ACCORD Lipid Study Brings new Hope to People With Type 2 Diabetes and Atherogenic Dyslipidemia Says International Academic Foundation

ATLANTA, Georgia, March 14, 2010 /PRNewswire/ -- Cardiovascular risk can be reduced by an additional 31 percent in type 2 diabetes patients with atherogenic dyslipidemia, the common combination of elevated triglycerides (TG, 204 mg/dL or 2.3 mmol/L or higher) and low levels of high-density lipoprotein cholesterol (HDL-C, 34 mg/dL or 0.88 mmol/L or lower). This is achieved by adding fenofibrate to simvastatin. Only 20 of these patients need to be treated for 5 years to prevent one cardiovascular event.

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In the Action to Control Cardiovascular Risk in Diabetes (ACCORD) Lipid trial, published on-line in the New England Journal of Medicine,(1) the group with atherogenic dyslipidemia had 70 percent more cardiovascular events (cardiovascular death, heart attacks and strokes) than patients without. In fact, the risk associated with atherogenic dyslipidemia was comparable to that in people with previous cardiovascular disease (17.3 percent versus 18.1 percent).

Professor Jean-Charles Fruchart, President of the Residual Risk Reduction Initiative (R3i), an independent Swiss academic foundation, said: 'For the last two years, the R3i has focused on the hypothesis that residual cardiovascular risk in statin-treated patients is associated with atherogenic dyslipidemia.(2,3) ACCORD Lipid confirms both the hypothesis and the value of adding fenofibrate to a statin to reduce this high residual cardiovascular risk. This is consistent with current guidelines from the American Diabetes Association(4) and the National Cholesterol Education Program Adult Treatment Panel III.(5)'

The benefit of fenofibrate was only seen in the pre-specified group of diabetic patients with atherogenic dyslipidemia and not in the total study population. 'While patients with atherogenic dyslipidemia only represented 17 percent of the ACCORD Lipid population, in clinical practice the size of the problem is significantly greater. We are now quantifying this in the R3i-funded REsiduAl risk Lipids and Standard Therapies (REALIST) study which is being conducted at Harvard Medical School and over 20 well-known academic centers worldwide,' said Professor Frank Sacks of Harvard Medical School, Boston, USA and Vice-President of the R3i.

In ACCORD Lipid, fenofibrate also reduced micro- and macro-albuminuria, markers of diabetic renal disease. This is consistent with results from earlier clinical trials.(6,7) 'Diabetic nephropathy is a major management issue. Therefore it is important knowledge that fenofibrate provides benefit to these patients,' said Professor Michel Hermans of Cliniques Universitaires Saint-Luc, Brussels, Belgium and General Secretary of the R3i.

The study also confirmed that adding fenofibrate to simvastatin did not result in any excess risk of myopathy (muscle problems), venous thrombosis or pancreatitis. In fact, there were fewer all-cause and cardiovascular deaths in fenofibrate-treated patients than in patients treated with simvastatin alone.

R3i leads new research into atherogenic dyslipidemia in type 2 diabetes

Atherogenic dyslipidemia is common and the prevalence is markedly increasing as a result of the global epidemic of type 2 diabetes, obesity and metabolic syndrome.(8) So, in the U.S. about half of the high- risk patients beginning statin therapy may require additional treatment to lower their triglycerides and/or to raise their HDL-C.(9)

The R3i is responding to this critically important clinical problem. 'Given the magnitude of the global epidemic of type 2 diabetes - especially in developing regions - targeting atherogenic dyslipidemia is crucial. As the only independent global research foundation focusing on this issue, the R3i is urgently developing recommendations for evidence-based strategies to reduce residual vascular risk. Currently, we are conducting the first world-wide epidemiological study, REALIST, to establish the prevalence of atherogenic dyslipidemia and consequent residual risk of cardiovascular events. Now, as a result of ACCORD Lipid, we will also initiate a meta-analysis of the atherogenic dyslipidemic subgroups of patients (high TG and/or low HDL-C) in previous fibrate studies,' said Professor Fruchart.

Notes to Editors

About ACCORD

The ACCORD study was sponsored by the National Heart, Lung, and Blood Institute (NHLBI), part of the National Institutes of Health (NIH) in the U.S, and was conducted across the U.S. and Canada. The key question addressed in the ACCORD Lipid treatment arm was whether the combination of fenofibrate plus simvastatin, i.e. targeting elevated TG and low HDL-C in addition to LDL-C, was more effective in reducing cardiovascular events than statin therapy alone in a cohort of 5,518 high-risk patients with controlled type 2 diabetes mellitus at target for LDL-C. Fenofibrate was chosen because subgroup analyses from previous trials had shown added benefits in patients with type 2 diabetes, or in those with abdominal obesity characteristic of the metabolic syndrome.(10-14) No other clinical trial had previously tested this strategy.

However, the population treated was broader than that recommended by current guidelines for fenofibrate. More than 80 percent of patients did not have sufficiently elevated TG and low HDL-C warranting treatment according to current clinical practice.

ACCORD Lipid established that extending fenofibrate treatment to this broader population did not significantly benefit any of the primary or secondary cardiovascular outcomes in the total study population. However, the study did show a substantial reduction in cardiovascular events with fenofibrate-simvastatin treatment in patients with atherogenic dyslipidemia, with event rates decreasing from 17.3 percent in the simvastatin monotherapy group to 12.4 percent with combination treatment over 4.7 years. This result supports current guidelines and common clinical practice.

More information on the R3i is available from:

The R3i website: http://www.r3i.org

References

1. The ACCORD Study Group. Effects of combination lipid therapy in type 2 diabetes mellitus. N Eng JMed 2010. DOI:10.1056/NEJMoa1001282.

2. Fruchart JC, Sacks FM, Hermans MP et al. The Residual Risk Reduction Initiative: a call to action to reduce residual vascular risk in dyslipidaemic patients. Diab Vasc Dis Res 2008;5:319-35.

3. Fruchart JC, Sacks FM, Hermans MP et al. The Residual Risk Reduction Initiative: a call to action to reduce residual vascular risk in dyslipidemic patients. Am J Cardiol 2008;102(10 Suppl):1K-34K.

4. American Diabetes Association. Standards of medical care in diabetes-2008. Diabetes Care 2008; 31(suppl 1): S12-S54. [Updated 2009: Executive Summary: Standards of Medical Care in Diabetes-2009. Diabetes Care 2009;32 (suppl 1):S6-S12.]

5. National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). 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;106:3143-421.

6. Keech A, Simes RJ, Barter P et al. The FIELD study investigators. Effect 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.

7. Ansquer JC, 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 (DIAS). Am J Kidney Dis 2005;45: 485-93.

8. International Diabetes Federation. E-Atlas available at http://www.diabetesatlas.org/. [Accessed 12 March 2010].

9. Nichols GA, Ambegaonkar BM, Sazonov V et al. Frequency of obtaining National Cholesterol Education Program Adult Treatment Panel III goals for all major serum lipoproteins after initiation of lipid altering therapy. Am J Cardiol 2009;104:1689-94.

10. Scott R, O'Brien R, Fulcher G et al. The effects of fenofibrate treatment on cardiovascular disease risk in 9795 people with type 2 diabetes and various components of the metabolic syndrome: the FIELD study. Diabetes Care 2009;32:493-8.

11. 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.

12. 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;162:2597-2604.

13. Tenkanen L, Mantarri M, Manninen V. Some coronary risk factors related to the insulin resistance syndrome and treatment with gemfibrozil: experience from the Helsinki Heart Study. Circulation 1995; 92: 1779-85.

14. Tenenbaum A, Motro M, Fisman EZ, Tanne D, Boyko V, Behar S. Bezafibrate for the secondary prevention of myocardial infarction in patients with metabolic syndrome. Arch Intern Med 2005; 165: 1154-60.

SOURCE Residual Risk Reduction initiative (R3i)