Fig. 15.1
The benefits of fenofibrate/simvastatin combination therapy in different clinical dyslipidemic patterns
Although some evidence suggests a possible heightened risk for myopathy and rhabdomyolysis [11], the combination of statin with fenofibrate is demonstrably safe, as shown in the FIELD study. However, the combination of gemfibrozil and a statin is associated with an increased risk (15-fold compared to fenofibrate) of myopathy [10, 20]. Additionally, a very recent meta-analysis [9] reported superior effects of the combination therapy compared to fibrate monotherapy, but there was an increased risk of kidney-related adverse events. Larger studies are requested to elucidate this issue, but in clinical practice physicians prescribing such co-administration should consider other potential factors known to raise the risk of myopathy (such as hypothyroidism, old age, and renal dysfunction) [26, 38].
Potential Pleiotropic Effects of Fenofibrate/Simvastatin Combination Therapy
Results of a preclinical study demonstrated that fenofibrate (50 mg/kg) and simvastatin (37.5 mg/kg) may exert neuroprotective and pleiotropic effects in experimental models of traumatic brain injury (TBI), because this combination therapy synergistically enhanced peroxisome proliferator-activated receptor (PPAR-α) activation, suggesting a prolonged and neuroprotective and antiedematous effects, decreasing the volume of post-traumatic brain lesions, compared with each drug alone that further may have an important therapeutic significance for the treatment of TBI [8].
Importantly, as it has been reviewed above, fenofibrate/simvastatin combination therapy can lead to decreased overall CV risk in patients with atherogenic lipid disorders, including those with T2DM, but patient tolerance and safety should be carefully monitored.
Conclusions
On the basis of currently available data, the co-administration of fenofibrate plus simvastatin may be recommended in the case of: (1) dyslipidemic patients who cannot take niacin (it is important to note that niacin is not available on the market in several countries) as a second-line agent if their HDL-C is <40 mg/dl and TG are >150 mg/dl; (2) mixed dyslipidemia if both TG and HDL-C are poorly controlled on statin monotherapy (except for gemfibrozil which has unacceptable risk of myopathy when used in combination with a statin); (3) mixed dyslipidemic patients who also have T2DM where combination therapy may have beneficial effects on several CV risk markers and prevent vascular complications, and, (4) patients with combined hyperlipidemia. The use of combination therapy is recommended either given simultaneously or at staggered intervals. The influence of genetic factors on apoB response to fibrate/statin therapy remains to be evaluated in further studies. However, a choice for such treatment should be individualized and supported by clinical data, based on patient tolerability and safety, and then, most importantly, carefully monitored.
Declaration of Interest
DN has participated in clinical trials sponsored by AstraZeneca and Novo Nordisk. NK has given talks, attended conferences and participated in studies sponsored by Amgen, AstraZeneca, MSD, Novartis and Novo Nordisk. PPT has given talks, attended conferences and participated in studies sponsored by Aegerion, Amarin, Amgen, GSK, Kowa, Merck, Novartis, and Sanofi-Regeneron. MB none. KAW none. KAR has given talks sponsored by AstraZeneca and Pfizer and received educational grant by Pfizer. MR has given lectures, received honoraria or research support, and participated in conferences, advisory boards and clinical trials sponsored by AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Bromatech, Chiesi Farmaceutici, Kowa, MSD Merck Sharp & Dohme, Novartis, Novo Nordisk, Rikrea and Servier. DPM has given talks, attended conferences and participated in studies sponsored by Merck, Sharp & Dohme, AstraZeneca and Genzyme.
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