Postprandial lipemia is known to exert a reversible detrimental effect on endothelium-dependent flow-mediated vasodilation (FMD). Fasting FMD has shown to be improved by fluvastatin. In this study, we investigated whether lipemia-induced endothelial dysfunction can be mitigated by fluvastatin in two (immediate-release and extended-release) formulations.
In 27 patients with the metabolic syndrome, randomized in a three-period crossover design for 5 weeks each to 80 mg extended-release fluvastatin daily, 40 mg immediate-release fluvastatin twice daily (b.i.d.) or placebo, the fasting and postprandial lipids and FMD of the brachial artery were measured at baseline and after 5 weeks of each treatment period. Postprandial lipemia was induced by administration of whipping cream containing 33% fat (1 g fat/kg body weight). FMD was determined by two-dimensional ultrasonography of the brachial artery in the fasting state and 4 h after the fatty meal. Lipids were determined using routine methods.
Fasting triglycerides were reduced after immediate-release and extended-release fluvastatin by 16 and 23%, respectively, and postprandial triglycerides by 20 and 29%, respectively. The fasting FMD was also improved by each treatment. The postprandial FMD impairment, however, was mitigated only after 40 mg b.i.d. After 80 mg fluvastatin, the last dose of which had been administered the previous evening, the lipemic FMD impairment was the same as after the placebo.
Fluvastatin improves fasting FMD regardless of whether it is administered as 40 mg b.i.d. or 80 mg daily given in the evening. The lipemic FMD impairment, in contrast, is improved only by 40 mg b.i.d. when the tablet is taken in the morning of the test day. As the half-life of fluvastatin is about 2 h, we surmise that an improvement occurs only when sufficient amounts of fluvastatin are present in the bloodstream.