Advertisement

Fibrate Therapy: Impact on Dyslipidemia and Cardiovascular Events in Diabetic Patients

  • Eliot A. Brinton
Chapter
Part of the Contemporary Diabetes book series (CDI)

Abstract

Coronary heart disease (CHD) and ischemic stroke are both primarily due to atherosclerosis. Due to their common pathophysiology, they are often considered together under the term of cardiovascular disease (CVD). CVD is the leading cause of morbidity and mortality in the United States [1], with over three-quarters of a million new cases of CHD and a similar number of strokes each year. Lowering of levels of low-density lipoprotein-cholesterol (LDL-C) with statin monotherapy is well proven to reduce CVD events by about 20–50 % [2]. Importantly, the degree of risk reduction is proportional to the degree of LDL-C decrease—21 % CVD event decrease per 39 mg/dL (1 mmol/L) LDL-C decrease [2]—and an identical 21 % decrease per 39 mg/dL decrease is seen in patients with diabetes mellitus type 2 (DM-2) [3]. Due to higher overall CVD risk in DM-2 (other risk factors being equal), the absolute risk reduction is greater than in those without DM-2, and only 24 patients with DM-2 would need a statin-induced 39 mg/dL decrease in LDL-C for 5 years to prevent one major CVD event. Although such treatment is clinically useful and generally cost-effective, it is important to note that the majority of CVD events, roughly 50–80 %, still occur despite statin treatment [4–7]. Of course, there is considerable interest in learning how to reduce this large residual risk. This is especially true in patients with high CVD risk due to strong risk factors such as DM-2, among whom the 50–80 % residual CVD risk is thus larger in absolute terms.

Keywords

Cholesteryl Ester Transfer Protein Lecithin Cholesterol Acyl Transferase Statin Monotherapy Fibrate Therapy Fibrate Treatment 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. 1.
    Roger VL, Go AS, Lloyd-Jones DM, et al. Heart disease and stroke statistics—2012 update. Circulation 2012;125(22):e1002.Google Scholar
  2. 2.
    Baigent C, Keech A, Kearney PM, et al. Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins. Lancet. 2005;366:1267–78.PubMedCrossRefGoogle Scholar
  3. 3.
    Kearney PM, Blackwell L, Collins R, et al. Efficacy of cholesterol-lowering therapy in 18,686 people with diabetes in 14 randomised trials of statins: a meta-analysis. Lancet. 2008;371:117–25.PubMedCrossRefGoogle Scholar
  4. 4.
    Scandinavian Simvastatin Survival Study Group. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet. 1994;344: 1383–9.Google Scholar
  5. 5.
    Downs JR, Clearfield M, Weis S, et al. Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels. JAMA. 1998;279:1615–22.PubMedCrossRefGoogle Scholar
  6. 6.
    Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of antioxidant vitamin supplementation in 20536 high-risk individuals: a randomised placebo-controlled trial. Lancet. 2002;360:23–33.CrossRefGoogle Scholar
  7. 7.
    Marschner IC, Colquhoun D, Simes RJ, et al. Long-term risk stratification for survivors of acute coronary syndromes. Results from the Long-term Intervention with Pravastatin in Ischemic Disease (LIPID) Study. LIPID Study Investigators. J Am Coll Cardiol. 2001;38:56–63.PubMedCrossRefGoogle Scholar
  8. 8.
    Asztalos BF, Batista M, Horvath KV, et al. Change in alpha1 HDL concentration predicts progression in coronary artery stenosis. Arterioscler Thromb Vasc Biol. 2003;23:847–52.PubMedCrossRefGoogle Scholar
  9. 9.
    Ballantyne CM, Herd JA, Ferlic LL, et al. Influence of low HDL on progression of coronary artery disease and response to fluvastatin therapy. Circulation. 1999;99:736–43.PubMedCrossRefGoogle Scholar
  10. 10.
    Johnsen SH, Mathiesen EB, Fosse E, et al. Elevated high-density lipoprotein cholesterol levels are protective against plaque progression: a follow-up study of 1952 persons with carotid atherosclerosis the Tromso study. Circulation. 2005;112:498–504.PubMedCrossRefGoogle Scholar
  11. 11.
    Despres JP, Lemieux I, Dagenais GR, Cantin B, Lamarche B. HDL-cholesterol as a marker of coronary heart disease risk: the Quebec cardiovascular study. Atherosclerosis. 2000;153:263–72.PubMedCrossRefGoogle Scholar
  12. 12.
    Grant RW, Meigs JB. Prevalence and treatment of low HDL cholesterol among primary care patients with type 2 diabetes: an unmet challenge for cardiovascular risk reduction. Diabetes Care. 2007;30:479–84.PubMedCrossRefGoogle Scholar
  13. 13.
    Bruckert E, Baccara-Dinet M, McCoy F, Chapman J. High prevalence of low HDL-cholesterol in a pan-European survey of 8545 dyslipidaemic patients. Curr Med Res Opin. 2005;21:1927–34.PubMedCrossRefGoogle Scholar
  14. 14.
    Barter P, Gotto AM, LaRosa JC, et al. HDL cholesterol, very low levels of LDL cholesterol, and cardiovascular events. N Engl J Med. 2007;357:1301–10.PubMedCrossRefGoogle Scholar
  15. 15.
    Di Angelantonio E, Sarwar N, Perry P, et al. Major lipids, apolipoproteins, and risk of vascular disease. JAMA. 2009;302:1993–2000.PubMedCrossRefGoogle Scholar
  16. 16.
    Boden WE, Probstfield JL, Anderson T, et al. Niacin in patients with low HDL cholesterol levels receiving intensive statin therapy. N Engl J Med. 2011;365: 2255–67.PubMedCrossRefGoogle Scholar
  17. 17.
    Khera AV, Cuchel M, de la Llera-Moya M, et al. Cholesterol efflux capacity, high-density lipoprotein function, and atherosclerosis. N Engl J Med. 2011; 364:127–35.PubMedCentralPubMedCrossRefGoogle Scholar
  18. 18.
    Cavigiolio G, Shao B, Geier EG, Ren G, Heinecke JW, Oda MN. The interplay between size, morphology, stability, and functionality of high-density lipoprotein subclasses. Biochemistry. 2008;47:4770–9.PubMedCentralPubMedCrossRefGoogle Scholar
  19. 19.
    von Eckardstein A. Implications of torcetrapib failure for the future of HDL therapy: is HDL-cholesterol the right target? Expert Rev Cardiovasc Ther. 2010;8: 345–58.CrossRefGoogle Scholar
  20. 20.
    Hokanson JE, Austin MA. Plasma triglyceride level is a risk factor for cardiovascular disease independent of high-density lipoprotein cholesterol level: a meta-analysis of population-based prospective studies. J Cardiovasc Risk. 1996;3:213–9.PubMedCrossRefGoogle Scholar
  21. 21.
    Hopkins PN, Wu LL, Hunt SC, Brinton EA. Plasma triglycerides and type III hyperlipidemia are independently associated with premature familial coronary artery disease. J Am Coll Cardiol. 2005;45: 1003–12.PubMedCrossRefGoogle Scholar
  22. 22.
    Yuan G, Al-Shali KZ, Hegele RA. Hypertriglyceridemia: its etiology, effects and treatment. CMAJ. 2007;176:1113–20.PubMedCentralPubMedCrossRefGoogle Scholar
  23. 23.
    Austin MA, Hokanson JE, Edwards KL. Hypertriglyceridemia as a cardiovascular risk factor. Am J Cardiol. 1998;81:7B–12.PubMedCrossRefGoogle Scholar
  24. 24.
    Sacks FM, Tonkin AM, Shepherd J, et al. Effect of pravastatin on coronary disease events in subgroups defined by coronary risk factors: the Prospective Pravastatin Pooling Project. Circulation. 2000;102: 1893–900.PubMedCrossRefGoogle Scholar
  25. 25.
    Sacks FM, Alaupovic P, Moye LA, et al. VLDL, apolipoproteins B, CIII, and E, and risk of recurrent coronary events in the Cholesterol and Recurrent Events (CARE) trial. Circulation. 2000;102:1886–92.PubMedCrossRefGoogle Scholar
  26. 26.
    Miller M, Cannon CP, Murphy SA, Qin J, Ray KK, Braunwald E. Impact of triglyceride levels beyond low-density lipoprotein cholesterol after acute coronary syndrome in the PROVE IT-TIMI 22 trial. J Am Coll Cardiol. 2008;51:724–30.PubMedCrossRefGoogle Scholar
  27. 27.
    Drexel H, Aczel S, Marte T, Vonbank A, Saely CH. Factors predicting cardiovascular events in statin-treated diabetic and non-diabetic patients with coronary atherosclerosis. Atherosclerosis. 2010;208:484–9.PubMedCrossRefGoogle Scholar
  28. 28.
    Langsted A, Freiberg JJ, Tybjaerg-Hansen A, Schnohr P, Jensen GB, Nordestgaard BG. Nonfasting cholesterol and triglycerides and association with risk of myocardial infarction and total mortality: the Copenhagen City Heart Study with 31 years of follow-up. J Intern Med. 2011;270:65–75.PubMedCrossRefGoogle Scholar
  29. 29.
    Langsted A, Nordestgaard BG. Nonfasting lipids, lipoproteins, and apolipoproteins in individuals with and without diabetes: 58 434 individuals from the Copenhagen General Population Study. Clin Chem. 2011;57:482–9.PubMedCrossRefGoogle Scholar
  30. 30.
    Rader DJ. Mechanisms of disease: HDL metabolism as a target for novel therapies. Nat Clin Pract Cardiovasc Med. 2007;4:102–9.PubMedCrossRefGoogle Scholar
  31. 31.
    Vergeer M, Holleboom AG, Kastelein JJ, Kuivenhoven JA. The HDL hypothesis: does high-density lipoprotein protect from atherosclerosis? J Lipid Res. 2010;51:2058–73.PubMedCrossRefGoogle Scholar
  32. 32.
    Brewer Jr HB. Clinical review: the evolving role of HDL in the treatment of high-risk patients with cardiovascular disease. J Clin Endocrinol Metab. 2011;96:1246–57.PubMedCrossRefGoogle Scholar
  33. 33.
    Navab M, Reddy ST, Van Lenten BJ, Fogelman AM. HDL and cardiovascular disease: atherogenic and atheroprotective mechanisms. Nat Rev Cardiol. 2011;8: 222–32.PubMedCrossRefGoogle Scholar
  34. 34.
    Ginsberg HN. New perspectives on atherogenesis: role of abnormal triglyceride-rich lipoprotein metabolism. Circulation. 2002;106:2137–42.PubMedCrossRefGoogle Scholar
  35. 35.
    Wang L, Gill R, Pedersen TL, Higgins LJ, Newman JW, Rutledge JC. Triglyceride-rich lipoprotein lipolysis releases neutral and oxidized FFAs that induce endothelial cell inflammation. J Lipid Res. 2009;50:204–13.PubMedCrossRefGoogle Scholar
  36. 36.
    Austin MA, King MC, Vranizan KM, Krauss RM. Atherogenic lipoprotein phenotype. A proposed genetic marker for coronary heart disease risk. Circulation. 1990;82:495–506.PubMedCrossRefGoogle Scholar
  37. 37.
    Brinton EA, Eisenberg S, Breslow JL. Increased apo A-I and apo A-II fractional catabolic rate in patients with low high density lipoprotein-cholesterol levels with or without hypertriglyceridemia. J Clin Invest. 1991;87:536–44.PubMedCentralPubMedCrossRefGoogle Scholar
  38. 38.
    Brinton EA, Eisenberg S, Breslow JL. Human HDL cholesterol levels are determined by apoA-I fractional catabolic rate, which correlates inversely with estimates of HDL particle size. Effects of gender, hepatic and lipoprotein lipases, triglyceride and insulin levels, and body fat distribution. Arterioscler Thromb. 1994;14:707–20.PubMedCrossRefGoogle Scholar
  39. 39.
    Taskinen MR. Diabetic dyslipidaemia: from basic research to clinical practice. Diabetologia. 2003;46: 733–49.PubMedCrossRefGoogle Scholar
  40. 40.
    Lamarche B, Tchernof A, Moorjani S, et al. Small, dense low-density lipoprotein particles as a predictor of the risk of ischemic heart disease in men. Prospective results from the Quebec Cardiovascular Study. Circulation. 1997;95:69–75.PubMedCrossRefGoogle Scholar
  41. 41.
    St-Pierre AC, Ruel IL, Cantin B, et al. Comparison of various electrophoretic characteristics of LDL particles and their relationship to the risk of ischemic heart disease. Circulation. 2001;104:2295–9.PubMedCrossRefGoogle Scholar
  42. 42.
    Hirano T, Ito Y, Koba S, et al. Clinical significance of small dense low-density lipoprotein cholesterol levels determined by the simple precipitation method. Arterioscler Thromb Vasc Biol. 2004;24:558–63.PubMedCrossRefGoogle Scholar
  43. 43.
    Rizzo M, Pernice V, Frasheri A, et al. Small, dense low-density lipoproteins (LDL) are predictors of cardio- and cerebro-vascular events in subjects with the metabolic syndrome. Clin Endocrinol (Oxf). 2009;70:870–5.CrossRefGoogle Scholar
  44. 44.
    Taskinen MR. LDL-cholesterol, HDL-cholesterol or triglycerides–which is the culprit? Diabetes Res Clin Pract. 2003;61 Suppl 1:S19–26.PubMedCrossRefGoogle Scholar
  45. 45.
    Abourbih S, Filion KB, Joseph L, et al. Effect of fibrates on lipid profiles and cardiovascular outcomes: a systematic review. Am J Med. 2009;122:962 e1–8.CrossRefGoogle Scholar
  46. 46.
    Jun M, Foote C, Lv J, et al. Effects of fibrates on cardiovascular outcomes: a systematic review and meta-analysis. Lancet. 2010;375:1875–84.PubMedCrossRefGoogle Scholar
  47. 47.
    Vakkilainen J, Steiner G, Ansquer JC, et al. Relationships between low-density lipoprotein particle size, plasma lipoproteins, and progression of coronary artery disease: the Diabetes Atherosclerosis Intervention Study (DAIS). Circulation. 2003;107: 1733–7.PubMedCrossRefGoogle Scholar
  48. 48.
    Hiukka A, Leinonen E, Jauhiainen M, et al. Long-term effects of fenofibrate on VLDL and HDL subspecies in participants with type 2 diabetes mellitus. Diabetologia. 2007;50:2067–75.PubMedCrossRefGoogle Scholar
  49. 49.
    Franceschini G, Calabresi L, Colombo C, Favari E, Bernini F, Sirtori CR. Effects of fenofibrate and simvastatin on HDL-related biomarkers in low-HDL patients. Atherosclerosis. 2007;195:385–91.PubMedCrossRefGoogle Scholar
  50. 50.
    Ginsberg HN. Insulin resistance and cardiovascular disease. J Clin Invest. 2000;106:453–8.PubMedCentralPubMedCrossRefGoogle Scholar
  51. 51.
    Atmeh RF, Shepherd J, Packard CJ. Subpopulations of apolipoprotein A-I in human high-density lipoproteins. Their metabolic properties and response to drug therapy. Biochim Biophys Acta. 1983;751:175–88.PubMedCrossRefGoogle Scholar
  52. 52.
    Toth PP, Thakker KM, Jiang P, Padley RJ. Niacin extended-release/simvastatin combination therapy produces larger favorable changes in high-density lipoprotein particles than atorvastatin monotherapy. Vasc Health Risk Manag. 2012;8:39–44.PubMedCentralPubMedCrossRefGoogle Scholar
  53. 53.
    Otvos JD, Collins D, Freedman DS, et al. Low-density lipoprotein and high-density lipoprotein particle subclasses predict coronary events and are favorably changed by gemfibrozil therapy in the Veterans Affairs High-Density Lipoprotein Intervention Trial. Circulation. 2006;113:1556–63.PubMedCrossRefGoogle Scholar
  54. 54.
    Tenkanen L, Manttari M, Kovanen PT, Virkkunen H, Manninen V. Gemfibrozil in the treatment of dyslipidemia: an 18-year mortality follow-up of the Helsinki Heart Study. Arch Intern Med. 2006;166:743–8.PubMedCrossRefGoogle Scholar
  55. 55.
    Keech A, Simes RJ, Barter P, et al. 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;366: 1849–61.PubMedCrossRefGoogle Scholar
  56. 56.
    Ginsberg HN, Elam MB, Lovato LC, et al. Effects of combination lipid therapy in type 2 diabetes mellitus. N Engl J Med. 2010;362:1563–74.PubMedCrossRefGoogle Scholar
  57. 57.
    Manninen V, Elo MO, Frick MH, et al. Lipid alterations and decline in the incidence of coronary heart disease in the Helsinki Heart Study. JAMA. 1988;260:641–51.PubMedCrossRefGoogle Scholar
  58. 58.
    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;3:169–78.PubMedCrossRefGoogle Scholar
  59. 59.
    Brinton EA. Does the addition of fibrates to statin therapy have a favorable risk to benefit ratio? Curr Atheroscler Rep. 2008;10:25–32.PubMedCrossRefGoogle Scholar
  60. 60.
    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;48:396–401.PubMedCrossRefGoogle Scholar
  61. 61.
    Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). Executive summary of the 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). JAMA. 2001;285:2486–97.CrossRefGoogle Scholar
  62. 62.
    van Eck M, Bos IS, Kaminski WE, et al. Leukocyte ABCA1 controls susceptibility to atherosclerosis and macrophage recruitment into tissues. Proc Natl Acad Sci USA. 2002;99:6298–303.PubMedCrossRefGoogle Scholar
  63. 63.
    Miyazaki T, Shimada K, Miyauchi K, et al. Effects of fenofibrate on lipid profiles, cholesterol ester transfer activity, and in-stent intimal hyperplasia in patients after elective coronary stenting. Lipids Health Dis. 2010;9:122.PubMedCentralPubMedCrossRefGoogle Scholar
  64. 64.
    Navab M, Yu R, Gharavi N, et al. High-density lipoprotein: antioxidant and anti-inflammatory properties. Curr Atheroscler Rep. 2007;9:244–8.PubMedCrossRefGoogle Scholar
  65. 65.
    Schaefer EJ, McNamara JR, Asztalos BF, et al. Effects of atorvastatin versus other statins on fasting and postprandial C-reactive protein and lipoprotein-associated phospholipase A2 in patients with coronary heart disease versus control subjects. Am J Cardiol. 2005;95:1025–32.PubMedCrossRefGoogle Scholar
  66. 66.
    Ridker PM, Cook N. Clinical usefulness of very high and very low levels of C-reactive protein across the full range of Framingham Risk Scores. Circulation. 2004;109:1955–9.PubMedCrossRefGoogle Scholar
  67. 67.
    Albert MA, Danielson E, Rifai N, Ridker PM. Effect of statin therapy on C-reactive protein levels: the pravastatin inflammation/CRP evaluation (PRINCE): a randomized trial and cohort study. JAMA. 2001;286:64–70.PubMedCrossRefGoogle Scholar
  68. 68.
    Elkeles R. Fibrates: old drugs with a new role in type 2 diabetes prevention? Br J Diabetes Vasc Dis. 2011;11:4–9.CrossRefGoogle Scholar
  69. 69.
    Tenenbaum A, Fisman EZ, Boyko V, et al. Attenuation of progression of insulin resistance in patients with coronary artery disease by bezafibrate. Arch Intern Med. 2006;166:737–41.PubMedCrossRefGoogle Scholar
  70. 70.
    Steiner G. Effect of fenofibrate on progression of coronary-artery disease in type 2 diabetes: the Diabetes Atherosclerosis Intervention Study, a randomised study. Lancet 2001;357:905–10.Google Scholar
  71. 71.
    Emmerich KH, Poritis N, Stelmane I, et al. Efficacy and safety of etofibrate in patients with non-proliferative diabetic retinopathy. Klin Monbl Augenheilkd. 2009;226:561–7.PubMedCrossRefGoogle Scholar
  72. 72.
    Keech AC, Mitchell P, Summanen PA, et al. Effect of fenofibrate on the need for laser treatment for diabetic retinopathy (FIELD study): a randomised controlled trial. Lancet. 2007;370:1687–97.PubMedCrossRefGoogle Scholar
  73. 73.
    Davis TM, Ting R, Best JD, et al. Effects of fenofibrate on renal function in patients with type 2 diabetes mellitus: the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) Study. Diabetologia. 2011;54:280–90.PubMedCrossRefGoogle Scholar
  74. 74.
    Rajamani K, Colman PG, Li LP, et al. Effect of fenofibrate on amputation events in people with type 2 diabetes mellitus (FIELD study): a prespecified analysis of a randomised controlled trial. Lancet. 2009; 373:1780–8.PubMedCentralPubMedCrossRefGoogle Scholar
  75. 75.
    Elkeles RS, Diamond JR, Poulter C, et al. Cardiovascular outcomes in type 2 diabetes. A double-blind placebo-controlled study of bezafibrate: the St. Mary’s, Ealing, Northwick Park Diabetes Cardiovascular Disease Prevention (SENDCAP) Study. Diabetes Care. 1998;21:641–8.PubMedCrossRefGoogle Scholar
  76. 76.
    Hiukka A, Westerbacka J, Leinonen ES, et al. Long-term effects of fenofibrate on carotid intima-media thickness and augmentation index in subjects with type 2 diabetes mellitus. J Am Coll Cardiol. 2008;52: 2190–7.PubMedCrossRefGoogle Scholar
  77. 77.
    Zhu S, Su G, Meng QH. Inhibitory effects of micronized fenofibrate on carotid atherosclerosis in patients with essential hypertension. Clin Chem. 2006;52: 2036–42.PubMedCrossRefGoogle Scholar
  78. 78.
    Ericsson CG, Hamsten A, Nilsson J, Grip L, Svane B, de Faire U. Angiographic assessment of effects of bezafibrate on progression of coronary artery disease in young male postinfarction patients. Lancet. 1996; 347:849–53.PubMedCrossRefGoogle Scholar
  79. 79.
    Frick MH, Syvanne M, Nieminen MS, et al. Prevention of the angiographic progression of coronary and vein-graft atherosclerosis by gemfibrozil after coronary bypass surgery in men with low levels of HDL cholesterol. Lopid Coronary Angiography Trial (LOCAT) Study Group. Circulation. 1997;96: 2137–43.PubMedCrossRefGoogle Scholar
  80. 80.
    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;162:2597–604.PubMedCrossRefGoogle Scholar
  81. 81.
    Robins SJ, Rubins HB, Faas FH, et al. Insulin resistance and cardiovascular events with low HDL cholesterol: the Veterans Affairs HDL Intervention Trial (VA-HIT). Diabetes Care. 2003;26:1513–7.PubMedCrossRefGoogle Scholar
  82. 82.
    FIELD Study Investigators. The need for a large-scale trial of fibrate therapy in diabetes: the rationale and design of the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study. [ISRCTN64783481]. Cardiovasc Diabetol. 2004;3:9.CrossRefGoogle Scholar
  83. 83.
    Manninen V, Tenkanen L, Koskinen P, et al. Joint effects of serum triglyceride and LDL cholesterol and HDL cholesterol concentrations on coronary heart disease risk in the Helsinki Heart Study. Implications for treatment. Circulation. 1992;85:37–45.PubMedCrossRefGoogle Scholar
  84. 84.
    Scott R, O’Brien R, Fulcher G, et al. Effects of fenofibrate treatment on cardiovascular disease risk in 9,795 individuals with type 2 diabetes and various components of the metabolic syndrome: the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study. Diabetes Care. 2009;32:493–8.PubMedCrossRefGoogle Scholar
  85. 85.
    Lee M, Saver JL, Towfighi A, Chow J, Ovbiagele B. Efficacy of fibrates for cardiovascular risk reduction in persons with atherogenic dyslipidemia: a meta-analysis. Atherosclerosis. 2011;217:492–8.PubMedCrossRefGoogle Scholar
  86. 86.
    Baigent C, Blackwell L, Emberson J, et al. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet. 2010;376: 1670–81.PubMedCrossRefGoogle Scholar
  87. 87.
    Barter PJ, Rye KA. Cardioprotective properties of fibrates: which fibrate, which patients, what mechanism? Circulation. 2006;113:1553–5.PubMedCrossRefGoogle Scholar
  88. 88.
    Davidson MH, Armani A, McKenney JM, Jacobson TA. Safety considerations with fibrate therapy. Am J Cardiol. 2007;99:3C–18.PubMedCrossRefGoogle Scholar
  89. 89.
    Jones PH, Davidson MH. Reporting rate of rhabdomyolysis with fenofibrate + statin versus gemfibrozil + any statin. Am J Cardiol. 2005;95:120–2.PubMedCrossRefGoogle Scholar
  90. 90.
    Chapman MJ, Ginsberg HN, Amarenco P, et al. Triglyceride-rich lipoproteins and high-density lipoprotein cholesterol in patients at high risk of cardiovascular disease: evidence and guidance for management. Eur Heart J. 2011;32:1345–61.PubMedCrossRefGoogle Scholar
  91. 91.
    Ansquer JC, Foucher C, Rattier S, Taskinen MR, Steiner G. 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;45:485–93.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  1. 1.Cardiovascular GeneticsUniversity of Utah School of MedicineSalt Lake CityUSA
  2. 2.Utah Lipid CenterSalt Lake CityUSA
  3. 3.Utah Foundation for Biomedical ResearchSalt Lake CityUSA

Personalised recommendations