Mixed Results with High-Dose Rosuvastatin in Subclinical Disease

June 19, 2007
Wayne Kuznar

Internal Medicine World Report, June 2007, Volume 0, Issue 0

Fenofibrate plus Statin Improves Lipid Profile in Diabetic Patients

NEW ORLEANS—The benefits of atherosclerotic regression seen in advanced disease with high-dose rosuvastatin (Crestor) are not realized in low-risk patients with subclinical atherosclerosis, but progression of their disease is halted, said John R. Crouse, III, MD, at the American College of Cardiology annual meeting.

"In studying low-risk patients without advanced disease, we may have had a limited opportunity to find regression," said Dr Crouse, in explaining the findings from a study known as METEOR (Measuring Effects on Intima-Media Thickness: An Evaluation of Rosuvastatin).

METEOR included 984 asymptomatic patients with modest thickening of the carotid intima media, an elevated level of low-density lipoprotein cholesterol (LDL-C; mean, 154 mg/dL), and a 10-year risk of coronary heart disease (CHD) of <10%, as assessed by the Framingham risk score.

"The subjects had lipid levels that currently don't require statin therapy," said Dr Crouse, professor of medicine at Wake Forest University, Winston-Salem, NC.

The patients were randomized to rosuvastatin 40 mg/day or placebo for 2 years. The primary end point was the annual rate of change in carotid intima-media thickness (CIMT) at 12 sites during the 2-year study period, as measured by B-mode ultrasound.

Although rosuvastatin significantly slowed progression of maximum CIMT when compared with placebo, significant regression of atherosclerosis did not occur in the rosuvastatin-treated patients.

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The maximum change in CIMT was -0.0014 mm/year in the rosuvastatin group and +0.0131 mm/year in the placebo group ( <.001). The change in the patients assigned to rosuvastatin was not significantly different from zero ( = .32).

It may have been optimistic to expect rosuvastatin to cause regression in low-risk patients without advanced atherosclerosis, said Dr Crouse. Nevertheless, rosuvastatin did halt progression, and the data seem to support those of ASTEROID (A Study to Evaluate the Effect of Rosuvastatin on Intravascular Ultrasound-Derived Coronary Atheroma Burden), in which high-dose rosuvastatin caused regression of atherosclerosis in high-risk patients with established CHD.

Fenofibrate&#8211;Statin Benefits

Adding fenofibrate (Tricor) to a statin results in favorable changes in a number of lipid parameters and is safe in diabetic patients with mixed dyslipidemia, according to other findings presented at the meeting.

Mixed dyslipidemia, characterized by an elevation in triglycerides, a low level of high-density lipoprotein cholesterol (HDL-C), and mildly elevated levels of LDL-C, is common in patients with diabetes, said coinvestigator Joseph B. Muhlestein, MD, director of cardiovascular research, LDS Hospital, and professor of medicine, University of Utah, Salt Lake City.

He and colleagues compared the combination of 160 mg/day of fenofibrate and 20 mg/day of simvastatin (Zocor) with either agent as monotherapy in 300 diabetic patients with dyslipidemia.

Compared with simvastatin alone (given for 12 weeks), adding fenofibrate resulted in a further 3.2% drop in LDL-C, a 52% reduction in triglycerides, a 9.5% reduction in very-low-density lipoprotein cholesterol, and a 1.2% increase in HDL-C after 9 months of therapy.

There were no cases of rhabdomyolysis, clinical myopathy, persistent myalgias, adverse hepatic events, or serious drug-related adverse events with the combination throughout the entire year of therapy.

"For a long time, the FDA recommended not to go higher than 10 mg of simvastatin when used in combination, but we showed no major adverse events with the combination of 20 mg of simvastatin and fenofibrate," said Dr Muhlestein. "It's my belief that any safe dose of a statin will also be safe with fenofibrate added on. But it's important to carefully monitor liver function and instruct patients to report muscle aches."

Fenofibrate's place in the therapy of patients with dyslipidemia is as add-on therapy. "The statin is the core, and then you work on top of it," he said.