Questionable Benefit for Fibrates

The increased use of fibrates contrasts with results from clinical trials showing no benefit of fibrate therapy in diabetic patients already taking statins….

The use of fibrates in the US has increased steadily over the past 10 years and remained consistent in Canada, with the market share dominated by brand-name fenofibrate over generic formulations,

Lead investigator Dr. Cynthia Jackevicius (Western University of Health Sciences, Pomona, CA) said that, “We didn’t have patient-specific lipid profiles, so we can’t say whether there is too much use or whether it is appropriate for a specific patient.” “All we know is that use is increasing over time, even though there is no new evidence to suggest any benefit. There does appear to be some disconnect between the evidence and practice. Of course, you never want patients to stop any medication without talking to their doctors, but the clinician might not recognize the updated evidence or what the guidelines actually say. This is an opportunity to see if their patients meet the criteria for using fibrates.”

The researchers noted that fenofibrate, rather than generic formulations of fibrates, dominated the marketplace. In the US, fenofibrate prescriptions increased from 150 to 440 per 100,000 individuals from 2002 to 2009, an increase of 159%. In fact, fenofibrate prescriptions constituted 48% of all fibrate prescriptions in 2002, but this share increased to 65% in 2009.

“Fibrates are popularly used, both in the US and in Canada,” said Jackevicius, “but evidence to support their use isn’t strong. The drugs are mainly indicated for high triglyceride levels. Nonetheless, prescriptions for fibrates have gone up dramatically, and one of the drugs in particular, fenofibrate, really dominates the market in both countries and is what particularly drove the increased use in the US.”

Fibrates are a guideline-recommended treatment for the reduction of elevated triglyceride levels and diabetic patients often have high triglyceride levels, as well as low HDL cholesterol, that make them candidates for the drugs. However, data from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial showed that fenofibrate added to statin therapy did not reduce cardiovascular events more than statins alone, and the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) also failed to show any benefit in terms of cardiovascular morbidity and mortality.

Dr. Brendan Everett (Brigham and Women’s Hospital, Boston, MA), who was not involved in the trial, praised the “well-done analysis” and provided two perspectives on the data. The first, given that dyslipidemia is rampant in the US, is that the new prescription data suggest doctors are using every tool at their disposal to reduce the risk of cardiovascular disease. That said, in light of the absence of benefit in the clinical trials, the results raise the question as to whether physicians are using those resources wisely.

“I never use fibrates,” said Everett. “I can’t remember the last time I used them. And as the investigators point out, there are very little data that they’re efficacious. The ACCORD trial is a good example of that. A diabetic population ought to be the population where they are most effective, and yet there was no benefit of using a fibrate on top of a statin. And I think that’s an important point too — a statin has to be the first drug for anybody with dyslipidemia.”

Everett said he would start a dyslipidemic patient with a high-dose statin and if the triglycerides remained high would begin treatment with niacin rather than a fibrate. Niacin has good effects on triglyceride levels, in addition to raising HDL-cholesterol levels, and there are published positive, end-point-driven trials with niacin in the statin era.

“There is a strong belief that lowering triglycerides — one aspect of the cholesterol profile in patients — would actually lower the risk of having a heart attack or the chance of dying,” said Jackevicius. “It makes sense, but unfortunately it hasn’t been demonstrated in the large studies that have been done so far.”

Jackevicius CA, Tu JV, Ross JS, et al. Use of fibrates in the United States and Canada, JAMA March 23, 2011; 305:1217-1224