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Better efficacy, safety demonstrated by atorvastatin, fenofibrate fixed-dose combination relative to monotherapies

Sunday, November 16 2008 | Comments

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What's This? By Patrice La Vigne

Combination fixed-dose therapy with atorvastatin and low-dose fenofibrate may lead to greater improvements in lipid parameters relative to atorvastatin or fenofibrate alone, new evidence shows.

In the multicenter, double-blind study, 220 patients (mean age, 55.9 years) with mixed dyslipidemia were randomized to 3 arms--40 mg of atorvastatin plus 100 mg of fenofibrate (n=73), 40 mg of atorvastatin monotherapy (n=74), or 145 mg of fenofibrate monotherapy (n=73)--for 12 weeks. In total, 26.3% were using prior lipid-altering drugs.

Levels of total cholesterol minus high-density lipoprotein (HDL) cholesterol fell by 44.8% to a final average of 114.4 mg/dL in the combination group and by 40.2% in the atorvastatin monotherapy group to a final average of 125.8 mg/dL (P=.074). These levels only fell by 16.1% to an average of 175.7 mg/dL in the fenofibrate monotherapy cohort compared with the combination cohort (P<.001).

HDL cholesterol levels rose by 19.7% to a mean of 51.3 mg/dL in the combination group and by 6.5% to a mean of 44.4 mg/dL in the atorvastatin group (P<.001). In the fenofibrate group, HDL levels increased by 18.2% to 48.4 mg/dL, which did not significantly differ from combination therapy.

Triglyceride levels decreased by 49.1% to a mean of 123.8 mg/dL in the combination group, by 28.9% to 173.7 mg/dL in the atorvastatin monotherapy group (P<.001), and by 27.8% to 157.2 mg/dL in the fenofibrate monotherapy group (P=.001).

In terms of secondary variables, the combination therapy led to greater decreases in apolipoprotein B as compared with atorvastatin monotherapy (-40.5% vs -35.7%; P=.046) or fenofibrate monotherapy (-40.5% vs -14.9%; P<.001). Low-density lipoprotein cholesterol levels decreased by 42.3% in the combination cohort, 43.1% in the atorvastatin monotherapy cohort, and 13.9% in the fenofibrate monotherapy group, with the difference between the combination treatment and fenofibrate monotherapy being statistically significant (P<.001).
 
The results also showed an improvement in safety with the use of the combination tablet relative to the individual therapies. The overall incidence of adverse events was 58.9%, 66.2%, and 65.8% for the 3 respective groups. Furthermore, the combination therapy had the fewest related adverse events (16.4%).

Study researcher Herman Griffin from LifeCycle Pharma Inc. in New York City told VerusMed that the market for co-administered statin-fibrate therapies is already increasing and is going to increase more.

"If you look at patients who are on statins and may or may not be reaching their targets--triglyceride levels, LDL cholesterol levels--adding another statin typically does not do the trick," he told VerusMed. "You really need something else at that point."

He noted that fenofibrate is one of the monotherapies being targeted for combination therapy. Since the current study ended in April, some patients have continued in a 12-month open-label extension study and he said those results should be out in the second quarter of 2009. (Abstract Poster Session 5069.)

LifeCycle sponsored the study.

This information concerns a use that has not been approved by the Food and Drug Administration.

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