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Fournier Pharma Announces Results of the Largest Clinical Trial in Patients With Type 2 Diabetes Demonstrating Positive Effects of Fenofibrate Therapy on Cardiovascular Events
Dallas, Texas, November 14 (ots/PRNewswire) -
- FIELD Confirms Fenofibrate Produces Macrovascular and Microvascular Benefits in Diabetic Patients Without Previous Cardiovascular Disease Although Primary Endpoint is not met
Results of the largest intervention study ever conducted for the prevention of cardiovascular disease in people with diabetes showed that patients treated with fenofibrate had a reduced rate of total cardiovascular events - a pre-specified secondary endpoint defined as a composite of cardiovascular death, myocardial infarction (MI), stroke and coronary and carotid revascularizations - compared to patients treated with placebo. In addition to the macrovascular benefit, the findings also suggested a beneficial effect of fenofibrate on microvascular complications associated with diabetes, specifically renal and eye disease.
Results of the landmark Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study were presented today at the annual congress of the American Heart Association and published online in The Lancet.
"People with type 2 diabetes face a three- to four-fold higher risk for cardiovascular disease than those without diabetes and more than half of people with diabetes will die from cardiovascular disease," said Professor Anthony Keech, MD, University of Sydney, Australia, and FIELD principal investigator. "The FIELD study findings indicate that fenofibrate reduces the risk of cardiovascular disease, mainly through the prevention of non-fatal myocardial infarctions and coronary revascularizations."
FIELD study design
FIELD was a double-blind, randomised, placebo-controlled trial which recruited 9795 patients in Australia, New Zealand and Finland. The primary outcome of the trial was coronary events (coronary heart disease [CHD] death or non-fatal MI). The outcome for pre-specified subgroup analyses was total cardiovascular events, defined as the combined incidence of cardiovascular death, MI, stroke and coronary and carotid revascularizations. Tertiary criteria included measures of renal disease (progression of albuminuria) and diabetic eye disease (laser treatment for retinopathy).
Patients were on treatment for a median of five years and evaluated for the effect of micronised fenofibrate once daily versus placebo on coronary heart and cardiovascular disease in patients with type 2 diabetes. Participants were evaluated every six months for outcome events and safety assessments.
The FIELD study was unique in that the patient population includes the largest subgroup of primary prevention patients ever included in a type 2 diabetes trial; 7664 patients (78% of the study population) showed no signs of prior cardiovascular disease at study entry. The median duration of diabetes was 5 years and the patients' blood glucose levels were well controlled (median HbA1c = 6.9%). Three-fifths (60%) of patients were on diet recommendations or monotherapy alone for their diabetes. Moreover, few patients at baseline suffered from retinopathy (8%) or nephropathy (3%). About one-third (38%) of patients had both triglyceride concentrations of > 1.7 mmol/l and HDL-cholesterol levels of < 1.03 mmol/l in men and < 1.29 mmol/l in women. The majority (60%) of patients were under 65 years of age at screening.
FIELD study results
For the study's primary endpoint of coronary events (coronary heart disease death or non-fatal MI), patients treated with fenofibrate experienced an 11-percent reduction in events versus placebo (5% vs 6%, p=0.16), a statistically non-significant difference. For the study's pre-specified secondary endpoint of total cardiovascular events, patients on fenofibrate experienced a statistically significant 11-percent reduction in total events versus placebo (13% vs 14%, p=0.035). There was an overall 21-percent reduction of coronary revascularization (6% vs 7%, p=0.003), also a pre-specified secondary endpoint.
Treatment effects were significantly larger in the patients with no previous cardiovascular disease than in those with previous cardiovascular disease (comprising 78% of all trial participants). In this subgroup of patients, investigators reported:
- A significant 19-percent reduction in total cardiovascular disease events (p<0.004, secondary endpoint), corresponding to an absolute risk reduction rate of 2 percent, or the equivalent of needing to treat 50 patients for 5 years to prevent one or more CVD events in one patient;
- A significant 25-percent reduction in coronary events (p=0.014, primary endpoint) in a post-hoc subgroup analysis.
There were more coronary deaths and fewer other vascular deaths in the fenofibrate group, neither being statistically significant (both p>0.2). There was also a non-significant increase in total mortality that was not linked to any particular cause and was consistent with statistical chance.
In the total population of FIELD, study investigators reported a favourable effect of treatment with fenofibrate on the progression of albuminuria (an early indicator of renal disease), as previously reported in the DAIS trial. Another important finding was the significant, favourable effect of fenofibrate on the need for one or more laser treatments for retinopathy.
- Progression to albuminuria was significantly reduced by fenofibrate, with 466 fenofibrate-allocated patients (10%) progressing from normo- to microalbuminuria or from micro- to macroalbuminuria, compared to 539 patients (11%) allocated placebo and more frequent regression of albuminuria also occurred with fenofibrate (p=0.002 for all shifts); in addition, the number of patients requiring dialysis during the study was 21 in those taking placebo and 16 in patients taking fenofibrate.
- Significantly fewer patients assigned fenofibrate needed one or more retinal laser treatments (n=178, 3.6%) than controls taking placebo (n=253, 5.2%), representing a 30-percent reduction (p=0.0003).
Taken together, these findings suggest a beneficial effect of fenofibrate on the microvasculature, which cannot be explained by changes in HbA1c or concomitant medications, or by the minor reduction in blood pressure in the fenofibrate group. This is the first time that a lipid-lowering agent has been shown to reduce the risk of macrovascular and microvascular events in a large-scale clinical study in patients with type 2 diabetes.
Physicians participating in the study were also allowed to add at their discretion other medications commonly used in diabetic patients, including lipid-lowering agents (such as statins), anti-hypertensives, and anti-thrombotics. By the end of the study, twice as many patients in the placebo arm were receiving statins versus the fenofibrate group (32% vs 16%, p<0.0001).
The significantly more common use of statin therapy among patients allocated placebo in FIELD may have masked a larger treatment benefit from fibrate therapy. After adjustment for new lipid-lowering agents, in a time-dependent Cox regression analysis, fenofibrate reduced the risk of coronary heart disease events by 19 percent (p=0.01) and of total cardiovascular disease events by 15 percent (p=0.004).
"People with type 2 diabetes have been well represented in other landmark trials of lipid-lowering treatment for the secondary prevention of cardiovascular disease, but what is interesting about the FIELD trial is that it shows that fenofibrate treatment can prevent macro- and microvascular complications in people in early stages of type 2 diabetes with or without dyslipidaemia," concluded Professor Keech.
FIELD study: Tolerance
Fenofibrate was generally well tolerated irrespective of concomitant therapy. Similar numbers of patients in the placebo and fenofibrate groups discontinued treatment. Twenty-four (0.5%) patients on placebo and 38 (0.8%) on fenofibrate had possible serious adverse drug reactions. One patient on placebo, and three allocated fenofibrate had rhabdomyolysis, which fully resolved in each case. More patients allocated to fenofibrate than those on placebo experienced pancreatitis (0.8% vs 0.5%), but the numbers were small. There were also small reported increases of pulmonary embolism (1.0% vs 0.7%) and deep vein thrombosis (1.4% vs 1.0%) associated with fenofibrate.
Commenting on the implications of FIELD, study investigators, reporting in The Lancet, have suggested that "FIELD provides information to help guide clinicians on the future use of fenofibrate in patients with type 2 diabetes." Further, "the results are likely to be of particular importance among patients without previous cardiovascular disease and in settings where both the prevention of non-fatal macrovascular events and microvascular complications are judged important."
Notes to Editors:
FIELD study endorsements, locations, co-ordination and sponsorship
The FIELD study is endorsed by the National Heart Foundation of Australia, Diabetes Australia, the New Zealand Society for the Study of Diabetes and the Finnish Diabetes Association. The FIELD study was conducted at 63 sites in Australia, Finland and New Zealand and was coordinated independently of the sponsors by the National Health and Medical Research Council (NHMRC) Clinical Trials Centre, University of Sydney, Sydney, Australia. Laboratoires Fournier SA, of Dijon, France, sponsored FIELD and supplied fenofibrate and matching placebo medication.
Fenofibrate is approved for use in nearly 80 countries worldwide. Approximately 26 million prescriptions have been written and the cumulative number of patients who have received Lipanthyl is about 32 million. Fenofibrate is registered as Lipanthyl(R), Tricor(R), Lipidil(R), Fulcro(R), Secalip(R) and Catalip(R).
About Fournier Pharma
Fournier Pharma is dedicated to improving health and quality of life through innovative healthcare products and services for the prevention and treatment of human diseases.
With a turnover of 593 million Euros in 2004, Fournier Pharma employs 3,400 people across 30 sites in all key markets of the world, with France and the USA being its leading markets.
Soundly established on a bedrock of 30 years experience in research into lipid disorders and cardiovascular diseases, Fournier Pharma focuses its activities onto treating metabolism pathologies and preventing cardiovascular risk.
With an investment in research and development accounting for 13% of its turnover, Fournier Pharma focuses on the discovery of new drug targets and innovative drugs in the field of metabolic diseases.
Fournier Pharma has a promising portfolio in the cardio-metabolic field, including Dualtis(R), a combination of fenofibrate and metformin, other associations of products, as well as research projects concerning nuclear receptors.
For more details, please visit www.fournierpharma.com.
Fournier Pharma was acquired by the Belgian company Solvay in 2005.
SOLVAY is an international chemicals and pharmaceuticals group with headquarters in Brussels. It is present in more than 50 countries and employs some 33,000 people in its Chemicals, Plastics and Pharmaceuticals activities. Including Fournier Pharma, its sales amounted to EUR 8.5 million in 2004. Solvay is listed on the Euronext 100 index of top European companies.
Details are available at www.solvay.com.
- Type 2 diabetes mellitus is a disease with a dramatically increasing prevalence throughout the world. The global disease burden is mainly driven by an increased risk of cardiovascular disease as well as microvascular diseases such as end-stage renal disease and blindness.
- There are currently more than 194 million people with diabetes worldwide. If nothing is done to slow the epidemic, the number will exceed 333 million by 2025.
- Diabetes is the fourth main cause of death in most developed countries.
- Diabetes is the leading cause of blindness and visual impairment in adults in developed countries.
- Cardiovascular disease is the number-one cause of death in industrialized countries. It is also set to overtake infectious diseases as the most common cause of death in many parts of the less developed world.
- People with diabetes are two to four times more likely to develop cardiovascular disease than people without diabetes.
- The populations of most countries are ageing. Diabetes is particularly common in ageing populations and is increasing in proportion to the number of people living longer.
- The devastating complications of diabetes, such as blindness, kidney failure and heart disease, are imposing a huge burden on healthcare services. It is estimated that diabetes accounts for between 5% and 10% of a nation's health budget.
More information and a full media kit is available in the Exhibitors' Newsroom
 Keech, A, et al. "The Effect of Fenofibrate on Major Coronary Heart Disease (CHD) Events in People With Type 2 Diabetes: the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) Study." 4. Presented at the Scientific Sessions of the American Heart Association congress, 14 November 2005.
 Ansquer JC, Foucher C, Rattier S, Taskinen MR, Steiner G for the DAIS investigators. Fenofibrate reduces progression to microalbuminuria over 3 years in the placebo-controlled study in type 2 diabetes: results from Diabetes Atherosclerosis Intervention Study (DAIS). Am J Kidney Dis 2005; 45: 485-93.
ots Originaltext: Fournier Pharma
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