Tag Archives: Fibrate

Diabetes Management: Tight Cholesterol, BP Control Does Little Good for Diabetics

Lower isn’t always better in diabetes management. In fact, pushing too hard may not help, and may actually hurt in some cases. This has been proved, once again, by the landmark Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial, results released last week reveal. Indeed, the new lipid and blood pressure results round out the negative portrait of aggressive risk factor management in diabetes patients.

(ACCORD is one of the largest studies ever conducted in adults with type 2 diabetes who were at especially high risk of cardiovascular events, such as heart attacks, stroke, or death from cardiovascular disease.  The multicenter 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 high density lipoprotein (HDL) cholesterol and triglycerides, in addition to standard therapy of lowering low density lipoprotein (LDL) cholesterol. Read the Questions & Answers about the ACCORD Trial here.)

According to received wisdom, intensive blood pressure and blood fat management could drive down diabetics’ higher risks of heart problems. But results from the ACCORD trial prove that when it comes to traditional measurements of heart disease risk, a blood pressure target of 120 mm Hg rather than the general population standard of 140 did not reduce nonfatal heart attacks, nonfatal strokes or death from cardiovascular causes.

Likewise, adding the cholesterol-busting drug fenofibrate to standard statin therapy did not reduce the chances of major adverse cardiovascular events. Indeed, tribal behavior by physicians that is no doubt driven by the big pharma marketing machinery, has raised concerns about the ramifications of recommending costly medications that don’t confer real benefits to patients. (See my post ‘Increased Use of Fibrates in US Could Be A Triumph Of Marketing Over Medicine’ here.)

Both studies ‒ part of the complex ACCORD trial ‒ were presented at the American College of Cardiology meeting in Atlanta, Ga. and released simultaneously online in the New England Journal of Medicine.

[A third part of this research ‒ one which examined intensive lowering of blood sugar to see if this had a positive effect ‒ was prematurely halted in 2008 because it turned out that patients receiving this approach actually had an increased, instead of decreased, risk of death. (See a related post ‘Aggressive Diabetes Therapy May Raise Death Risk’ here.)]

As for the newly released findings, the lipid arm of ACCORD included 5,518 patients with high risk of heart problems because of cardiovascular disease or at least two risk factors. LDL, or bad, cholesterol levels had to be between 60 and 180 mg/dL; HDL, or good cholesterol, levels had to be under 50 mg/dL or 55 mg/dL for women and blacks; and triglycerides had to be under 750 mg/dL if the patients were not on any therapy, or 400 mg/dL otherwise. Patients either received fenofibrate or a placebo in addition to statins.

What the researchers found was that lipid and triglyceride levels responded as expected. Despite this, however, the patients appeared to receive no benefit when it came to major heart problems such as heart failure, stroke and nonfatal heart attacks.

Meanwhile, the  blood pressure portion of ACCORD compared a strategy of keeping systolic blood pressure under 120 mm Hg to one of under 140 mm Hg in 4,733 diabetes patients with high risk of cardiovascular events because of clinical or subclinical heart disease or at least two risk factors. In this trial, treatment effectively lowered blood pressure. But again, there was no impact on aspects of patient health including death risk, death related to heart problems and nonfatal heart attacks.

ABC News reported that the U.S. Food and Drug Administration will conduct a full review of findings from the ACCORD study. An FDA spokesperson said the agency planned to include a review of the labeling and indications for fenofibric acid (Trilipix) ‒ even though the trial used fenobrate (TriCor). Asked about the timing of the announcement, the spokesperson said the FDA was attempting to be more proactive.

Both Trilipix and TriCor are marketed by Abbott, and Trilipix is “the active metabolite of TriCor,” according to Dr. Marshall Elam of the Memphis VA Medical Center. Elam, who was involved in the design of the lipid treatment arm of ACCORD said that “neither TriCor nor Trilipix has a label indication for cardiovascular disease.”

In a statement released after the ACCORD results were reported, but before the FDA said it would conduct a review of the ACCORD findings, Abbott said the data from the ACCORD Lipid trial “supports the appropriate patient type and current treatment guidelines for fibrates. The top-line results of the study were widely expected, given that two-thirds of patients in the trial would not be recommended for fibrate therapy under current guidelines.”


Diabetes: Increased Use of Fibrates in US Could Be A Triumph Of ‘Marketing Over Medicine’

U.S. prescriptions for cholesterol-lowering medications predating statins have increased steadily despite uncertain benefit, suggesting that aggressive marketing has trumped scientific evidence.

These drugs, called fibrates, modestly reduce blood levels of artery-clogging bad cholesterol, raise good cholesterol and are most effective at lowering levels of other damaging blood fats called triglycerides, although the overall picture from clinical trials remains confusing.

Fibrates include gemfibrozil (Lopid), which got the regulatory nod in 1981; fenofibrate (TriCor, Triglide), approved in 2007, and the closely related drug fenofibric acid (TriLipix, Fibricor), which entered the U.S. pharmaceutical marketplace in December 2008. In 2009, fenofibrate and fenofibric acid together accounted for almost 74 percent of the U.S. market share of fibrates.

According to Dr. Cam Patterson, cardiology chief and physician-in-chief of the Center for Heart and Vascular Care at the University of North Carolina, Chapel Hill, “Statins are the only cholesterol-lowering drugs that have been shown conclusively to save lives. Fibrates may be an option as add-on therapy, but there is no compelling case to use them as first-line therapy” for patients with elevated cholesterol, he warns.

Patterson feels the substantial increase in fibrate use demonstrated “unfortunate tribal behavior by physicians that is no doubt driven by the big pharma marketing machinery” and expressed concern about the ramifications of “recommending costly medications that don’t confer real benefits to our patients. We’ve been burned before.”

“The use of fibrates in America is very troubling,” says Dr. Steven E. Nissen, chairman of cardiovascular medicine at the Cleveland Clinic Foundation. Describing the increasing use of fibrates as an expensive failure to educate doctors and regulators, he notes that fibrates are among medications advertised directly to consumers. “This is a classical example of marketing triumphing over science,” he feels.

Dr. James H. Stein, director of preventive cardiology at the University of Wisconsin-Madison School of Medicine and Public Health, says most people don’t realize the influence of marketing on health care. Pointing out that negative studies about fibrates have been “spun to focus on the possible benefits”, he cautions that fenofibrate is associated with significant side effects, including “increased creatinine, which might indicate kidney dysfunction; gallstones, and more serious complications like pancreatitis, blood clots, and pulmonary embolism.”

In the past five years, two major studies have found fenofibrate failed to reduce heart disease risks among diabetic men and women. Last year, the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial, which involved 10,000 patients with diabetes, found that those who took both simvastatin and fenofibrate suffered about as many heart attacks, strokes and deaths as diabetic patients treated with simvastatin alone.

The Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) trial, which involved nearly 10,000 patients and has reported results since 2005, found that fenofibrate failed to decrease cardiovascular deaths more than a placebo.

Yet a new study published in the current issue of the Journal of the American Medical Association found that U.S. prescriptions for fibrates grew from 336 per 100,000 people in January 2002, to 730 per 100,000 people in December 2009. That’s a 117.1 percent hike. At the same time, Canadian prescriptions for fibrates held nearly steady, at 402 per 100,000 in early 2002 and 474 per 100,000 in late 2009.

The increase in fibrate prescriptions, driven by a 200 percent jump in the use of fenofibrate, has outpaced the growth of statins. But, to keep things in perspective: statins, which are among the most commonly prescribed medications, remain blockbuster drugs that dominate lipid-lowering treatment, with fibrates accounting for just 9.4 percent of the U.S. lipid-lowering market in 2009.

Based on a news report in ABC News

Two Therapies May Slow Diabetic Retinopathy in Type 2 Diabetes

In high-risk adults with Type 2 diabetes, researchers have found that two therapies may slow the progression of diabetic retinopathy, an eye disease that is the leading cause of vision loss in diabetics.

Intensive blood-sugar control reduced the progression of diabetic retinopathy, compared with standard blood-sugar control, and combination lipid therapy with a fibrate and statin also reduced disease progression, compared with statin therapy alone. However, intensive blood pressure control provided no additional benefit to patients compared with standard blood pressure control.

Results of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) Eye Study, supported by the National Institutes of Health, recently were published in the New England Journal of Medicine and presented at the 70th Scientific Sessions of the American Diabetes Association.

“This is the largest study to date examining the effects of blood sugar, combination lipid therapy, and blood pressure control on the prevention of diabetic retinopathy progression using retinal photographs,” stated Walter Ambrosius, a professor of biostatistical sciences in the Division of Public Health Sciences at Wake Forest University Baptist Medical Center and principal investigator of the ACCORD Eye study’s coordinating center, in a July 23 release.

“Many people with diabetes have microvascular problems, which can result in problems with the kidneys and amputation of toes and feet, and the only place that you can directly observe the microvasculature is in the back of the eyes. What we have seen in the eyes is potentially an indicator of what is happening in other parts of the body.”

“The ACCORD Eye Study clearly indicates that intensive glycemic control and fibrate treatment added to statin therapy separately reduce the progression of diabetic retinopathy,” added Emily Chew, chair of the Eye Study and chief of the Clinical Trials Branch of the Division of Epidemiology and Clinical Applications at the National Eye Institute.

“The main ACCORD findings showed that fibrate treatment added to statin therapy is safe for patients like those involved in the study. However, intensive blood sugar control to near normal glucose levels increased the risk of death and severe low blood sugar, so patients and their doctors must take these potential risks into account when implementing a diabetes treatment plan.”

The ACCORD study was a landmark clinical trial that included 10,251 adults with Type 2 diabetes who were at especially high risk for heart attack, stroke or cardiovascular death. The study evaluated three intensive strategies, compared with standard treatments for lowering cardiovascular risks associated with diabetes.
Michael Johnsen/DrugStore News

%d bloggers like this: