Fenofibrate Intervention and Event Lowering in Diabetes FIELDFIELD Presented at The American Heart Association Scientific Sessions, November 2005 Presented by Dr. Anthony Keech

www. Clinical trial results.org FIELD: Background Statins, whose main action is to lower LDL, have been shown to have significant beneficial effects in diabeticsStatins, whose main action is to lower LDL, have been shown to have significant beneficial effects in diabetics Fibrates affect different components of the lipid profile by preferentially increasing HDL, lowering triglycerides, and increasing the size of LDL particlesFibrates affect different components of the lipid profile by preferentially increasing HDL, lowering triglycerides, and increasing the size of LDL particles Fibrates could be beneficial for diabetics in whom low HDL, high triglycerides, and small LDL particles are more common than in the general populationFibrates could be beneficial for diabetics in whom low HDL, high triglycerides, and small LDL particles are more common than in the general population The goal of the study is to evaluate treatment with fenofibrate compared with placebo in patients with diabetes who are at risk for coronary heart diseaseThe goal of the study is to evaluate treatment with fenofibrate compared with placebo in patients with diabetes who are at risk for coronary heart disease ● AHA 2005

www. Clinical trial results.org Fenofibrate (200 mg daily) n=4895 Fenofibrate (200 mg daily) n=4895 Endpoints:  Primary – Composite of CHD death or non-fatal MI at 5 year follow-up  Secondary – Composite of total CV events, CV mortality, total mortality, stroke, coronary revascularization and all revascularization at 5 year follow-up Endpoints:  Primary – Composite of CHD death or non-fatal MI at 5 year follow-up  Secondary – Composite of total CV events, CV mortality, total mortality, stroke, coronary revascularization and all revascularization at 5 year follow-up FIELD: Design ESC 2005 Placebo N=4900 Placebo N= patients, Age years, type 2 diabetes diagnosed after age 35 years, no clear indication for cholesterol-lowering therapy at baseline (total cholesterol mg/dL, plus either total cholesterol to HDL ratio ≥4.0 or triglyceride >88.6 mg/dL

www. Clinical trial results.org FIELD: Primary Endpoint The primary composite endpoint of CHD death or non-fatal MI was not significantly lower in the fenofibrate group compared to the placebo group. The primary composite endpoint of CHD death or non-fatal MI was not significantly lower in the fenofibrate group compared to the placebo group. Composite CHD death or nonfatal MI at 5 Years (% of treatment arm) AHA 2005 p=0.16

www. Clinical trial results.org FIELD: Primary Endpoint CHD death was not significantly different between treatment groupsCHD death was not significantly different between treatment groups Nonfatal MI was significantly lower in the fenofibrate group compared with the placebo group.Nonfatal MI was significantly lower in the fenofibrate group compared with the placebo group. CHD death or nonfatal MI at 5 year follow-up (% of treatment arm) P=0.22 P=0.01 AHA 2005

www. Clinical trial results.org FIELD: Secondary Endpoint The secondary composite endpoint of total CV events was significantly lower in the fenofibrate group compared to the placebo group (% of treatment arm) The secondary composite endpoint of total CV events was significantly lower in the fenofibrate group compared to the placebo group (% of treatment arm) Secondary Composite Endpoint of Total CV events at 5 year Follow-up p=0.035 AHA 2005

www. Clinical trial results.org FIELD: Secondary Endpoint CV Mortality, Total Mortality, and Stroke were not significantly different between the fenofibrate and placebo groups Individual Components of Secondary Endpoint p=0.41 p=0.18 p=0.36 AHA 2005

www. Clinical trial results.org FIELD: Secondary Endpoint Percentage of coronary revascularization and all revascularization were significantly lower in the fenofibrate group compared to placebo Individual Components of Secondary Endpoint P=0.003 P=0.001 AHA 2005

www. Clinical trial results.org FIELD: Limitations The results of this study may have been confounded by uneven use of statins between the two groups as 17% of the placebo group was prescribed a statin during the trial compared with 7% in the fenofibrate groupThe results of this study may have been confounded by uneven use of statins between the two groups as 17% of the placebo group was prescribed a statin during the trial compared with 7% in the fenofibrate group Although adjusting for statin use yields a statistically significant reduction in the primary endpoint (19%, p=0.01) this may slightly overestimate the effect for the fenofibrate group since the use of statins was not randomizedAlthough adjusting for statin use yields a statistically significant reduction in the primary endpoint (19%, p=0.01) this may slightly overestimate the effect for the fenofibrate group since the use of statins was not randomized In terms of adverse effects, the fenofibrate group showed small increases in pancreatitis (0.5% vs 0.8%, p=0.031) and pulmonary embolism (0.7% vs 1.1%, p=0.022)In terms of adverse effects, the fenofibrate group showed small increases in pancreatitis (0.5% vs 0.8%, p=0.031) and pulmonary embolism (0.7% vs 1.1%, p=0.022) Although fenofibrate reduced triglycerides and LDL, there was virtually no increase shown in HDLAlthough fenofibrate reduced triglycerides and LDL, there was virtually no increase shown in HDL AHA 2005

www. Clinical trial results.org FIELD: Summary Among patients with diabetes at risk of coronary heart disease, there was no statistically significant difference in the primary composite endpoint of CHD death or nonfatal MI. There was, however, a significant reduction in nonfatal MI in the fenofibrate group compared with placebo. The secondary composite endpoint of total cardiovascular events was significantly lower in the fenofibrate group primarily due to reductions in nonfatal MI and revascularizations. The secondary composite endpoint of total cardiovascular events was significantly lower in the fenofibrate group primarily due to reductions in nonfatal MI and revascularizations. The results may have been confounded by a difference in statin use between the two groups as 17% of the placebo group were prescribed statins during the trial compared to 7% in the fenofibrate group. This may have attenuated treatment effect differences.The results may have been confounded by a difference in statin use between the two groups as 17% of the placebo group were prescribed statins during the trial compared to 7% in the fenofibrate group. This may have attenuated treatment effect differences. The ACCORD trial, which will randomize diabetics to either fenofibrate or placebo with all patients taking simvastatin, will provide a more definitive answer regarding the benefit of fenofibrates in diabetics.The ACCORD trial, which will randomize diabetics to either fenofibrate or placebo with all patients taking simvastatin, will provide a more definitive answer regarding the benefit of fenofibrates in diabetics. Among patients with diabetes at risk of coronary heart disease, there was no statistically significant difference in the primary composite endpoint of CHD death or nonfatal MI. There was, however, a significant reduction in nonfatal MI in the fenofibrate group compared with placebo. The secondary composite endpoint of total cardiovascular events was significantly lower in the fenofibrate group primarily due to reductions in nonfatal MI and revascularizations. The secondary composite endpoint of total cardiovascular events was significantly lower in the fenofibrate group primarily due to reductions in nonfatal MI and revascularizations. The results may have been confounded by a difference in statin use between the two groups as 17% of the placebo group were prescribed statins during the trial compared to 7% in the fenofibrate group. This may have attenuated treatment effect differences.The results may have been confounded by a difference in statin use between the two groups as 17% of the placebo group were prescribed statins during the trial compared to 7% in the fenofibrate group. This may have attenuated treatment effect differences. The ACCORD trial, which will randomize diabetics to either fenofibrate or placebo with all patients taking simvastatin, will provide a more definitive answer regarding the benefit of fenofibrates in diabetics.The ACCORD trial, which will randomize diabetics to either fenofibrate or placebo with all patients taking simvastatin, will provide a more definitive answer regarding the benefit of fenofibrates in diabetics. AHA 2005