WHAT’S NEW: We have evidence that combo therapy doesn’t further reduce risk
This study examined a previously unaddressed question, the role of combination fibrate-statin therapy in high-risk patients with type 2 diabetes. The findings do not support the routine use of combination therapy compared with a statin alone for most patients with diabetes. Overall, combination therapy with simvastatin and fenofibrate did not lower the risk of MI, stroke, or death from cardiovascular disease more than simvastatin alone.
This trial showed that women with diabetes and hyperlipidemia should not be treated with both a statin and a fibrate. Men appeared to have a very small benefit from combination therapy (NNT=50). Patients with a baseline HDL ≤34 mg/dL and baseline triglyceride ≥204 mg/dL appeared to benefit from the combination, but this group constituted only 16% of the patients in this trial and the difference had borderline statistical significance. Nonetheless, it may be reasonable to treat such patients with combination therapy until a definitive study is done.
CAVEATS: Statin dose did not match standard practice
This study used a low dose of statin. The average daily simvastatin dose was 22.3 mg in the fenofibrate-statin group and 22.4 mg in the placebo group. This constitutes low-dose therapy compared with doses routinely used in practice (ie, 40 or 80 mg). A higher dose of simvastatin may have negated any outcome differences.
CHALLENGES TO IMPLEMENTATION: This “practice changer” conflicts with NCEP guidelines
The current NCEP ATP III guidelines recommend combination fibrate-statin therapy for all patients when statin therapy alone is not adequate to achieve lipid goals. This is a major challenge to our recommendation against using this combination for most patients with diabetes. Some physicians may choose to follow the ATP III guidelines rather than the new evidence because they feel more confident adhering to national guidelines.
Clinical inertia is another challenge, as clinicians may be hesitant to stop therapy in patients already on a fibrate-statin combination. Finally, specialists may continue to use fibrate-statin combinations in all patients with diabetes who do not achieve lipid goals on a statin, and family physicians may hesitate to contradict their recommendations.
Acknowledgement
The PURLs Surveillance System is supported in part by Grant Number UL1RR024999 from the National Center for Research Resources; the grant is a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health.