Fibrates

Fibrates are agonists of the peroxisome proliferator-activated receptor alpha (PPAR-α). This activation lowers circulating triglycerides, stimulates the synthesis of Apolipoprotein A1 (ApoA1), increases the uptake of free fatty acids, enhances fatty acid oxidation, and raises HDL-C (high-density lipoprotein cholesterol).

With Gemfibrozil, a reduction in cardiovascular events of approximately 20–34% was achieved in monotherapy. Fenofibrate reduced non-fatal heart attacks by 24% in monotherapy, and by 25–28% when used as an add-on therapy in subgroups with low HDL-C and elevated triglycerides. Particularly in patients with metabolic syndrome, a 26% reduction in the risk of coronary artery disease, stroke, and cardiovascular death was observed, and in subgroups with HDL-C below 34 mg/dL and triglycerides above 204 mg/dL, the risk was reduced by as much as 36%.

Fibrates have minimal effect on LDL-C, but increase HDL-C and decrease triglycerides. Since this lipid profile is typical for patients with metabolic syndrome, fibrates show their greatest efficacy in this population. Some patients with metabolic syndrome have markedly elevated triglycerides. Triglycerides above 1000 mg/dL significantly increase the risk of pancreatitis. In such cases, combination therapy with statins and preferably micronized fenofibrate should be used.

If the fibrate is taken about 12 hours apart from the statin (rather than at the same time), there is no increased risk of rhabdomyolysis (muscle breakdown).

In the ACCORD study, adding fibrates to statins did not significantly reduce cardiovascular events overall. However, subgroup analyses suggest that patients with high triglycerides and low HDL-C did benefit from fibrate therapy. Studies confirm a reduction in triglycerides and an increase in HDL-C. A reduction in cardiovascular endpoints through fibrates appears most likely when baseline triglycerides are elevated and/or HDL-C is low before treatment.

Fibrates can be used in statin-intolerant patients or in combination with statins when target lipid levels are not achieved through statin monotherapy.

Dosage and Combination

Fibrates

The combination of fibrates and statins can increase side effects. The most feared is rhabdomyolysis (muscle breakdown). Concurrent intake of fibrates and statins should generally be avoided, as it led to an increased rate of rhabdomyolysis in the case of cerivastatin. Rhabdomyolysis often presents with muscle pain.

Well-informed patients tend to respond appropriately to symptoms, and rhabdomyolysis is very rare in such cases. Due to its low side effect profile, micronized fenofibrate 200 mg is preferred. In combination therapy, it is recommended to take fibrates in the morning and statins in the evening or vice versa.

 Statins and fibrates should not be taken at the same time!