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Fenofibrate (TriCor, Abbott; Antara, Reliant) failed to achieve the primary outcome of risk reduction of coronary events, defined as coronary heart disease, death, or nonfatal heart attack, in the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study.
However, the secondary end point of reduction of total cardiovascular events was achieved, says lead investigator Anthony Keech, MD, professor of medicine at the University of Sydney in Australia. This was due primarily to a statistically significant 24% decrease in nonfatal heart attacks and a 21% decrease in the need for revascularization, he reports.
Keech presented the findings at the American Heart Association's Scientific Sessions, held November 13–16 in Dallas. With almost 10,000 subjects, FIELD was the largest prospective study examining the effects of a cholesterol-lowering medication on cardiovascular outcomes in a diabetic population. Patients with type 2 diabetes have a three- to fourfold risk for developing cardiovascular disease compared with people without diabetes.
When lifestyle changes are unsuccessful, fenofibrate is sometimes used to treat adults with high cholesterol and/or mixed dyslipidemia with or without elevated triglycerides. It reduces elevated LDL cholesterol, total cholesterol, triglycerides, and apolipoprotein B, and increases HDL cholesterol.
The FIELD patients had total cholesterol levels of 116–251 mg/dl
(3–6.5 mmol/l), total cholesterol/HDL cholesterol ratios 
4, and
plasma triglycerides of 89–133 mg/dl (1–1.5 mmol/l). None of the
patients was on statin therapy; 2,131 had a history of cardiovascular disease,
and 7,664 did not.
The study involved a 16-week run-in phase of 4 weeks of dietary modification followed by 6 weeks of placebo and 6 weeks of fenofibrate therapy. Patients then were randomized to fenofibrate (200 mg daily) or placebo.
The drug discontinuation rate was 10% in the placebo group and 11% in the fenofibrate group. Treating physicians were free to prescribe additional therapies as they deemed appropriate, and initiation of other lipid-lowering treatments was higher in the placebo group (17%) than in the study group (8%). These treatments were primarily statins.
Once the study was unblinded, investigators saw that placebo patients had received "more aggressive background therapy."
"This finding might have masked a moderately larger treatment benefit" with fenofibrate therapy, Keech says.
Coronary events occurred in 5% of placebo patients and 5.2% of fenofibrate patients, for a relative reduction of 11%.
"This finding corresponds to a significant 24% reduction in nonfatal myocardial infarction and a nonsignificant increase in coronary heart disease mortality," FIELD researchers write in an article in The Lancet1 published to coincide with the study's presentation in Dallas.
Total mortality over the course of the 5-year study was 7.3% in the fenofibrate group and 6.6% in the placebo group. Total cardiovascular events were reduced from 13.9% to 12.5%. In particular, the need for coronary revascularization was significantly reduced by 21%. There were nonsignificant increases in pulmonary embolism and pancreatitis.
"In summary, there were mixed effects with fenofibrate therapy," Keech concludes. There was no improvement in survival with fenofibrate, but there was a significant reduction in nonfatal myocardial infarction and a strongly significant reduction in microvascular events.
Keech draws attention to the drug's effect on microvascular-related risks—significantly less progression of albuminuria, a 30% reduction in laser treatment for retinopathy, and a 30% reduction in amputations in patients on active treatment.
"We are not arguing to replace statins with fenofibrate, but there is an advantage of adding fenofibrate to statin therapy," Keech says. "The results of FIELD will add to the growing body of knowledge of how best to manage cardiovascular risks within this patient population."
An Abbott statement warns that the combined use of fenofibrate and statin drugs "may produce potentially serious side effects that could lead to acute renal failure." A health care professional should determine if the benefits of the combined use of these drugs are likely to outweigh the increased risks of their combination, Abbott says.
The FIELD results published in The Lancet were accompanied by an editorial by Helen Colhoun, MD, professor of genetic epidemiology at the Conway Institute of the University of Dublin in Ireland.2
"Results from this well-executed trial do not warrant a
recommendation for increased fenofibrate use in patients with diabetes, nor do
they provide convincing evidence of the benefit of fenofibrate therapy in
patients already at target serum LDL cholesterol," Colhoun writes.
References
2. Colhoun H: After FIELD: Should fibrates be used to prevent cardiovascular disease in diabetes? Lancet 366: 1829–1831, 2005.[Medline]
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