Role of fibrates in cardiovascular disease prevention, the ACCORD-Lipid perspective

Purpose of review To examine the results of the Action to Control Cardiovascular Risk in Diabetes (ACCORD)-Lipid trial, particularly the subgroup analyses. It is important, when a study fails to meet its overall primary endpoint, to ensure that interpretation of the results include analyses of subgroups that might benefit from the treatment tested. The goal of this review, therefore, is to provide insight and advice to physicians and healthcare workers treating patients similar to those enrolled in ACCORD. Recent findings The recently published results of ACCORD-Lipid trial will be presented upon the background of previous trials that have tested the ability of fibrates to lower cardiovascular risk. Summary Although ACCORD-Lipid trial did not provide support for the general addition of fenofibrate to statin-treated patients with type 2 diabetes mellitus (T2DM), it added significantly to the results from fibrate monotherapy trials indicative of benefit from such treatment in subgroups of patients who present with significant dyslipidemia. In particular, ACCORD-Lipid trial, in our view, supports the addition of fenofibrate to statin therapy in patients with T2DM and optimal low-density lipoprotein cholesterol levels but persistent, significant hypertriglyceridemia (>200 mg/dl) and low high-density lipoprotein cholesterol levels (<35–40 mg/dl).

[1]  M. Clearfield Combination Lipid Therapy in Type 2 Diabetes , 2011, Current atherosclerosis reports.

[2]  D. Grobbee,et al.  Effects of fibrates on cardiovascular outcomes: a systematic review and meta-analysis , 2010, The Lancet.

[3]  D. Rader,et al.  The effect of PPAR-alpha agonism on apolipoprotein metabolism in humans. , 2010, Atherosclerosis.

[4]  John B Buse,et al.  Effects of combination lipid therapy in type 2 diabetes mellitus. , 2010, The New England journal of medicine.

[5]  Kevin A Peterson,et al.  Effects of Intensive Blood-Pressure Control in Type 2 Diabetes Mellitus , 2011 .

[6]  A. Keech,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 , 2008, Diabetes Care.

[7]  S. Schinner,et al.  Effects of Intensive Glucose Lowering in Type 2 Diabetes , 2009 .

[8]  D. Goff,et al.  Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial: design and methods. , 2007, The American journal of cardiology.

[9]  J. Hsia,et al.  Effect of Lowering LDL Cholesterol Substantially Below Currently Recommended Levels in Patients With Coronary Heart Disease and Diabetes , 2006, Diabetes Care.

[10]  P Glasziou,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 , 2005, The Lancet.

[11]  D. Tanné,et al.  Bezafibrate for the secondary prevention of myocardial infarction in patients with metabolic syndrome. , 2005, Archives of internal medicine.

[12]  S. Grundy,et al.  Effectiveness and tolerability of simvastatin plus fenofibrate for combined hyperlipidemia (the SAFARI trial). , 2005, The American journal of cardiology.

[13]  John H Fuller,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 , 2004, The Lancet.

[14]  Henrik Vestergaard,et al.  The independent effect of type 2 diabetes mellitus on ischemic heart disease, stroke, and death: a population-based study of 13,000 men and women with 20 years of follow-up. , 2004, Archives of internal medicine.

[15]  Sarah Parish,et al.  MRC/BHF Heart Protection Study of cholesterol-lowering with simvastatin in 5963 people with diabetes: a randomised placebo-controlled trial , 2003, The Lancet.

[16]  James W. Anderson,et al.  Insulin resistance and cardiovascular events with low HDL cholesterol: the Veterans Affairs HDL Intervention Trial (VA-HIT). , 2003, Diabetes care.

[17]  W. März,et al.  Risk for myopathy with statin therapy in high-risk patients. , 2003, Archives of internal medicine.

[18]  G. Watts,et al.  Differential regulation of lipoprotein kinetics by atorvastatin and fenofibrate in subjects with the metabolic syndrome. , 2003, Diabetes.

[19]  R. Collins,et al.  Heart Protection Study , 2003, The Lancet.

[20]  James W. Anderson,et al.  Diabetes, plasma insulin, and cardiovascular disease: subgroup analysis from the Department of Veterans Affairs high-density lipoprotein intervention trial (VA-HIT). , 2002, Archives of internal medicine.

[21]  S. Grundy,et al.  ACC/AHA/NHLBI Clinical Advisory on the Use and Safety of Statins. , 2002, Circulation.

[22]  M. Taskinen Diabetic dyslipidemia. , 2002, Atherosclerosis. Supplements.

[23]  J. Wittes,et al.  Relation of gemfibrozil treatment and lipid levels with major coronary events: VA-HIT: a randomized controlled trial. , 2001, JAMA.

[24]  Bezafibrate Infarction Prevention study Secondary prevention by raising HDL cholesterol and reducing triglycerides in patients with coronary artery disease. , 2000, Circulation.

[25]  Teven,et al.  MORTALITY FROM CORONARY HEART DISEASE IN SUBJECTS WITH TYPE 2 DIABETES AND IN NONDIABETIC SUBJECTS WITH AND WITHOUT PRIOR MYOCARDIAL INFARCTION , 2000 .

[26]  T. Wilt,et al.  Gemfibrozil for the secondary prevention of coronary heart disease in men with low levels of high-density lipoprotein cholesterol. Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial Study Group. , 1999, The New England journal of medicine.

[27]  R. Holman,et al.  Risk factors for coronary artery disease in non-insulin dependent diabetes mellitus: United Kingdom prospective diabetes study (UKPDS: 23) , 1998, BMJ.

[28]  L. Tenkanen,et al.  Some coronary risk factors related to the insulin resistance syndrome and treatment with gemfibrozil. Experience from the Helsinki Heart Study. , 1995, Circulation.

[29]  J. Neaton,et al.  Diabetes, Other Risk Factors, and 12-Yr Cardiovascular Mortality for Men Screened in the Multiple Risk Factor Intervention Trial , 1993, Diabetes Care.

[30]  J. Huttunen,et al.  Lipid alterations and decline in the incidence of coronary heart disease in the Helsinki Heart Study. , 1988, JAMA.

[31]  H. Ginsberg,et al.  Changes in lipoprotein kinetics during therapy with fenofibrate and other fibric acid derivatives. , 1987, The American journal of medicine.

[32]  S. Grundy,et al.  Fibric acids: effects on lipids and lipoprotein metabolism. , 1987, The American journal of medicine.

[33]  J. Huttunen,et al.  Helsinki Heart Study: primary-prevention trial with gemfibrozil in middle-aged men with dyslipidemia. Safety of treatment, changes in risk factors, and incidence of coronary heart disease. , 1987, The New England journal of medicine.

[34]  A. Kissebah,et al.  Low Density Lipoprotein Metabolism in Familial Combined Hyperlipidemia: Mechanism of the Multiple Lipoprotein Phenotypic Expression , 1984, Arteriosclerosis.

[35]  M. Karvonen,et al.  A co-operative trial in the primary prevention of ischaemic heart disease using clofibrate. , 1979, British heart journal.

[36]  D. Grafnetter,et al.  A co-operative trial in the primary prevention of ischaemic heart disease using clofibrate. Report from the Committee of Principal Investigators. , 1978, British heart journal.

[37]  J. Stamler Clofibrate and niacin in coronary heart disease. , 1975, JAMA.