (5): 1770–8

    Article  PubMed  CAS  Google Scholar 

  100. Genest J, Frohlich J, Steiner G. Effect of fenofibrate-mediated increase in plasma homocysteine on the progression of coronary artery disease in type 2 diabetes mellitus. Am J Cardiol 2004 Apr 1; 93 (7): 848–53

    Article  PubMed  CAS  Google Scholar 

  101. Rosenson RS, Huskin AL, Wolff DA. Adiponectin and the anti-inflammatory effects of fenofibrate in patients with hypertriglyceridemia and the metabolic syndrome [abstract no. Tu-W27:5]. Atherosclerosis 2006 Jun; 7 (3 Suppl.): 175

    Google Scholar 

  102. Diabetes Atherosclerosis Intervention Study Investigators. Effect of fenofibrate on progression of coronary-artery disease in type 2 diabetes: the Diabetes Atherosclerosis Intervention Study, a randomised study. Lancet 2001 Mar 24; 357 (9260): 905–10

    Article  Google Scholar 

  103. Bergman AJ, Murphy G, Burke J, et al. Simvastatin does not have a clinically significant pharmacokinetic interaction with fenofibrate in humans. J Clin Pharmacol 2004 Sep; 44 (9): 1054–62

    Article  PubMed  CAS  Google Scholar 

  104. Martin PD, Dane AL, Schneck DW, et al. An open-label, randomized, three-way crossover trial of the effects of coadministration of rosuvastatin and fenofibrate on the pharmacokinetic properties of rosuvastatin and fenofibric acid in healthy male volunteers. Clin Ther 2003 Feb; 25 (2): 459–71

    Article  PubMed  CAS  Google Scholar 

  105. Davidson MH. Statin/fibrate combination in patients with metabolic syndrome or diabetes: evaluating the risks of pharmacokinetic drug interactions. Expert Opin Drug Saf 2006; 5 (1): 145–56

    Article  PubMed  CAS  Google Scholar 

  106. Whitfield LR, Abel R, Hartman D, et al. Effects of co-administration of gemfibrozil and fenofibrate on the pharmacokinetic profile of atorvastatin and major metabolites [abstract no. 547-P]. Diabetes 2005 Jun; 54 Suppl. 1: A135

    Google Scholar 

  107. Gustavson LE, Schweitzer SM, Koehne-Voss S, et al. The effects of multiple doses of fenofibrate on the pharmacokinetics of pravastatin and its 3α-hydroxy isomeric metabolite. J Clin Pharmacol 2005 Aug; 45 (8): 947–53

    Article  PubMed  CAS  Google Scholar 

  108. Pan W-J, Gustavson LE, Achari R, et al. Lack of a clinically significant pharmacokinetic interaction between fenofibrate and pravastatin in healthy volunteers. J Clin Pharmacol 2000; 40: 316–23

    Article  PubMed  CAS  Google Scholar 

  109. Gustavson LE, Schweitzer SM, Burt DA, et al. Evaluation of the potential for pharmacokinetic interaction between fenofibrate and ezetimibe: a phase I, open-label, multiple-dose, three period crossover study in healthy subjects. Clin Ther 2006 Mar; 28 (3): 373–87

    Article  PubMed  CAS  Google Scholar 

  110. Kosoglou T, Statkevich P, Fruchart J-C, et al. Pharmacodynamic and pharmacokinetic interaction between fenofibrate and ezetimibe. Curr Med Res Opin 2004 Aug; 20 (8): 1197–207

    Article  PubMed  CAS  Google Scholar 

  111. Jones MR, Baker BA, Mathew P. Effect of colesevelam HCl on single-dose fenofibrate pharmacokinetics. Clin Pharmacokinet 2004; 43 (13): 943–50

    Article  PubMed  CAS  Google Scholar 

  112. Kajosaari LI, Backman JT, Neuvonen M, et al. Lack of effect of bezafibrate and fenofibrate on the pharmacokinetics and pharmacodynamics of repaglinide. Br J Clin Pharmacol 2004 Oct; 58 (4): 390–6

    Article  PubMed  CAS  Google Scholar 

  113. Boissonnat P, Salen P, Guidollet J, et al. The long-term effects of the lipid-lowering agent fenofibrate in hyperlipidemic heart transplant recipients. Transplantation 1994 Jul; 58 (2): 245–7

    PubMed  CAS  Google Scholar 

  114. Julius U, Schwartz T. Micronized fenofibrate in lipometabolism disorders [in German]. Therapiewoche 1994; 44 (25): 1442–5

    Google Scholar 

  115. Kornitzer M, Dramaix M, Vandenbroek MD. Efficacy and tolerance of 200 mg micronised fenofibrate administered over a 6-month period in hyperlipidaemic patients: an open Belgian multicenter study. Atherosclerosis 1994 Oct; 110 Suppl.: S49–54

    Article  PubMed  CAS  Google Scholar 

  116. März W, Schmitz H, Bach G, et al. Micronised fenofibrate: efficacy and tolerability in the treatment of isolated and combined dyslipidemia [in German]. Munch Med Wochenschr 1994 Nov 11; 136 (45): 690–4

    Google Scholar 

  117. Kirchgässler KU, Schmitz H, Bach G. Effectiveness and tolerability of 12-week treatment with micronised fenofibrate 200mg in a drug-monitoring programme involving 9884 patients with dyslipidaemia. Clin Drug Invest 1998 Mar; 15 (3): 197–204

    Article  Google Scholar 

  118. Zhu J, Ye P. A survey on the efficacy and tolerability of micronized fenofibrate in patients with dyslipidemia. Chin Med J 2003 Jun; 116 (6): 840–3

    PubMed  CAS  Google Scholar 

  119. Ducobu J, VanHaelst L, Salomon H. Comparison of micronized fenofibrate and pravastatin in patients with primary hyperlipidemia. J Cardiovasc Pharmacol 2003 Jan; 41 (1): 60–7

    Article  PubMed  CAS  Google Scholar 

  120. Farnier M, Bonnefous F, Debbas N, et al. Comparative efficacy and safety of micronized fenofibrate and simvastatin in patients with primary type IIa or IIb hyperlipidemia. Arch Intern Med 1994 Feb 28; 154: 441–9

    Article  PubMed  CAS  Google Scholar 

  121. Steinmetz A, Schwartz T, Hehnke U, et al. Multicenter comparison of micronized fenofibrate and simvastatin in patients with primary type IIA or IIB hyperlipoproteinemia. J Cardiovasc Pharmacol 1996; 27 (4): 563–70

    Article  PubMed  CAS  Google Scholar 

  122. Farnier M, Dejager S, and the French Fluvastatin Study Group. Effect of combined fluvastatin-fenofibrate therapy compared with fenofibrate monotherapy in severe primary hypercholesterolemia. Am J Cardiol 2000 Jan 1; 85 (1): 53–7

    Article  PubMed  CAS  Google Scholar 

  123. Grundy SM, Vega GL, Yuan Z, et al. Effectiveness and tolerability of simvastatin plus fenofibrate for combined hyperlipidemia (the SAFARI Trial). Am J Cardiol 2005 Feb 15; 95 (4): 462–8

    Article  PubMed  CAS  Google Scholar 

  124. Farnier M, Freeman MW, Macdonell G, et al. Efficacy and safety of the coadministration of ezetimibe with fenofibrate in patients with mixed hyperlipidaemia. Eur Heart J 2005 May; 26 (9): 897–905

    Article  PubMed  CAS  Google Scholar 

  125. McKenney J, Jones M, Abby S. Safety and efficacy of colesevelam hydrochloride in combination with fenofibrate for the treatment of mixed hyperlipidemia. Curr Med Res Opin 2005 Sep; 21 (9): 1403–12

    Article  PubMed  CAS  Google Scholar 

  126. Després J-P, Lemieux I, Salomon H, et al. Effects of micronized fenofibrate versus atorvastatin in the treatment of dyslipidaemic patients with low plasma HDL-cholesterol levels: a 12-week randomized trial. J Intern Med 2002 Jun; 251 (6): 490–9

    Article  PubMed  Google Scholar 

  127. Roth E, Farnier M, Gil-Extremera B, et al. Coadministration of ezetimibe/simvastatin and fenofibrate is an efficacious and well-tolerated treatment for patients with mixed hyperlipidemia [abstract no. 2246-PO]. Diabetes 2006 Jun; 55 Suppl. 1: 519

    Google Scholar 

  128. Packard KA, Backes JM, Lenz TL, et al. Comparison of gemfibrozil and fenofibrate in patients with dyslipidemic coronary heart disease. Pharmacotherapy 2002 Dec; 22 (12): 1527–32

    Article  PubMed  Google Scholar 

  129. Levin A, Duncan L, Djurdjev O, et al. A randomized placebocontrolled double-blind trial of lipid-lowering strategies in patients with renal insufficiency: diet modification with or without fenofibrate. Clin Nephrol 2000 Feb; 53 (2): 140–6

    PubMed  CAS  Google Scholar 

  130. Keating GM, Ormrod D. Micronised fenofibrate: an updated review of its clinical efficacy in the management of dyslipidaemia. Drugs 2002; 62 (13): 1909–44

    Article  PubMed  CAS  Google Scholar 

  131. Farnier M, Salko T, Isaacsohn JL, et al. Effects of baseline level of triglycérides on changes in lipid levels from combined fluvastatin + fibrate (bezafibrate, fenofibrate, or gemfibrozil). Am J Cardiol 2003 Oct 1; 92 (7): 794–7

    Article  PubMed  CAS  Google Scholar 

  132. Stefanutti C, Bucci A, Di Giacomo S, et al. Efficacy, safety and tolerability of combined low-dose simvastatin-fenofibrate treatment in primary mixed hyperlipidaemia. Clin Drug Invest 2004; 24 (8): 465–77

    Article  CAS  Google Scholar 

  133. Liamis G, Kakafika A, Bairaktari E, et al. Combined treatment with fibrates and small doses of atorvastatin in patients with mixed hyperlipidemia. Curr Med Res Opin 2002; 18 (3): 125–8

    Article  PubMed  CAS  Google Scholar 

  134. McKenney JM, Farnier M, Lo K-W, et al. Safety and efficacy of long-term co-administration of fenofibrate and ezetimibe in patients with mixed hyperlipidemia. J Am Coll Cardiol 2006 Apr 18; 47 (8): 1584–7

    Article  PubMed  CAS  Google Scholar 

  135. Wysocki J, Belowski D, Kalina M, et al. Effects of micronized fenofibrate on insulin resistance in patients with metabolic syndrome. Int J Clin Pharmacol Ther 2004 Apr; 42 (4): 212–7

    PubMed  CAS  Google Scholar 

  136. Nieuwdorp M, Stroes ESG, Kastelein JJP, on behalf of the Fenofibrate/Metformin Study Group. Normalisation of metabolic syndrome using fenofibrate, metformin or their combination. Diabetes Obes Metab. In press

  137. Vega GL, Ma PTS, Cater NB, et al. Effects of adding fenofibrate (200 mg/day) to simvastatin (10 mg/day) in patients with combined hyperlipidemia and metabolic syndrome. Am J Cardiol 2003 Apr 15; 91: 956–60

    Article  PubMed  CAS  Google Scholar 

  138. Rosenson RS, Huskin AL, Wolfe DA. Fenofibrate markedly reduces postprandial dyslipidemia in metabolic syndrome patients [abstract no. 979-P]. Diabetes 2005 Jun; 54 Suppl. 1: A239

    Google Scholar 

  139. Filippatos TD, Kiortsis DN, Liberopoulos EN, et al. Effect of orlistat, micronised fenofibrate and their combination on metabolic parameters in overweight and obese patients with the metabolic syndrome: the FenOrli study. Curr Med Res Opin 2005 Dec; 21 (12): 1997–2006

    Article  PubMed  CAS  Google Scholar 

  140. McIvor ME. In combination with statins, fenofibrate, niacin and rosiglitazone effectively treat the atherogenic dyslipidemia of the metabolic syndrome [abstract no. 1084]. Circulation 2005 Oct 25; 112 (17 Suppl.): 209. Plus poster presented at the 78th Scientific Sessions of the American Heart Association; 2005 Nov 13–16; Dallas (TX)

    Google Scholar 

  141. Filippatos TD, Gazi IF, Liberopoulos EN, et al. The effect of orlistat and fenofibrate, alone or in combination, on small dense LDL and lipoprotein-associated phospholipase A2 in obese patients with metabolic syndrome. Atherosclerosis. Epub 2006 Aug 12

  142. Tan CE, Chew LS, Tai ES, et al. Benefits of micronised fenofibrate in type 2 diabetes mellitus subjects with good glycemic control. Atherosclerosis 2001 Feb 1; 154 (2): 469–74

    Article  PubMed  CAS  Google Scholar 

  143. The FIELD study investigators. Effects of long-term fenofibrate therapy on cardiovascular events in 9795 people with type 2 diabetes mellitus (the FIELD study): randomised controlled trial. Lancet 2005 Nov 26; 366 (9500): 1849–61

    Article  CAS  Google Scholar 

  144. Frost RJA, Otto C, Geiss HC, et al. Effects of atorvastatin versus fenofibrate on lipoprotein profiles, low-density lipoprotein subfraction distribution, and hemorheologic parameters in type 2 diabetes mellitus with mixed hyperlipoproteinemia. Am J Cardiol 2001 Jan 1; 87 (1): 44–8

    Article  PubMed  CAS  Google Scholar 

  145. Sarano N, Kozlov S, Tvorogova M, et al. Combined therapy with fluvastatin and fenofibrate in patients with hyperlipidaemia and non-insulin-dependent diabetes mellitus [abstract no. 111]. Heart 2000 Jun; 83 Suppl. II: 28

    Google Scholar 

  146. Durrington PN, Tuomilehto J, Hamann A, et al. Rosuvastatin and fenofibrate alone and in combination in type 2 diabetes patients with combined hyperlipidaemia. Diabetes Res Clin Pract 2004 May; 64 (2): 137–51

    Article  PubMed  CAS  Google Scholar 

  147. Muhlestein JB, May HT, Jensen JR, et al. The reduction of inflammatory biomarkers by statin, fibrate, and combination therapy among diabetic patients with mixed dyslipidemia: the DIACOR (Diabetes and Combined Lipid Therapy Regimen) study. J Am Coll Cardiol 2006 Jul 18; 48 (2): 396–401

    Article  PubMed  CAS  Google Scholar 

  148. Derosa G, Cicero AFG, Bertone G, et al. Comparison of fluvastatin + fenofibrate combination therapy and fluvastatin monotherapy in the treatment of combined hyperlipidemia, type 2 diabetes mellitus, and coronary heart disease: a 12-month, randomized, double-blind, controlled trial. Clin Ther 2004 Oct; 26 (10): 1599–607

    Article  PubMed  CAS  Google Scholar 

  149. Pearson RR, Thomas H, Jensen JR, et al. Triple-therapy with a statin, fibrate and ezetimibe safely allows more diabetic patients with mixed dyslipidemias to reach national cholesterol education program guidelines: an analysis of the DIACOR study [abstract no. 808-6 plus oral presentation]. 55th Annual Scientific Session of the American College of Cardiology; 2006 Mar 11–14; Atlanta (GA)

  150. Keech A, on behalf of the FIELD Study Investigators. Effects of long-term fenofibrate therapy on cardiovascular events among 9795 people with type 2 diabetes mellitus: the FIELD study, a randomised controlled trial [abstract no. We-S15:2]. Athero-sclerosis 2006 Jun; 7 (3 Suppl.): 342

    Google Scholar 

  151. Ansquer J-C, Foucher C, Rattier S, et al. Fenofibrate reduces progression to microalbuminuria over 3 years in a placebo-controlled study in type 2 diabetes: results from the Diabetes Atherosclerosis Intervention Study (DAIS). Am J Kidney Dis 2005 Mar; 45 (3): 485–93

    Article  CAS  Google Scholar 

  152. Hottelart C, El Esper N, Achard J-M, et al. Fenofibrate increases blood creatinine, but does not change the glomerular filtration rate in patients with mild renal insufficiency [in French]. Nephrologie 1999; 20 (1): 41–4

    PubMed  CAS  Google Scholar 

  153. Hottelart C, El Esper N, Rose F, et al. Fenofibrate increases creatininemia by increasing metabolic production of creatinine. Nephron 2002; 92 (3): 536–41

    Article  PubMed  CAS  Google Scholar 

  154. Graham DJ, Staffa JA, Shatin D, et al. Incidence of hospitalized rhabdomyolysis in patients treated with lipid-lowering drugs. J Am Med Asso 2004 Dec 1; 292 (21): 2585–90

    Article  CAS  Google Scholar 

  155. Barker BJ, Goodenough RR, Falko JM. Fenofibrate monotherapy induced rhabdomyolysis. Diabetes Care 2003 Aug; 26 (8): 2482–3

    Article  PubMed  Google Scholar 

  156. Jacob SS, Jacob S, Williams C, et al. Simvastatin, fenofibrate, and rhabdomyolysis. Diabetes Care 2005 May; 28 (5): 1258

    Article  PubMed  Google Scholar 

  157. Kursat S, Alici T, Colak HB. A case of rhabdomyolysis induced acute renal failure secondary to statin-fibrate-derivative combination and occult hypothyroidism. Clin Nephrol 2005 Nov; 64 (5): 391–3

    PubMed  CAS  Google Scholar 

  158. Ireland JHE, Eggert CH, Arendt CJ, et al. Rhabdomyolysis with cardiac involvement and acute renal failure in a patient taking rosuvastatin and fenofibrate. Ann Intern Med 2005 Jun 7; 142 (11): 949–50

    PubMed  Google Scholar 

  159. Ghosh B, Sengupta S, Bhattacharjee B, et al. Fenofibrate-induced myopathy. Neurol India 2004 Jun; 52 (2): 268–9

    PubMed  Google Scholar 

  160. Ledl M, Hohenecker J, Francesconi C, et al. Acute myopathy in a type 2 diabetic patient on combination therapy with metformin, fenofibrate and rosiglitazone. Diabetologia 2005 Oct; 48 (10): 1996–8

    Article  PubMed  CAS  Google Scholar 

  161. Alsheikh-Ali AA, Kuvin JT, Karas RH. Risk of adverse events with fibrates. Am J Cardiol 2004 Oct 1; 94 (7): 935–8

    Article  PubMed  CAS  Google Scholar 

  162. Jones PH, Davidson MH. Reporting rate of rhabdomyolysis with fenofibrate + statin versus gemfibrozil + any statin. Am J Cardiol 2005 Jan 1; 95 (1): 120–2

    Article  PubMed  CAS  Google Scholar 

  163. Goff Jr DC, Bertoni AG, Kramer H, et al. Dyslipidemia prevalence, treatment, and control in the Multi-Ethnic Study of Atherosclerosis (MESA): gender, ethnicity, and coronary artery calcium. Circulation 2006 Feb 7; 113: 647–56

    Article  PubMed  CAS  Google Scholar 

  164. Beaton SJ, Nag SS, Gunter MJ, et al. Adequacy of glycemic, lipid, and blood pressure management for patients with diabetes in a managed care setting. Diabetes Care 2004 Mar; 27 (3): 694–8

    Article  PubMed  Google Scholar 

  165. Davidson MH. Reducing residual risk for patients on statin therapy: potential role of combination therapy. Am J Cardiol 2005 Nov 7; 96 (9A): 3–13K

    Article  CAS  Google Scholar 

  166. Steiner G. A new perspective in the treatment of dyslipidemia: can fenofibrate offer unique benefits in the treatment of type 2 diabetes mellitus? Treat Endocrinol 2005; 4 (5): 311–7

    Article  PubMed  CAS  Google Scholar 

  167. Cholesterol Treatment Trialists’ (CTT) Collaborators. Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90 056 participants in 14 randomised trials of statins. Lancet 2005 Oct 8; 366 (9493): 1267–78

    Article  CAS  Google Scholar 

  168. Ballantyne CM, Herd A, Ferlic LL, et al. Influence of low HDL on progression of coronary artery disease and response to fluvastatin therapy. Circulation 1999 Feb 16; 99: 736–43

    Article  PubMed  CAS  Google Scholar 

  169. Woodman RJ, Chew GT, Watts GF. Mechanisms, significance and treatment of vascular dysfunction in type 2 diabetes mellitus: focus on lipid-regulating therapy. Drugs 2005; 65 (1): 31–74

    Article  PubMed  CAS  Google Scholar 

  170. Robins SJ, Collins D, Wittes JT, et al. Relation of gemfibrozil treatment and lipid levels with major coronary events: VA-HIT: a randomized controlled trial. JAMA 2001 Mar 28; 285 (12): 1585–91

    Article  PubMed  CAS  Google Scholar 

  171. Robins SJ. Cardiovascular disease with diabetes or the metabolic syndrome: should statins or fibrates be first line lipid therapy? Curr Opin Lipidol 2003 Dec; 14 (6): 575–83

    Article  PubMed  CAS  Google Scholar 

  172. Pyörälä K, Olsson AG, Pedersen TR, et al. Cholesterol lowering with simvastatin improves prognosis of diabetic patients with coronary heart disease: a subgroup analysis of the Scandinavian Simvastatin Survival Study. Diabetes Care 1997 Apr; 20 (4): 614–20

    Article  PubMed  Google Scholar 

  173. Haffner SM, Alexander CM, Cook TJ, et al. Reduced coronary events in simvastatin-treated patients with coronary heart disease and diabetes or impaired fasting glucose levels: subgroup analyses in the Scandinavian Simvastatin Survival Study. Arch Intern Med 1999 Dec 13/27; 159: 2661–7

    Article  PubMed  CAS  Google Scholar 

  174. Goldberg RB, Mellies MJ, Sacks FM, et al. Cardiovascular events and their reduction with pravastatin in diabetic and glucose-intolerant myocardial infarction survivors with average cholesterol levels: subgroup analyses in the Cholesterol and Recurrent Events (CARE) trial. Circulation 1998 Dec 8; 98: 2513–9

    Article  PubMed  CAS  Google Scholar 

  175. Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol-lowering with simvastatin in 5963 people with diabetes: a randomised placebo-controlled trial. Lancet 2003 Jun 14; 361 (9374): 2005–16

    Article  CAS  Google Scholar 

  176. Keech A, Colquhoun D, Best J, et al. Secondary prevention of cardiovascular events with long-term pravastatin in patients with diabetes or impaired fasting glucose: results from the LIPID trial. Diabetes Care 2003 Oct; 26 (10): 2713–21

    Article  PubMed  CAS  Google Scholar 

  177. Sever PS, Dahlöf B, Poulter NR, et al. Prevention of coronary and stroke events with atorvastatin in hypertensive patients who have average or lower-than-average cholesterol concentrations, in the Anglo-Scandinavian Cardiac Outcomes Trial — Lipid Lowering Arm (ASCOT-LLA): a multicentre randomised controlled trial. Lancet 2003 Apr 5; 361 (9364): 1149–58

    Article  PubMed  CAS  Google Scholar 

  178. Colhoun HM, Betteridge DJ, Durrington PN, et al. Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): multicentre randomised placebo-controlled trial. Lancet 2004 Aug 21; 364 (9435): 685–96

    Article  PubMed  CAS  Google Scholar 

  179. Knopp RH, D’Emden M, Smilde JG, et al. Efficacy and safety of atorvastatin in the prevention of cardiovascular end points in subjects with type 2 diabetes: the Atorvastatin Study for Prevention of Coronary Heart Disease Endpoints in Non-insulin-dependent diabetes mellitus (ASPEN). Diabetes Care 2006 Jul; 29 (7): 1478–85

    Article  PubMed  CAS  Google Scholar 

  180. Wanner C, Krane V, März W, et al. Atorvastatin in patients with type 2 diabetes mellitus undergoing haemodialysis. N Engl J Med 2005 Jul 21; 353 (3): 238–48

    Article  PubMed  CAS  Google Scholar 

  181. Tenkanen L, Mänttäri M, Kovanen PT, et al. Gemfibrozil in the treatment of dyslipidemia: an 18-year mortality follow-up of the Helsinki Heart Study. Arch Intern Med 2006 Apr 10; 166: 743–8

    Article  PubMed  CAS  Google Scholar 

  182. Tenenbaum A, Fisman EZ, Boyko V, et al. Attenuation of progression of insulin resistance in patients with coronary artery disease by bezafibrate. Arch Int Med 2006 Apr 10; 166: 737–41

    Article  CAS  Google Scholar 

  183. Tenenbaum A, Motro M, Fisman EZ, et al. Bezafibrate for the secondary prevention of myocardial infarction in patients with metabolic syndrome. Arch Intern Med 2005 May 23; 165: 1154–60

    Article  PubMed  CAS  Google Scholar 

  184. Rubins HB, Robins SJ, Collins D, et al. Diabetes, plasma insulin, and cardiovascular disease: subgroup analysis from the Department of Veterans Affairs High-Density Lipoprotein Intervention Trial (VA-HIT). Arch Intern Med 2002 Dec 9/23; 162: 2597–604

    Article  PubMed  CAS  Google Scholar 

  185. UK Prospective Diabetes Study (UKPDS) Group. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet 1998 Sep 12; 352: 854–65

    Article  Google Scholar 

  186. Colhoun H. After FIELD: should fibrates be used to prevent cardiovascular disease in diabetes? Lancet 2005 Nov 26; 366 (9500): 1829–31

    Article  PubMed  Google Scholar 

  187. ClinicalTrials.gov. Strategies to reduce cardiovascular disease risk in individuals with diabetes [online]. Available from URL: http://www.clinicaltrials.gov/ct/gui/show/NCT000006207order=2 [Accessed 2006 Feb 4]

  188. Smith Jr SC, Allen J, Blair SN, et al. AHA/ACC guidelines for secondary prevention for patients with coronary and other atherosclerotic vascular disease: 2006 update. Circulation 2006 May 16; 113: 2363–72

    Article  PubMed  Google Scholar 

  189. De Backer G, Ambrosioni E, Borch-Johnsen K, et al. European guidelines on cardiovascular disease prevention in clinical practice: third joint task force of European and other societies on cardiovascular disease prevention in clinical practice (constituted by representatives of eight societies and by invited experts). Atherosclerosis 2004 Apr; 173 (2): 381–91

    PubMed  Google Scholar 

  190. Prueksaritanont T, Tang C, Qiu Y, et al. Effects of fibrates on metabolism of statins in human hepatocytes. Drug Metab Dispos 2002; 30 (11): 1280–7

    Article  PubMed  CAS  Google Scholar 

  191. Prueksaritanont T, Zhao JJ, Ma B, et al. Mechanistic studies on metabolic interactions between gemfibrozil and statins. J Pharmacol Exp Ther 2002; 301 (3): 1042–51

    Article  PubMed  CAS  Google Scholar 

  192. Wang J-S, Neuvonen M, Wen X, et al. Gemfibrozil inhibits CYP2C8-mediated cerivastatin metabolism in human liver microsomes. Drug Metab Dispos 2002; 30 (12): 1352–6

    Article  PubMed  Google Scholar 

  193. Farnier M. Combination therapy with an HMG-CoA reductase inhibitor and a fibric acid derivative: a critical review of potential benefits and drawbacks. Am J Cardiovasc Drugs 2003 Jan; 3 (3): 169–78

    Article  PubMed  CAS  Google Scholar 

  194. Merck/Schering-Plough Pharmaceuticals. Zetia® (ezetimibe) tablets: prescribing information [online]. Available from URL: http://www.fda.gov [Accessed 2006 May 10]

Download references

Author information

Authors and Affiliations

  1. Wolters Kluwer Health / Adis, 41 Centorian Drive, Private Bag 65901, Mairangi Bay, Auckland, 1311, New Zealand

    Gillian M. Keating & Katherine F. Croom

Authors
  1. Gillian M. Keating
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Katherine F. Croom
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Gillian M. Keating.

Additional information

Various sections of the manuscript reviewed by: M. Farnier, Point Médical, Rond Point de la Nation, Dijon, France; P. Gervois, Laboratoire de Biochimie, Faculté des Sciences Pharmaceutiques et Biologiques 3, Lille, France; P.H. Jones, Methodist DeBakey Heart Center, Baylor College of Medicine, Houston, Texas, USA; D.N. Kiortsis, Medical School, University of Ioannina, Ioannina, Greece; V. Melenovsky, Department of Cardiology, IKEM, Prague, Czech Republic; K.G. Parhofer, University of Munich, Klinikum Grosshadern, Munich, Germany; G.F. Watts, School of Medicine and Pharmacology, University of Western Australia, Royal Perth Hospital, Perth, Western Australia, Australia.

Data Selection

Sources: Medical literature published in any language since 1980 on ‘fenofibrate’, identified using MEDLINE and EMBASE, supplemented by AdisBase (a proprietary database of Adis International). Additional references were identified from the reference lists of published articles. Bibliographical information, including contributory unpublished data, was also requested from the company developing the drug.

Search strategy: MEDLINE, EMBASE and AdisBase search terms were ‘fenofibrate’ or ‘fibric acid derivatives’. Searches were last updated 18 December 2006.

Selection: Studies in patients with primary dyslipidaemia, the metabolic syndrome or type 2 diabetes mellitus who received fenofibrate. Inclusion of studies was based mainly on the methods section of the trials. When available, large, well controlled trials with appropriate statistical methodology were preferred. Relevant pharmacodynamic and pharmacokinetic data are also included.

Index terms: Fenofibrate, dyslipidaemia, metabolic syndrome, type 2 diabetes mellitus, pharmacodynamics, pharmacokinetics, therapeutic use.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Keating, G.M., Croom, K.F. Fenofibrate. Drugs 67, 121–153 (2007). https://doi.org/10.2165/00003495-200767010-00013

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00003495-200767010-00013

Keywords

Search

Navigation