Effect of fluvastatin slow-release on low density lipoprotein (LDL) subfractions in patients with type 2 diabetes mellitus: baseline LDL profile determines specific mode of action
Winkler, K.; Abletshauser, C.; Hoffmann, M.M.; Friedrich, I.; Baumstark, M.W.; Wieland, H.; März, W.
Journal of Clinical Endocrinology and Metabolism 87(12): 5485-5490
2002
ISSN/ISBN: 0021-972X PMID: 12466341 DOI: 10.1210/jc.2002-020370Document Number: 259465
The objective of this study was to determine the effect of slow-release (XL) fluvastatin on low density lipoprotein (LDL) subfractions in type 2 diabetes. A multicentre, double-blind, randomized, parallel-group comparison of fluvastatin XL 80 mg (n=42) and placebo (n=47), each given once-daily for 8 wk, in 89 patients with type 2 diabetes (HbA1c: 7.2+or-1.0%, LDL cholesterol (LDL-C): 3.4+or-0.7 mmol/litre, high density lipoprotein cholesterol: 1.1+or-0.3 mmol/litre, and triglycerides (TG): 2.4+or-1.4 mmol/litre). At baseline and on treatment, plasma lipoproteins were isolated and quantified. Eight weeks of fluvastatin treatment decreased total cholesterol (-23.0%, P<0.001), LDL-C (-29%, P<0.001) and TG (-18%, P< 0.001), compared with placebo. At baseline, there was a preponderance of dense LDL (dLDL) (apolipoprotein B in LDL-5 plus LDL-6>25 mg/dl) in 79% of patients, among whom fluvastatin decreased all LDL subfractions, reductions in dLDL being greatest (-28%, P=0.001; cholesterol in dLDL -29%). In patients with low baseline dLDL (apolipoprotein B in LDL-5 plus LDL-6<=25 mg/dl), but a preponderance of buoyant LDL (LDL-1 through LDL-3), fluvastatin significantly decreased only these subfractions. Fluvastatin 80 mg XL, once daily, decreased total cholesterol and total LDL-C. In patients with atherogenic dLDL, absolute changes of dLDL were most pronounced, emphasizing the value of fluvastatin treatment in type 2 diabetes. The antiatherogenic potential of fluvastatin in type 2 diabetes may thus be greater than that expected from its effects on LDL-C and TG alone.