Chylomicron remnants of various sizes are lowered more effectively by fenofibrate than by atorvastatin in patients with combined hyperlipidemia

Both atorvastatin and fenofibrate are known to lower postprandial chylomicrons and chylomicron remnants. However, until now it has not been investigated which of the two drugs is more effective in one and the same patient and, secondly, whether these drugs exert different effects on chylomicron remnants of different sizes. To this end 12 patients with mixed hyperlipidemia were treated in a crossover study with 40 mg atorvastatin or with 200 mg micronized fenofibrate once daily for 6 weeks. Oral fat loading was given before and after each treatment. Chylomicron remnants of various sizes were determined by fluorometric determinations of retinyl palmitate after lipoprotein separation by size-exclusion chromatography. As expected, atorvastatin was more effective than fenofibrate on total and LDL-cholesterol (P<0.05). Fenofibrate, in contrast, was more effective on all triglyceride-rich lipoproteins in both the fasting and the postprandial state. The stronger effect of fenofibrate affected not only chylomicrons and VLDL but also chylomicron remnants. It reduced large chylomicron remnants by 66% at 6 h and by 74% at 8 h. The action of atorvastatin was less pronounced, with corresponding reductions of 42 and 65% (P<0.05 only after 8 h). Fenofibrate was even more effective on small chylomicron remnants, yielding reductions of 47, 74, and 66% at 4, 6, and 8 h. Atorvastatin, in contrast, gave reductions of 30 and 26% after 6 and 8 h, the effect reaching statistical significance only after 6 h. Fenofibrate is therefore more effective than atorvastatin in lowering all triglyceride-rich lipoproteins, including large and small chylomicron remnants.