ACC: Fibrate+statin therapy does not lower CV events in adult diabetics
ATLANTA—Treating multiple blood lipids with combination drug therapy of a fibrate and a statin did not reduce the combined risk of cardiovascular disease events more than treatment with statins alone, according to the ACCORD trial presented today at the late-breaking clinical tirals session at ACC.10.

The entire ACCORD (Action to Control Cardiovascular Risk in Diabetes) trial embraced more than 10,251 adult participants, between the ages of 40 and 79, who had type 2 diabetes for an average of 10 years and were at especially high risk of cardiovascular events, such as heart attacks, stroke or cardiac death. The ACCORD lipid trial involved 5,518 participants.

The 77-site clinical trial tested three potential strategies to lower the risk of major cardiovascular events: intensive control of blood sugar, intensive control of blood pressure and treatment of multiple blood lipids. The lipids targeted for intensive treatment were HDL cholesterol and triglycerides, in addition to standard therapy of lowering LDL cholesterol.

The results of the ACCORD lipid trial appear online in the New England Journal of Medicine today. Results of the ACCORD blood sugar clinical trial were reported in 2008.

The ACCORD lipid trial studied whether adding a fibrate to a statin to improve multiple blood lipids is more effective at lowering the risk of cardiovascular events than treatment with a statin alone. Both statins and fibrates are commonly used medications to treat abnormal levels of blood lipids. Statins lower LDL and are proven to lower cardiovascular disease risk in people with diabetes. Fibrates primarily lower fats in the blood known as triglycerides and raise HDL. Fibrates are sometimes used in combination with statins. High triglycerides and low HDL levels are common in diabetes patients.

ACCORD compared the cardiovascular effects of a statin (simvastatin) and placebo, or inactive pill, to combination therapy of a statin (simvastatin) and a fibrate (fenofibrate, Tricor; Abbott) in high-risk adults with type 2 diabetes.

Overall, the combination therapy was safe, but it did not lower the risk of heart attack, stroke or death from cardiovascular disease more than statins alone, reported lead author Henry N. Ginsberg, MD, director of the Irving Institute for Clinical and Translational Research at Columbia University College of Physicians and Surgeons in New York City.

The researchers also found that participants who started the study with the lowest levels of HDL cholesterol plus the highest levels of triglycerides had lower rates of cardiovascular events if they received the combination therapy compared to similar participants who received only statin therapy. Although a similar effect has been seen in other studies, more research is needed of the effects on this subgroup, which comprised 17 percent of the ACCORD participants.

"Overall, the results of the ACCORD lipid trial do not support the use of combination therapy with a fibrate and a statin to reduce cardiovascular disease in most high-risk adults with type 2 diabetes," said Ginsberg. "Although our analysis suggests that certain patients may benefit from combination therapy, this study provides important information that should spare many people with diabetes unneeded therapy with fibrates."

In his response to the ACCORD lipid trial, Paul D. Thompson, MD, from the Hartford Hospital in Hartford, Conn., noted that the trial incorporated many different patient types, with various triglyceride levels. “The average triglyceride level was only 162, so it’s not very surprising that there were not definitive improvements in the overall group of diabetics," he said.

Thompson also questioned whether 4.7 years was long enough to draw the conclusions that this study has drawn. “When you are looking at a relatively weak risk factor in triglycerides, is this trial long enough to properly assess fibrate therapy added to statin therapy?” he asked. “It may take longer to affect cardiovascular disease.”

Also, Thompson said that he doesn’t think this trial will have much effect on clinical practice, since the drug isn’t currently being routinely used with diabetics.

In a subset analysis of the ACCORD lipid trial, the researchers found that men may have benefitted from the combination lipid therapy whereas women on combination therapy appeared to have more cardiovascular problems than those on statins alone.

"The lack of benefit from fibrates should not obscure the proven value of statins in preventing cardiovascular disease, which is well established from earlier studies," Ginsberg added. "Patients should discuss with their health care provider the implications of this research for their lipid therapy management."

Thompson noted that this therapy showed some benefits for diabetic patients in the high triglyceride lower HDL group, and future studies should address this issue.

The researchers cautioned that the results from ACCORD might not apply to patients who are at lower risk of cardiovascular disease than the ACCORD participants or to patients with more recently diagnosed type 2 diabetes.

The National Institutes of Health supported the comprehensive ACCORD trial.